Surface Functionalization of Biomaterials by Radical Polymerization ⇑ ⇑ Tian Zhou A, Yizhou Zhu A, Xia Li A, Xiangmei Liu A, , Kelvin W.K

Progress in Materials Science 83 (2016) 191–235

Contents lists available at ScienceDirect

Progress in Materials Science

journal homepage: www.elsevier.com/locate/pmatsci

Surface functionalization of biomaterials by radical polymerization ⇑ ⇑ Tian Zhou a, Yizhou Zhu a, Xia Li a, Xiangmei Liu a, , Kelvin W.K. Yeung b, Shuilin Wu a, , Xianbao Wang a, Zhenduo Cui c, Xianjin Yang c, Paul K. Chu d a Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, School of Materials Science & Engineering, Hubei University, Wuhan 430062, China b Division of Spine Surgery, Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 999077, Hong Kong, China c School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China d Department of Physics & Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China article info abstract

Article history: One effective strategy in the ﬁeld of biomaterials is to develop biomimetic interfaces to Received 28 December 2015 modulate the cell behavior and promote tissue regeneration and surface modiﬁcation is Received in revised form 21 March 2016 the best way to obtain biomaterial surfaces with the desired biological functions and Accepted 23 April 2016 properties. Surface radical polymerization offers many advantages compared to other Available online 23 April 2016 methods, for instance, low cost and simplicity, ability to control the surface chemistry without changing the properties of the bulk materials by introducing high-density graft Keywords: chains and precisely controlling the location of the chains grafted to the surface, as well Surface functionalization as long-term chemical stability of the chains introduced by this method due to the covalent Polymerization Surface chemistry bonding. Because of the precise control of the macromolecules and easy preparation, con- Biomaterials trolled/living radical polymerization has been widely used to modify biomaterials. There Tissue engineering are three main techniques: atom transfer radical polymerization (ATRP), nitroxide- Biomimetic mediated polymerization (NMP), and reversible radical addition-fragmentation chain transfer (RAFT) polymerization. Some other grafting methods such as plasma-induced polymerization, irradiation-induced polymerization, and photo-induced polymerization also have great potential pertaining to functionalization of biomaterials and tailoring of surface chemistry. This paper summarizes recent advances in the various grafting polymerization methods to enhance the surface properties and biological functions of biomaterials. Ó 2016 Elsevier Ltd. All rights reserved.

Contents

1. Introduction ...... 192 1.1. Necessity for surface modification for biomaterials ...... 192 1.2. General background on grafting polymerization...... 192 1.2.1. ‘‘Grafting to” and ‘‘grafting from” approaches ...... 192 1.2.2. Controlled/living radical polymerization...... 193 1.2.3. Brief introduction of other grafting methods ...... 194 2. Nitroxide-mediated polymerization ...... 194

⇑ Corresponding authors. E-mail addresses: [email protected] (X. Liu), [email protected], [email protected] (S. Wu). http://dx.doi.org/10.1016/j.pmatsci.2016.04.005 0079-6425/Ó 2016 Elsevier Ltd. All rights reserved. 192 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

2.1. Fundamentals of NMP...... 194 2.2. Surface grafting of biomaterials by SI-NMP...... 194 2.2.1. Biometals ...... 195 2.2.2. Bioceramics ...... 195 2.2.3. Biopolymers ...... 198 2.2.4. Others ...... 198 2.3. ‘‘Grafting to” route ...... 200 2.4. Factors influencing the properties of polymerized films by NMP ...... 200 3. Atom transfer radical polymerization ...... 201 3.1. Fundamentals of ATRP ...... 201 3.2. Surface grafting of biomaterials by ATRP...... 201 3.2.1. Functionalized surface coatings ...... 201 3.2.2. Factors influencing the properties of polymerized films by ATRP...... 206 4. Reversible addition-fragmentation chain transfer polymerization ...... 206 4.1. Fundamentals of RAFT polymerization ...... 207 4.2. Surface polymerization of biomaterials by RAFT...... 208 4.2.1. Monomers used in RAFT polymerization ...... 208 4.2.2. Factors influencing the properties of polymerized films by RAFT ...... 209 5. Other surface radical polymerization methods ...... 211 5.1. Plasma-induced radical polymerization...... 211 5.2. Radiation-induced radical polymerization...... 213 5.3. Photo-induced radical polymerization ...... 215 6. Biocompatibility of polymerized surfaces...... 223 6.1. Cytotoxicity ...... 223 6.2. Hemocompatibility ...... 223 6.3. Manipulation of cell behaviors ...... 224 7. Conclusion and outlook ...... 225 Acknowledgements ...... 226 References ...... 226

1. Introduction

1.1. Necessity for surface modiﬁcation for biomaterials

Biomaterials are widely used in biomedical devices or biological products in clinical biological diagnosis, treatment/ repair, replacement of damaged tissues and organs, and enhancement of functions [1,2]. However, some interactions between the biomaterials and biological tissues may undermine the ability of these materials to carry out their designed biological functions sometimes even producing adverse effects. For instance, the contact between synthetic implants and blood often leads to protein adsorption, platelet adhesion, and concomitant activation of the body’s defense system, consequently inducing thrombosis and pulmonary thromboembolism [3–6]. Post-operative implant-related bacterial infection has been reported to result in implant failure in 2%, 5% and 14% of implants for bone fracture fixation, total hip replacement, and knee replacement, respectively [7–9]. Hence, a suitable surface design is crucial to more successful application of biomaterials because surfaces are in direct contact with the biological media [10]. Before biological events take place in response to the biomaterials, cells detect the surface affinity through the recognization of the filopodia of cellular transmembrane proteins. Many studies confirm that both the surface structure and surface chemistry influence the initial cell behavior such as adhesion, migration, proliferation, and differentiation on biomaterials [11–13]. It is important to perform surface functionalization to endow currently available biomaterials with specific and desirable functions. Currently, surface modification can be used to modulate the surface properties of substrates such as adhesion, wettability, biocompatibility, and antifouling [7–9,14]. Radical polymerization as one of surface modification methods is particularly useful because it can easily and controllably introduce high-density graft chains and graft them in a precise manner without affecting the original properties of substrates [15]. Moreover, covalent attachment of graft chains onto the surface can minimize chain delamination improving the long-term chemical stability of the introduced chains and it is possible to graft different polymers onto the same substrate [16].

1.2. General background on grafting polymerization

1.2.1. ‘‘Grafting to” and ‘‘grafting from” approaches Polymers can be grafted onto the surface to produce functional polymer brushes to tailor the surface properties and there are two general ways to prepare polymer brushes: physisorption and covalent attachment [17–19]. Polymer physisorption is a reversible process in which the polymer chains with the sticking segments adsorb onto a suitable substrate but such polymer brushes are often unstable. Stamm et al. reported that poly(N-isopropylacrylamide) (NIPAM) brushes were T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 193 immobilized with gold nanoparticles by physisorption [20] and covalent attachment could be accomplished by either the ‘‘grafting to” or ‘‘grafting from” approaches [17,21]. In the ‘‘grafting to” approach, the polymer chains are bonded by the reactions between those preformed, end- functionalized polymers and the reactive groups on the substrate. Although this method was widely used in the early days due to the simplicity [22–25], there is a significant drawback that only a small amount of the polymer can be immobilized on the surface due to steric constraints and kinetic factors [26,27]. The space constraints around potential reactive sites further limit the grafting density and this barrier becomes greater when the layer thickness increases. Hence, the ‘‘grafting-to” method generally results in brushes with small grafting densities and film thicknesses [26]. The ‘‘grafting from” approach, also referred to as surface-initiated polymerization, utilizes the initiators bound to the substrate to initiate polymerization and the polymer evolves from the surface itself. This technique provides a viable alternative to control the functionality, density, and thickness of the polymer brushes [18]. Owing to the effectiveness in producing thick and large-density functional polymer brushes in a controllable fashion [19], the ‘‘grafting from” approach has attracted much interest in recent years [26,28,29]. In fact, the ‘‘grafting from” and ‘‘grafting to” techniques can be implemented together [30]. For instance, Berger reported that the first polymer could be immobilized onto one side of silica particles using the ‘‘grafting from” approach and the second polymer was grafted onto the other side of the particle surface via the ‘‘grafting to” approach [30].

1.2.2. Controlled/living radical polymerization Grafting methods can be classiﬁed according to the type of radical bonding in traditional radical polymerization, ionic and ring-opening polymerization, and controlled/living radical polymerization (CLRP). The major drawback of conventional radical polymerization is the lack of control of the polymer structure [31,32], while ionic polymerization requires demanding conditions such as very low temperature without moisture. Furthermore, only a limited number of monomers can be used to trigger undesirable side reactions due to the presence of functional groups in the monomers. In contrast, CLRP is a simple process that produces well-deﬁned, low-polydispersity, and multi-functional polymers [33–38] and the polymer architecture can be precisely controlled [39–42]. CLRP usually includes three categories: atom transfer radical polymerization (ATRP), nitroxide-mediated polymerization (NMP), and reversible radical addition-fragmentation chain transfer (RAFT) polymerization, which will be discussed individually in details later in this review.

1.2.2.1. Fundamentals of CLRP. The general reaction in CLRP is illustrated in Fig. 1 [41]. The key feature of all CLRP systems is the establishment of a dynamic equilibrium between propagating radicals P and various dormant species throughout the polymerization process to minimize the occurrence of irreversible termination reactions [43]. The dormant (end-capped) chain P–X can be activated to produce the polymer radical P by thermal, photochemical, and/or chemical stimuli. If the monomer M is present, P will undergo propagation until it is deactivated back to P–X. Generally, [P]/[P–X] should be less than 105 to ensure the success of the reaction, indicating that a living chain spends most of the polymerization time in the dormant state.

1.2.2.2. Architecture of polymers grafted onto the surface. When the surface of biomaterials is grafted with polymers by CLRP, the polymeric architecture is very important. According to the topography of the polymers, the polymeric structures include star polymers, comb polymers, hyperbranched polymers, network and cyclic polymers. Star polymers possess lower bulk and solution viscosities as well as many chain-end functionalities compared to linear polymers. Star polymers are usually prepared by two different routes: the ‘‘core-first” approach and ‘‘arm-first” approach that are suitable for ATRP, NMP and RAFT polymerization [40]. Since the ‘‘core-first” approach employs multifunctional initiators from which several arms are grown simultaneously, ATRP is more useful for polyols that can be converted to an initiating core with more initiating sites [44].In the ‘‘arm-first” approach, the polymer chains are attached to a functional core. RAFT polymerization offers a unique possibility since the RAFT reagents can be attached to a core via the Z group [45]. Comb polymers have a main polymer chain and side chains with the same chemical nature. Yu et al. prepared well- defined comb copolymer brushes on poly(tetrafluoroethylene) (PTFE) films by surface-initiated CLRP [46]. The poly(glycidyl methacrylate) (PGMA) brushes were synthesized on the pretreated PTFE film by surface-initiated RAFT polymerization and the hydrophilic vinyl monomers sodium salt of 4-styrenesulfonic acid (NaSS) was polymerized on the epoxy groups side chains of the PGMA brushes by surface-initiated ATRP. Hyperbranched polymers are polymers with a dense and branched structure and a large number of end-groups, which are also called dendritic polymers. Mori and co-workers prepared hyperbranched polymers from silicon by self-condensing ATRP [47,48] and one-pot hyperbranched polymers was synthesized by RAFT [49].

Fig. 1. The mechanism of controlled/living radical polymerization (CLRP) [41]. Copyright 2007. Adapted with permission from Elsevier Science Ltd. 194 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

Polymer networks have attracted significant interest due to the well-defined mechanical and physical properties [50,51]. Microgel networks can be formed by preparing well-defined polymers with crosslinkable pendant moieties. Oh et al. prepared cross-linked nanogel with a uniformly cross-linked network utilizing ATRP and it was possible to use crosslinkers which could be reversibly cleaved to form reversible gels [52]. The traditional way to prepare cyclic structures is based on intramolecular cyclization of a linear precursor of the cyclic polymer and either two identical or two different functional groups react with each other. For example, Lepoittevin et al. prepared macrocyclic polystyrenes with controlled dimensions and narrow distributions via CLRP [53].

1.2.3. Brief introduction of other grafting methods In addition to the aforementioned surface grafting methods, three polymerization techniques have been developed to improve the surface properties of biomaterials, plasma-induced graft polymerization, radiation-induced graft polymerization and photo-induced graft polymerization. For example, biomedical stainless steel, titanium alloy, polystyrene (PS), polycaprolactone (PCL), polyethylene (PE), polypropylene (PP), and polymethyl methacrylate (PMMA) are often modiﬁed by these grafting methods.

2. Nitroxide-mediated polymerization

NMP is the simplest CLRP technique by just adding free nitroxides in the conventional radical polymerization process. In comparison with other CLRP methods, NMP is purely thermal activation that does not require any catalyst or bimolecular exchange. In addition, it does not require puriﬁcation after polymerization and aqueous processes can be implemented because the reagents in NMP are typically environmentally friendly [32,54].

2.1. Fundamentals of NMP

NMP involves a reversible activation–deactivation equilibrium in which nitroxide acting as a control agent reversibly deactivates the propagating and growing radicals to an alkoxyamine dormant end-functionality as the predominant species (Fig. 2) [55]. Whenever this equilibrium is turned to the dormant form, the irreversible chain termination is limited and the stationary concentration of the active species is small. NMP can be initiated in two different ways. The first is the bicomponent initiating system consisting of a conventional thermal initiator (e.g., 2,20-azobisisobutyronitrile (AIBN) or benzoyl peroxide (BPO)) and a stable free nitroxide (e.g., 2,2,6, 6-tetramethylpiperidinyloxy (TEMPO)) [56]. When these systems are used, conventional radical polymerization can be employed in the NMP process by simply adding free nitroxides. However, this system cannot accurately define the structure and concentration of the initiating species. In contrast, in the monocomponent initiating system, the well-defined unimolecular initiator can release both the initiating radical and nitroxide with a 1/1 M ratio by thermolysis to circumvent this problem [57–59].

As shown in Fig. 2, it is predicted theoretically that the activation–deactivation equilibrium (equilibrium constant K = kd/ kc) and persistent radical effect (PRE) control the polymerization kinetics in NMP [60]. Practically, side reactions significantly affect the polymerization rate in some cases. The first one involves the presence of an excess of free nitroxide when the reacted monomers (e.g., acrylates) have a high propagation rate constant (kp). It leads to rapid consumption of the initiating alkoxyamine resulting in living polymer chains with poor control. The second factor is degradation of nitroxides. Nitroxides are only highly effective at a relatively low temperature and degrade at temperature over 120 °C in NMP. The potential application of unstable nitroxides depends on the nature of the degradation products. The third way to influence the polymerization rate is to use additional long half-life radical initiators to decrease the concentration of the free nitroxide in the medium. The most complex side reaction in NMP is disproportionation or the hydrogen transfer reaction [61,62].

2.2. Surface grafting of biomaterials by SI-NMP

NMP can be used to modify biomaterials by introducing bioactive polymeric groups to the surface regardless of the nature of the substrates. Owing to the living nature of NMP, this method can be applied to surface-initiated polymerization and ‘‘grafting to” processes [63]. The former requires a well-deﬁned initiator and controlled chain growth, whereas the latter requires the ability to end-functionalize the chains. In surface-initiated NMP (SI-NMP), binding of the initiator depends

Fig. 2. The mechanism of nitroxide-mediated polymerization (NMP) [55]. Copyright 2008. Adapted with permission from the American Chemical Society. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 195 on the chemical nature of the inorganic surface and can take place via covalent bonding, electrostatic interaction, or hydrogen bonding. In the second case, NMP-derived copolymers are grown on the surface of the inorganic substrate by covalently bonding with reactive groups. However, on account of steric hindrance, the ‘‘grafting to” process generally produces in brushes with small grafting density and ﬁlm thickness. Hence, this method is not very popular.

2.2.1. Biometals Owing to excellent mechanical properties such as high strength, toughness, wear resistance, and corrosion resistance, metals are often used in biomedical devices and orthopedic implants [64]. Recently, biodegradable metals such as Mg- based alloys, Fe-based alloys, and Zn-based alloys are popular in tissue regeneration applications such as intravascular stents and bone scaffolds [65]. However, the bioinert nature of some metals and antibacterial performance must be improved. Ignatova and co-workers utilized a two-step ‘‘grafting-from” method to synthesize copolymer brushes on stainless steel. Electrografting of the poly(2-phenyl-2-(2,2,6,6-tetramethyl-piperidin-1-yloxy)-ethylacrylate) with a large grafting density was conduced as the initiator (first step) followed by nitroxide-mediated radical polymerization of 2-(dimethylamino ethyl)acrylate and styrene or n-butyl acrylate (second step) initiated by the electrografted polyacrylate chains [66]. The process is schematically illustrated in Fig. 3 [66]. The functionalized surface exhibited significant antibacterial activity against the Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli) and the antibacterial activity decreased when the alkyl chain length increased. Furthermore, the thickness and hydrophilicity of the adherent copolymer films could be adjusted by SI-NMP [66]. A similar process was implemented in the synthesis of copolymer brushes on a steel surface on which acrylate was first electropolymerized under a cathodic potential and NMP of styrene was initiated from the electrografted polyacrylate chains with formation of polystyrene with a controlled molecular weight and narrow polydispersity [67].

2.2.2. Bioceramics Owing to the excellent biocompatibility, bioceramics are popular in tissue repair, maintenance, and restoration to improve the functions of organs and tissues [68]. For example, the excellent properties of silica nanoparticles such as the high intrinsic tunable porosity, hydroxyl surface functionality, and specific surface area make the materials suitable for NMP [69], especially SI-NMP in applications including drug delivery, drug discovery and biosensing [68,70–73]. Bartholome and co-workers prepared PS-grafted silica particles by simple condensation and reacted these particles with a nitroxide/conventional radical initiator (e.g., AIBN or BPO) bicomponent system [74]. The modified silica particles exhibited better colloidal stability and enhanced dispersibility in toluene. Chevigny et al. proposed a new convenient and efficient SI- NMP method using a covalent grafting strategy involving an alkoxyamine which acted both as the initiator and controller agent [75]. The synthesis parameters were optimized to obtain good conversion rates and expected molecular weight of the grafted chains while maintaining the colloidal stability and avoiding aggregation of silica particles. The synthetic and characterization methods represented a robust and reproducible way to design well-defined grafted polymer nanoparticles. Subsequently, this group synthesized well-defined PS-grafted silica nanoparticles by adapting their previous synthetic process without using a free initiator to tune the grafted chains while controlling polymerization and colloidal stability while avoiding the formation of free polymer chains [76]. Recently, Zhao et al. prepared poly(tert-butyl acrylate) (PtBA)/PS brushes on silica nanoparticles by sequential ATRP of tert-butyl acrylate (tBA) at 75 °C and NMP of styrene at 120 °C [77–80]. Subsequent hydrolysis of the tert-butyl groups produced amphiphilic mixed poly(acrylic acid) (PAA)/PS brushes that underwent chain reorganization in response to environmental changes [77]. The mixed PtBA/PS brushes exhibited two distinct glass transition temperatures, suggesting that the two grafted polymers were microphase-separated in the brush layer (Fig. 4) [78,79]. The grafting density increased from 0.6–0.7 chains nm2 to 0.9–1.2 chains nm2 when a triethoxysilane anchoring group was used instead of a chlorodimethylsilane group [79]. Later, this group studied the effects of the overall grafting density on the microphase separation of PtBA/PS brushes [80]. A series of mixed PtBA/PS brushes with different overall grafting densities but similar molecular weights and comparable individual grafting densities for the two polymers was prepared by changing the mass ratio of the Y-initiator to silica particles in the initiator immobilization step (Fig. 5) [80]. When the grafting density was further

Fig. 3. Two-step ‘‘grafting from” strategy by electrochemistry [66]. Copyright 2004. Adapted with permission from the American Chemical Society. 196 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

Fig. 4. Schematic illustration of phase morphologies of mixed PtBA/PS brushes with a ﬁxed PtBA molecular weight and varying PS molecular weight [78]. Copyright 2010. Adapted with permission from the American Chemical Society.

Fig. 5. Synthesis of mixed homopolymer brushes with various overall grafting densities by changing the mass ratio of Y-initiator to silica particles in the initiator immobilization step via an ammonia-catalyzed hydrolysis/condensation process [80]. Copyright 2012. Adapted with permission from the American Chemical Society.

decreased, phase separation became weaker and no microphase separation was observed from the sample with an overall grafting density of 0.122 chain/nm2. The properties of the materials were related to microphase separation. Recent research has demonstrated that mesoporous silica particles can be used as NMP substrates [81]. Although SI-NMP of styrene was performed from various types of ordered mesoporous silica particles with different morphologies and pore sizes, the pore diameter was critical to diffusion of the chemical agents. For instance, a diameter of 2 nm was too small to ensure good diffusion of the reagents and 5 nm was adequate. The pore morphology and connectivity were crucial to diffusion of the chemical agents when the pores were larger than 5 nm [81].

TiO2-based nanostructured materials play important roles in many biomedical applications such as tissue reconstruction and disease diagnosis due to their excellent biocompatibility, good chemical stability, high catalytic efficiency, excellent mechanical properties, and high strength-to-weight ratio [82]. Some properties can be enhanced by surface grafting high-density PS brushes onto the surfaces by SI-NMP [83,84]. For example, PS-grafted-TiO2 hybrid films exhibited high trans- mittance in the visible light region together with the ultraviolet absorption characteristics of TiO2 because PS-grafted-TiO2 nanoparticles formed a stable dispersion in good solvents for the PS chains [83]. In addition, the PS hybrid films with

PS-grafted-TiO2 showed enhanced wear resistance compared to the PS ﬁlm, possibly because the PS-grafted-TiO2 nanoparticles at the interface between the silicon wafer surface and PS thin ﬁlm withstood the load [83,84]. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 197

Fe3O4 nanoparticles were grafted with PS and poly(3-vinylpyridine) (P3VP) by SI-NMP and the resulting PS- and P3VP-grafted magnetite particles were stably dispersed in the appropriate solvents [85–87]. Binder et al. prepared core/shell c-Fe2O3 nanoparticles with a well-defined poly(N-isopropylacrylamides) (PNIPAM)-shell by SI-NMP (Fig. 6) [88]. Robbes et al. presented a new multi-step efficient ‘‘grafting from” method to obtain well-defined magnetic c-Fe2O3 nanoparticles grafted with polystyrene (PS) chains [89]. The PS-grafted magnetic nanoparticles are of interest due to applications such as drug delivery and targeting carrier systems. The NMP technique can be used to functionalize the surfaces of carbon nanotubes (CNTs) which exhibit remarkable elec- tronic and mechanical properties [90–92]. Datsyuk et al. reported in situ NMP of methyl acrylate (MA) on double-walled CNTs (DWCNTs) to obtain the DWCNT-PAA-PMA or DWCNT-PS-PMA composites [93]. The main advantage of this two- step synthetic route is that it does not involve any pre-treatment or functionalization of the CNTs. However, Dehonor et al. reported direct free-radical functionalization of CNTs with BPO/TEMPO followed by SI-NMP of styrene without an acid treatment. The peroxide group was first attached to the CNT surface to create a resonant radical that could trap nitroxide [94]. In situ polymerization of PS-grafted CNTs by NMP did not induce extensive damage on the CNT surface [94] and the acid treatment was very useful in surface functionalization. Zhao et al. used the acid treatment to introduce carboxyl groups to the surface of multi-walled carbon nanotubes (MWNTs) (Fig. 7) to enable further reaction with TEMPO-based alkoxyamine bearing a hydroxyl group to prepare a MWNT-supported initiator [95,96]. The initiator was used to obtain MWNT-PS [95] or MWNT-poly(4-vinylpyridine) (P4VP) [96], respectively via SI-NMP. The MWNT-PS showed relatively good dispersibility in various organic solvents and the MWNT-P4VP exhibited good dispersibility in acidic aqueous solutions as the dispersibility of MWNTs was a reflection of the solubility of the attached polymer [95,96]. The MWNT-PS-P4VP showed different dispersibility characteristics than the other two samples. Water-soluble MWNTs are expected to have applications in supramolecular chemistry and biochemistry.

Fig. 7. Synthesis of the MWNT-supported alkoxyamine initiator [96]. Copyright 2006. Adapted with permission from the Royal Society of Chemistry. 198 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

2.2.3. Biopolymers Common biopolymers include polysaccharides, polypeptides, proteins, polyethylene, polycaprolactone and others and NMP has been applied to polymer-protein/peptide bioconjugates [97]. For example, Chenal designed a protein/peptide PEGylation system based on functional comb-shaped polymethacrylates with poly (ethylene glycol) (PEG) side chains [98]. Möller and co-workers obtained peptide-polymer conjugates with well-deﬁned linear peptide backbones and multiple numbers of PS or poly PNIPAM side chains via NMP [99]. Because the composition, number, and length of the polymer side chains vary, the conjugates aggregate to different structures. For example, peptide-PS conjugates may aggregate to honeycomb structures, whereas peptide-PNIPAM conjugates show a differentiated aggregation behavior. As a natural polysaccharide, chitosan has been grafted by NMP to obtain functionalized copolymers with controlled molecular weights and ‘‘well-deﬁned” structures and good biocompatibility, biodegradability, bioactivity, as well as antibacterial and wound-healing activity have been observed from grafted chitosan [100–102].

2.2.4. Others Besides the aformentioned traditional biomaterials, other biomaterials can be modiﬁed by this method [103–117]. Zhao prepared mixed polymer brushes on the silicon wafer using a combination of ATRP and NMP (Fig. 8) [103–106]. Owing to the unique structure, these mixed homopolymer brushes exhibited reversible changes in the surface properties in different solvents [103,106] and even formed relatively ordered nanoscale domains [105–106]. As shown in Fig. 9 [106,112], exposing

Fig. 8. Synthesis of mixed PMMA/PS brushes from an asymmetric difunctional initiator-terminated SAM (Y-SAM) by combining ATRP and NMP techniques [106]. Copyright 2004. Adapted with permission from the American Chemical Society.

Fig. 9. Solvent-dependent reorganization of the binary polymer brushes [112]. Copyright 2009. Adapted with permission from Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 199 the wafer to the polar solvent glacial acetic acid induced the polar polymer chains of PMMA to move to the outermost layer, while the apolar polymer brushes of PS were buried in the polymer film. The non-selective solvent CHCl3 yielded a statistical mixture of polar and apolar polymer brushes at the surface. In contrast, in the apolar solvent cyclohexane, the polar PMMA brushes aggregated in the film while the apolar PS brushes stretched to the outside. Studer and co-workers demonstrated that PS brushes prepared by SI-NMP on silicon wafers possessed either protein adsorption or protein repellent properties depending on the thickness of the PS brush [113,116,117]. They found that PS brushes with thicknesses larger than 45 nm exhibited a surprising degree of protein repellence, whereas protein adsorption was observed from PS brushes with thicknesses below 20 nm [116]. PNIPAM brushes have been reported to have good protein resistance at room temperature [118]. Cimen and Caykara modified the surface of silicon wafers by grafting biofunctional PNIPAM with a high density of amine groups to immobilize a range of antigens or ligands in biosensing applications and to study cell-surface interactions. The process of SI-NMP of NIPAM is depicted in Fig. 10 [115]. PEG and PEG-based materials have been used to modify biomaterials by NMP because of the ability of PEG to resist protein and cell adhesion in addition to its non-toxicity and non-immunogenicity [98,107]. By using the same method, poly(carboxybetaine methacrylate) (PCBMA) was grafted onto a silicon wafer to obtain polymer brushes that were able to suppress protein adsorption, while the terminal phosphonate group might promote endothelial adhesion [114]. Owing to their surface chemistry, outstanding optical properties and target specificity, quantum dots (QDs) such as CdSe, CdS, and CdTe are often used in immunolabeling, cell tracking, and in vivo imaging [119–121]. However, the processability, shelf-life stability, and relevant applications of these QDs are usually determined by the nature of the ligand periphery. The applicability ultimately depends on the performance of these specific platforms. Sill et al. demonstrated the growth of PS and P(styrene-co-methyl methacrylate (MMA)) copolymers on CdSe nanoparticles by NMP (Fig. 11) [122]. While free radicals can quench the fluorescence of CdSe nanoparticles, NMP allowed fluorescence of the prepared composites to be maintained due to the low concentration of radicals inherent to this CLRP technique. In summery, almost all biomaterials including biometals, biopolymers, bioceramics, and nanomaterials can be grafted with various types of bioactive polymers by NMP to achieve specific biological functions such as hydrophilicity/hydrophobi city, antibacterial performance, bioactivity, and so on (Table 1) [66,67,74–81,83–88,93–96,98,99,101–117,122].

Fig. 11. Ligand exchange and polymerization of styrene from nitroxide-functionalized CdSe quantum dots [122]. Copyright 2004. Adapted with permission from the American Chemical Society. 200 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

Table 1 Typical biomaterial grafted with bioactive polymers through NMP.

Substrate Grafted polymer Ref. Biometals Stainless steel Poly(n-butyl acrylate) [66,67] Bioceramics Silica PS [74–81]

Titanium oxide (TiO2) nanoparticles PS [83,84]

Fe3O4 nanoparticles P3VP [85]

Fe2O3 nanoparticles PNIPAM [88] Carbon nanotubes PAA, P4VP [93–96] Biopolymers Peptide/protein PEGMA [98] Peptide PNIPAM [99] Chitosan PMMA, PSS [101,102] Others Silicon wafers PEG, PNIPAM, PCBMA [103–117] Quantum dots PS [122]

2.3. ‘‘Grafting to” route

In some cases, new biomaterials like carbon nanotubes can be modified by SI-NMP method by adopting the ‘‘grafting to” approach because a covalent carbon–carbon linkage can be formed when the surface reacts with the radicals produced by thermolysis of the nitroxide-end capped polymer chains. The well-defined poly(2-vinylpyridine) (P2VP) was synthesized on MWNTs and the resulting materials were easily dispersed in organic solvents as well as acidic water too immobilize the metal nanoclusters on the surface [91]. P4VP, PAA, and PS could also be grafted onto MWNTs by this technique [123,124]. Similarly, Charleux and co-workers employed this process to graft a variety of polymer chains onto primary- amine functionalized silica nanoparticles under soft conditions and the polymer grafting densities were 0.1–0.2 chain nm2 [125]. This approach has also often been employed to modify the silicon wafers. A convenient route is to link the NMP- derived polymer by the ‘‘grafting to” process to the silicon wafer, followed by end-grafting the corresponding polymer to the silanol groups on the surface through the hydroxyl group of 4-hydroxy-TEMPO. Drockenmuller et al. reported another approach for grafting polymer brushes onto passivated silicon surfaces and well-defined PEG, PMMA, and PS brushes with a thickness of 6 nm and density of 0.2 chains nm2 were prepared [126].

2.4. Factors inﬂuencing the properties of polymerized ﬁlms by NMP

The properties of the polymer brushes such as the grafting density, molecular weight, molecular weight distribution, composition, as well as number and length of polymer chains play important roles in the performance of the biomaterials. The grafting density of the polymer brushes is related to microphase separation. Bao and co-workers studied the effects of the grafting density on microphase separation of PtBA/PS brushes by changing the grafting densities but maintaining similar molecular weights and individual grafting densities for two polymers [80]. Microphase separation became weaker as the grafting density decreased and no microphase separation was observed when the grafting density was sufficiently small. The molecular weight of the polymer brushes not only changes the colloidal stability and dispersibility of the biomaterials, but also influences the solubility of biomaterials in addition to the grafting density of the polymer. Bartholome et al. observed that the colloidal stability and dispersibility of silica particles in toluene was significantly improved when the molecular weight of the grafted PS chains was larger than 20,000 by focusing on alkoxyamine initiators of which the grafting density was proportional to the amount of grafted polymer chains [74]. Homenick and co-workers studied the carbon nanotube solubility by polymer grafting and reported that neither a large polymer grafting density nor polymer alone produced the maximum solubility, whereas maximum solubility was achieved with a polymer with an intermediate molecular weight having a relatively large grafting density [127]. Owing to the difference in the composition, number, and length of the polymer side chains, the conjugates aggregate to different structures. The aggregation behavior of peptide-polymer conjugates was studied by Möller et al. [99]. Linear conjugates could form much larger aggregates and show sharp phase transitions, but comb type conjugates could precipitate into particles with a limited size. When the peptide side chains were short and the compositions of the peptide side chains were different, the peptide-PS conjugates aggregated to the honeycomb structures, whereas peptide-PNIPAM conjugates aggregated to the ring-shape topology. When the composition of the peptide side chains was the same and the peptide side chains were different, peptide-PS conjugates bearing small side polymer chains aggregated to the honeycomb structures with a coral like morphology for systems with longer side chains. Peptide-PNIPAM conjugates showed a different aggregation behavior with the different length of the peptide side chains [99]. The thickness of the polymer brushes affects protein adsorption and repelling [113,116,117,128]. The PS brushes exhibited a surprising degree of protein repellence when the PS brushes were larger than 40 nm, whereas brushes smaller than 20 nm showed a protein adsorption behavior [113]. Halperin also demonstrated that secondary protein adsorption was repressed by increasing the brush thickness while primary protein adsorption was repressed by increasing the grafting thickness [128]. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 201

Although NMP has been widely used to modify biomaterials, few studies have been carried out to explore the effects of the modiﬁcation on biological functions. Most studies have focused on surface properties such as antibacterial characteristics or antifouling, hydrophilicity or hydrophobicity, surface potentials, and surface biocompatibility. The in vitro and in vivo biological reactions between NMP-functionalized biomaterials and cells or tissues should be studied in the near future.

3. Atom transfer radical polymerization

In comparison with other CLRP techniques, ATRP is particularly attractive because this polymerization process can be easily controlled, enabling the achievement of a low polydispersity index and eliminating the need for involved puriﬁcation post-synthesis [129–131]. Surface-initiated ATRP is more accessible than NMP because it is easier to synthesize thiol and silane-derivatized surface-bound initiators than the AIBN-silane derivative or the nitroxide silane derivative in NMP.

3.1. Fundamentals of ATRP

Control of radical polymerization depends on two principles [130]. First of all, initiation should be rapid to provide a constant concentration of the growing polymer chains. Secondly, the majority of the polymer chains are dormant so that they can retain the ability to grow based on the dynamic equilibrium between the dormant species and growing radicals. ATRP follows these principles by involving a transition metal halide and a suitable ligand [132] and the mechanism is described in Fig. 12 [133]. Due to the complex catalyst, the equilibrium between the active and dormant species is reversible. In ATRP, the reaction between the alkyl halide initiators or dormant species (RX or Pn–X) and activator-metal complexes Mtn/L with a low oxidation state, where Mtn represents the transition metal species with the oxidation state n and L is a ligand, reversibly generates the propagating radicals (R/Pn) and deactivator-higher-oxidation-state metal complexes X–Mtn+1–Y/L. These radicals initiate polymerization by forming a double bond with the monomer, propagate, terminate by either coupling or disproportionation, or are reversibly deactivated by the transition metal complex with the higher oxidation state [134,135]. When the concentration of the propagating radicals is sufﬁciently small compared to the dormant species, the proportion of chains terminated by bimolecular recombination can often be neglected (<5%). The small concentrations of propagating radicals suppresses termination and enables the production of highly functional polymers (>95%). Thus, the concentration of active species or propagating radicals remains at a very low level throughout polymerization. As ATRP is a catalytic process, it can be mediated by redox-active transition metal complexes such as Cu, Fe, Mo, Os, and Ru [130,132,136– 155]. However, the rate of ATRP does not depend on the absolute catalyst concentration, but rather the ratio of the activator to deactivator concentration. This is because the rate constants and the ratio (KATRP = kact/kdeact) determine the radical concentration and rates of polymerization and termination as well as polydispersity. The key to the success of ATRP is to employ a proper catalytic system with high activity and selectivity. Recently, initiation systems have been developed to utilize a very small amount of active catalyst and to constantly convert the deactivator to an activator by a redox process. Compared to other radical grafting methods, ATRP minimizes radical–radical coupling at the surface due to site-speciﬁc initiation and ATRP equilibrium, which reduces the radical concentration and termination.

3.2. Surface grafting of biomaterials by ATRP

Because of the controlled nature of the reversible activation–deactivation reaction between the growing polymer chain and a copper-ligand species, ATRP is compatible with various types of monomers. Some monomers with special functional groups are often grafted onto substrates such as PMMA, PS, and others by ATRP to achieve speciﬁc antifouling, antibacterial, and stimuli-responsive properties (Table 2) [156–242].

3.2.1. Functionalized surface coatings 3.2.1.1. Antifouling coatings. Biomaterials with antifouling coatings are resistant to cell adhesion and non-speciﬁc protein adsorption. These are important characteristics to prevent undesirable events such as platelet adhesion, thrombus formation, foreign body reaction, bacterial infection, and adhesion of macrophages [156–160]. Antifouling surfaces are typically hydrophilic and prevent binding with many hydrophobic foulants including non-polar solutes, proteins and bacteria

Table 2 Bioactive surface prepared via surface-initiated ATRP.

Nature of polymeric Grafted monomers Substrate Ref. coating Antifouling coatings PEG-containing Silicon, gold, stainless steel, silica, Ti, magnetite [158–160,162,165,172– methacrylate nanoparticles 177] MPC Silicon, gold [156,157,169,178] SBMA Stainless steel, gold, poly(propylene oxide) [179–182,184] CBMA Gold, glass [180,183,184] HEMA Ti, silicon, protein, peptides [185–189] AAm Silicon, gold, chitosan [190–192] NVP Silicon [193] Antibacterial coatings DMAEMA PP, silicon [196–199] 4VP Stainless steel, microporous polysulfone [200,201]

SPMA Gold, Si/SiO2 [202] TBAEMA PP, LDPE, stainless steel [203–205] Stimuli-responsive NIPAM Silicon, PS, gold nanorods, silica [158,215–219] coatings AA Cellulose membrane, porous nylon membrane, silicon [220–222] 4VP Gold nanoparticles [224] DMAEMA Silica, gold, PS, glass conical nanopore channel [225–230] Others MMA Silicon, magnetite nanoparticles, multiwalled carbon [237–239] nanotubes Styrene Chitosan, silica, multiwalled carbon nanotubes [240–242]

[161]. Biomaterials can be endowed with antifouling properties by ATRP with PEG-containing polymers, zwitterionic group- containing polymers, and other antifouling polymers. 3.2.1.1.1. PEG-containing polymers. PEG-based materials have emerged as common antifouling materials due to the good antifouling effects against a wide variety of proteins, suppression of platelet adhesion, and reduction of cell attachment and growth [162–165]. Dense ‘non-fouling’ polymer brushes have been synthesized by ATRP of various PEG macromono- mers on gold [159,160], silica [158,162,165,172,175],Ti[176,177], stainless steel [177], and magnetic nanoparticles (MNPs) [173,174]. Chilkoti reported that poly(oligo(ethylene glycol) methacrylate) (polyOEGMA) brushes grafted on gold substrates by ATRP prevented non-specific cell adhesion for up to 30 days [159]. Ti substrates coated with PEG brushes approximately 100 nm thickness were shown to have excellent resistance against cell adhesion for up to 3 weeks [176] and PEGylated MNPs resisted non-specific protein adsorption better than the pristine nanoparticles [173]. After PEGylation, the uptake of MNPs by the macrophage cells was reduced to 2 pg/cell while the pristine MNPs were taken up very effectively (Fig. 13) [174]. The morphology and viability of the macrophage cells cultured in a medium containing the PEGylated MNPs were similar to those of cells in the control experiment without the nanoparticles (Fig. 13), indicating that this amount of PEGylated MNP uptake did not induce significant cytotoxicity. However, PEG being a polyether autoxidizes readily in the presence of oxygen and transition metal ions often resulting in the cleavage of the ethylene oxide units and formation of reactive aldehyde moieties [166–168]. 3.2.1.1.2. Zwitterionic group-containing polymers. Zwitterionic surfaces resist non-specific protein adsorption via a hydrated layer formed by solvation of the charged terminal groups by electrostatic interactions in addition to hydrogen bonding [169–171]. Zwitterionic monomers undergoing ATRP include 2-methacryloyloxyethyl phosphorylcholine (MPC) [156,157,169,178], sulfobetaine methacrylate (SBMA) [179–182,184], and carboxybetaine methacrylate [180,183,184], with MPC being more difficult to synthesize and handle. Recently, PCBMA-grafted surfaces have been shown to have improved resistance against non-specific protein adsorption in human serum and plasma compared to polyPEGMA- and polySBMA- grafted surfaces, indicating that zwitterionic polymers prepared by ATRP are a viable alternative to PEG-based materials enabling a variety of applications such as diagnostics and drug delivery [184]. Dopamine and organosilane are often used as a bridge to yield a better combination between the substrate and the polymer, while self-assembled monolayers (SAMs) are usually used to synthesize non-fouling coatings with an appropriate graft density due to the large surface density and ease of preparation. Sin and co-worker compared the effectiveness of polySBMA brushes grown from dopamine and silane-assembly layers on stainless steel (SUS) by ATRP in resisting adhesion of proteins, cells, and bacteria [179]. As shown in Fig. 14, both the dopamine and organosilane produced substrates with active amino groups and allowed the subsequent grafting reactions to continue. As shown in Fig. 15a, fibrinogen from the blood plasma was used as a model protein to assess the ability of a non-bioadhesive surface to resist protein adsorption, with polystyrene used as a reference polymer due to its 100% relative fibrinogen adsorption. Compared to SUS (approximately 85%), fibrinogen adsorption of SUS-D-pSBMA (1%) was much less than that of SUS-Si-pSBMA (8%). The relative cell adhesion density of SUS- D-pSBMA was also smaller than that of SUS-Si-pSBMA in both MG63 and HT1080 as shown in Fig. 15b, which presents a statistical analysis of relative cell adhesion on the substrate surface. As shown in Fig. 15c, E. coli and Staphylococcus epidermidis (S. epidermidis) commonly related to infection on orthopedic implants were utilized to evaluate the antibacterial activity [194]. The SUS-D-pSBMA surface resisted bacterial adhesion with only 0.8% E. coli adhesion and 0.02% S. epidermidis T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 203

Fig. 13. (a) RAW 264.7 cells in control culture (without any nanoparticles) after 1 day, (b) cells after culturing in medium containing pristine magnetic nanoparticles (0.2 mg/mL) for 1 day and (c) for 4 days, and (d) cells after culturing in medium containing P(PEGMA)-immobilized nanoparticles (0.2 mg/mL) for 1 day. The P(PEGMA)-immobilized nanoparticles were obtained after polymerization time of 2 h. Scale bar = 40 lm [174]. Copyright 2006. Adapted with permission from the American Chemical Society.

Fig. 14. Schematic illustration of the preparation process of zwitterionic polySBMA grafting from stainless steel via ATRP using (a) catechol dopamine and (b) organosilane as respective self-assembly anchoring agent [179]. Copyright 2014. Adapted with permission from the American Chemical Society. adhesion, whereas signiﬁcant amounts of bacteria adhered to the SUS-Si-pSBMA surface (1.2% E. coli adhesion and 1.5% S. epidermidis adhesion, respectively). These results showed that the polySBMA grafted from dopamine had better adhesion resistance than polySBMA from silane.

3.2.1.1.3. Other antifouling polymers. In addition to PEG and zwitterionic polymers, some polymers such as poly (2-hydroxyethyl methacrylate) (PHEMA) [185–189], poly(acrylamide) (PAAm) [190–192] and poly(N-vinyl-2-pyrrolidone) (PNVP) [193], also possess excellent antifouling properties. Dense hydrophilic PHEMA brushes exhibited excellent protein repellency and well-deﬁned antifouling PHEMA brushes grafted by ATRP also prevented cell adhesion. Consequently, surfaces with a well-deﬁned density gradient of PHEMA brushes could be prepared to tailor cell adhesion [189]. Grafting a densely packed and covalently attached PAAm brush layer from a silicon wafer by ATRP reduced the attractive force between the surface and microorganisms and this approach has great potential in mitigating infection on implants [191]. Ultra-low fouling surfaces were prepared by grafting PAAm brushes on gold surfaces by surface-initiated ATRP [190]. The 204 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

Fig. 15. Statistical analysis of (a) relative fibrinogen adsorption and water contact angle, (b) adherent human MG63 osteoblast and HT1080 fibroblast cells density, and (c) percentage of occupied area of E. coli and S. epidermidis attachment on various surface-modified stainless steel coupons [179]. Copyright 2014. Adapted with permission from the American Chemical Society.

PAAm-grafted surfaces resisted protein adsorption and adhesion of bovine aortic endothelial cells (BAECs) and inhibited attachment of S. epidermidis and P. aeruginosa.

3.2.1.2. Antibacterial coatings. Infection is a great concern for implants and medical devices resulting in orbidity, mortality, and medical costs [194]. To obtain antimicrobial surfaces to prevent infection, active antimicrobial agents are introduced to biomaterials by covalent interactions. In general, the antibacterial brush coatings can be subdivided into three categories: (1) polymer brushes composed of a bactericidal polymer, (2) polymer brushes functionalized with a bactericidal or bacterio- T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 205 static compound covalently linked to the brush, and (3) nonfouling polymer brushes that aim at repelling bacterial adhesion and mitigating biofilm formation [195]. 3.2.1.2.1. Bactericidal polymer brushes. Bactericidal polymers generally contain cationic groups such as alkyl pyridinium or quaternary ammonium moieties. Cationic bactericidal polymers including vinyl monomers with tertiary amino groups such as 2-dimethylaminoethyl methacrylate (DMAEMA) and 4-vinyl pyridine (4VP) can endow biomaterials with self- antibacterial abilities by two steps. The first step is polymerization or copolymerization by ATRP followed by quaternization [196,197]. In this reaction, quaternization of the amino groups of poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) or P4VP brushes by an alkyl halide produces the biocidal functionality on the surface of the polymer-modified inorganic materials [196–200]. However, different alkyl halides are used in the reactions to prepare PDMAEMA or P4VP brushes, namely ethyl bromide and hexyl bromide, respectively [196,198,200]. These modified surfaces exhibit substantial antimicrobial capacity [196–201]. In addition to cationic antibacterial materials, anionic polyelectrolyte brushes of poly(3-sulfopropylme thacrylate) are synthesized by ATRP of 3-sulfopropylmethacrylate (SPMA) in a controlled manner and then introducing antibacterial silver ions to the polyelectrolyte film [202]. The silver-loaded sulfonate brushes inhibit the growth of both Gram-negative and Gram-positive bacteria. The brushes exhibit slow leaching of silver ions but retention of the silver ions at the surface. The silver-loaded sulfonate brushes possess the desirable properties of an antibacterial surface [202]. Additionally, the neutral polymer poly(2-(tert-butylamino)ethyl methacrylate) (PTBAEMA), a typical representative water-insoluble biocide, has been used to prepare antibacterial surfaces by ATRP [203–205]. For instance, the modified LDPE exhibits effective antimicrobial activity [203]. Anchoring of the PTBAEMA chains onto PP produces long-lasting antibacterial activity [205] and similarly, bacterial adhesion on the modified stainless steel diminishes significantly [204]. The major role of PTBAEMA is believed to be the displacement of Ca2+ and/or Mg2+ ions from the outer bacterial membrane thereby disrupt- ing and compromising the membrane functions. 3.2.1.2.2. Polymer brushes functionalized with antibacterial compounds. In addition to directly grafting antibacterial polymers, a polymer brush without antibacterial properties can first be formed on the substrate by ATRP, followed by covalent linkage of an antimicrobial compound to the polymer brush. Antimicrobial peptides (AMPs) are attractive antibacterial compounds due to the broad spectrum activity against both Gram-negative and Gram-positive bacteria and relatively lack of toxicity towards host cells [206–208]. Recent studies about this type of antibacterial coating were carried out on a Ti surface [208–210]. Copolymer poly-(N,N-dimethylacrylamide-co-N-(3-aminopropyl)-methacrylamide hydrochloride) (poly(DMA- co-APMA)) brushes were synthesized by ATRP and different types of AMPs were conjugated to the copolymer brushes by the maleimide groups [208–210]. The peptides immobilized on the copolymer brush are shown in Fig. 16 [209]. The peptide density on the surface was larger when the brush layer was used for peptide conjugation than when the peptides were directly grafted onto the surface [208]. The AMP-immobilized polymer brushes also had excellent broad spectrum antimicrobial activity and biofilm resistance in vitro, depending on the types of AMPs [209,210]. 3.2.1.2.3. Antifouling polymer brushes with antibacterial properties. Antifouling polymer brushes are resistant to bacteria in addition to preventing cell adhesion and non-specific protein adsorption. For example, as shown in Fig. 15c, the stainless steel surface grafted with polySBMA brushes by ATRP shows excellent resistance to bacterial adhesion.

3.2.1.3. Stimuli-responsive coatings. Stimuli-responsive polymers play an important role in biomedical applications such as drug delivery, biomolecular diagnostics/biosensors, and others [51,211–214]. Stimuli can be divided into physical stimuli such as temperature, pressure, electrical stimuli or magnetic ﬁelds as well as chemical stimuli such as pH, ionic strength and chemical agents [211]. Temperature-sensitive polymers (also called thermo-responsive polymers) and pH-sensitive polymers are the most commonly studied stimuli-responsive materials. Owing to the lower critical solution temperature (LCST) of approximately 32 °C in an aqueous medium, PNIPAM is the most extensively studied thermo-responsive polymer. Well-deﬁned PNIPAM can be prepared by ATRP to control the cell behavior [158,215,216] and drug delivery [217,218]. Fig. 17 shows the mechanism of temperature-responsive PNIPAM

Fig. 16. Representation of peptide immobilized copolymer brush on surface [209]. Copyright 2011. Adapted with permission from Elsevier Science Ltd. 206 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

[133]. Below the LCST, hydrogen bonds form. The PNIPAM chains extend and a stable hydration shell forms around the hydrophobic groups. Above the LCST, hydrogen bonding weakens and the intrinsic affinity of PNIPAM chains dominates. The pH-responsive polymers consist of ionizable pendants that can accept and donate protons in response to changes in pH, while polymers containing ionizable groups in their backbone can form polyelectrolytes in an aqueous system. There are two types of pH-responsive polyelectrolytes: weak polyacids and weak polybases. Weak polyacids such as PAA or poly (methacrylic acid) (PMAA) accept protons at low pH and release them at neutral and high pH, whereas polybases such as P4VP are protonated at high pH and become positively ionized at neutral and low pH [18,211]. These pH-responsive polymers can be anchored onto the surface by ATRP to produce polymer brushes [220–224] and applications of pH-responsive polymers include drug delivery and intracellular delivery in gene therapy [211]. PDMAEMA is both temperature- and pH-sensitive because it has amine pendant groups that can gain protons and can be positively ionized at neutral and low-pH conditions. It has a LCST of 40–50 °C and a pKa of 7.0–7.5 [226–229]. The LCST of PDMAEMA is strongly dependent on pH with no LCST at low pH [231,232]. The PDMAEMA-modified nanopore channels prepared by ATRP have high gating efficiency and reversibility, which may stimulate future applications in biosensors and actuators [229,230]. Furthermore, PDMAEMA can be used to prepare novel controlled drug release systems in the near future. In addition to the four properties described above, some polymers such as MMA and styrene can be grafted onto biomaterials by ATRP to facilitate grafting of functionalized polymeric groups onto these materials [237–242].

3.2.2. Factors influencing the properties of polymerized films by ATRP The properties of surfaces such as protein adsorption and adhesion, cell adhesion behavior, and so on can be affected by the thickness, grafting density, molecular weight, and chain length of the polymer brushes formed by ATRP. The thickness of the polymer brushes affects serum protein adsorption and fibroblast adhesion. Serum protein adsorption and fibroblast adhesion were effectively reduced, when the thickness of the poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) or PNVP brush layer increased [178,193]. The surface hydrophilicity increased when thick PNIPAM brushes were grafted onto the surface because of more extended chain conformation with relatively high chain mobility accompanying polymer chain hydration [215]. When the thickness of the polymer brush is taken in account together with the grafting density, peptide adsorption and cell attachment can be regulated [160]. By adjusting the grafting density of the polymer brush, cell adhesion and cell morphology can be controlled [189]. Cells adhered and spread and fibronectin adsorbed on the low graft density end, whereas there were fibronectin repulsion, and little cell adhesion and spreading at the high graft density end [189]. The low-density PNIPAM brush also showed the highest cell adhesion, featuring adherent cells with an elongated morphology [243]. Halperin and Kröger’s research revealed that protein adsorption could be effected by grafting density and polymerization degree of the PNIPAM chain [244]. The molecular weight of the polymer brush influences protein adsorption [182]. The copolymers containing polySBMA with a larger molecular weight had high protein adsorption after direct adsorption onto a hydrophobic surface [182]. When the grafting density was the same, the surface grafted with a relatively large molecular weight PDMAEMA showed almost 100% killing efficiency [198]. Both the graft density and chain length affected protein adsorption [156]. The surfaces with large graft densities and PMPC chain lengths showed a dramatic reduction in the fibrinogen adsorption and fibrinogen adsorption depended more on the graft density than chain length [156].

4. Reversible addition-fragmentation chain transfer polymerization

RAFT polymerization is a versatile technique and addition-fragmentation transfer agents were directly utilized to control radical polymerization in the mid 1980 s [245,246]. RAFT polymerization is different from the other CLRP methods in that it is compatible with a wide range of monomers and reaction conditions. This is because the conditions for RAFT polymeriza- T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 207 tion are similar to those in conventional radical polymerization except the added RAFT agent. Most monomers that are poly- merizable by conventional radical polymerization can be polymerized by RAFT contrary to other CLRP methods [247–249]. RAFT polymerization can be utilized to form narrow polydispersity polymers or copolymers with controllable molecular weights and achieve high conversion and commercially acceptable polymerization rates.

4.1. Fundamentals of RAFT polymerization

Conventional RAFT polymerization contains three primary components: a monomer, a radical initiator, and a chain transfer agent. The key to successful RAFT is the appropriate selection of the RAFT agent or RAFT chain transfer agent (CTA). Trans- fer agents including various dithioesters, dithiocarbamates, trithiocarbonates, and xanthates have been used to control the molecular weight, molecular weight distribution, and even molecular architecture and some thiocarbonylthio compounds are the most effective transfer agents [41,247,248,250,251]. The mechanism of exchange between dormant and active species involves a series of linked equilibria and so the sequence of addition-fragmentation equilibria is important to RAFT polymerization, as shown in Fig. 18 [252]. The polydispersity and molecular weight control depend on the nature of the groups Z and R in the thiocarbonylthio compounds (S@C(Z) SR) in which the reactive C@S double bond and weak SAR single bond are key structures. When selecting Z and R, it is critical to determine both the addition and fragmentation rates of the RAFT agent as they can alter the effectiveness of the RAFT agent [253]. Z, a group that modifies the reactivity of the thiocarbonylthio compound and derived adduct radical, should activate the C@S double bond towards radical addition in order to ensure a high transfer constant, and this is a major factor affecting the lifetime of the intermediate radical resulting from the addition of a radical species across the C@S bond. The R group allows for fine tuning of the overall reactivity, thus enabling these species to effectively mediate polymerization in a controlled manner. It has a profound effect on the polymerization kinetics and overall degree of control. The R group plays two roles. First of all, it should be a good free radical leaving group and secondly, the radial (R) generated from homolytic dissociation must efficiently reinitiate polymerization to induce chain transfer. The structures of the Z and R groups are closely related and not all combinations of Z and R groups produce the effective/efficient RAFT agents. While initiation and radical–radical termination can occur in conventional radical polymerization, RAFT is simply a conventional free radical polymerization technique that utilizes the suitable thiocarbonylthio species. In the early stages of polymerization, fragmentation of the intermediate radical provides a polymeric thiocarbonylthio compound [PnS(Z)C@S (3)] and new radical (R ) by adding a propagating radical (Pn ) to the thiocarbonylthio compound [RSC(Z)@S(1)]. The radical (R ) reacts with a monomer to form a new propagating radical (Pm ). Chain extension of the polymeric thiocarbonylthio

Fig. 18. The mechanism of reversible addition-fragmentation chain transfer [252]. Copyright 2009. Reproduced from Moad et al. (2009), with permission from CSIRO Publishing. 208 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

compound [PnS(Z)C@S(3)] involves essentially the same process, while rapid equilibrium between the active propagating radicals (Pn and Pm ) and dormant polymeric thiocarbonylthio compounds (3) results in an equal probability for all the chains to evolve into polymers with narrow dispersity. When polymerization is complete, most of these chains retain the thiocarbonylthio end-group and are stable. At least four factors determine the effectiveness of the thiocarbonylthio compound (1) on the basis of the addition- fragmentation mechanism: (a) the rate constant of the reaction of the thiocarbonylthio compound (1) with the propagating

(or initiating) radicals (kadd), (b) the absolute rate constant of the reaction with the intermediate radical (2) fragments (kb), (c) partitioning of the adduct (2) between the starting materials and products (determined by the relative magnitude of kadd and kb), and (d) the rate and efﬁciency at which the expelled radicals (R ) reinitiate polymerization. RAFT polymerization features a different mechanism to achieve control than ATRP and NMP. In ATRP and NMP, by reversible deactivation of the propagating radicals, radicals can also be derived from the dormant species. In contrast, in RAFT polymerization, an external source of free radicals is required to initiate and maintain polymerization because free radicals are neither formed nor destroyed in the process and the deactivation-activation equilibrium are chain-transfer reactions. The rate of polymerization is determined by the combined effects of the deactivation-activation equilibrium and ‘‘persistent radical effect” [248].

4.2. Surface polymerization of biomaterials by RAFT

Surface RAFT polymerization can be divided into three categories according to the type of species anchored to the substrate: (1) initiator, (2) CTA via the Z-group, and (3) CTA via the R-group. The initiator approach yields low grafting densities due to radical recombination. Because the radical chains have to diffuse through the polymer layer to react with the RAFT agent immobilized on the surface, the polymer chain does not grow from the surface. The Z-group approach is not a surface-initiated polymerization/grafting-from method and has the same limitations as the typical grafting-to method known as the autophobic effect for polymer brushes [254,255]. The R-group approach is the most effective way to obtain thick polymer brushes with a narrow molecular weight distribution. Polymerization is initiated in a solution with or without a sacriﬁcial CTA. Fig. 19 compares the R-group and Z-group approaches with regard to CTA-anchored surface-initiated RAFT polymerization [255].

4.2.1. Monomers used in RAFT polymerization Monomers with functional groups such as hydroxyl groups, carboxylic acids, carboxylic acid salts, amides, and tertiary amines can be used in RAFT polymerization. The typical monomers used to modify biomaterial surfaces via RAFT polymerization include styrene derivatives, acrylates and acrylamides, methacrylates, and methacrylamides and vinyl esters, as shown in Table 3 [256–285]. RAFT polymerization can be used to immobilize functional polymers such as PS, PAA, and PNIPAM in the maleimidated surfaces [257]. Fig. 20 depicts the process of immobilization of thiol-terminated polymers on the maleimidated surfaces. The trithiocarbonate-terminated polymers are ﬁrst synthesized by RAFT polymerization, followed by conversion of the trithiocarbonate group to a thiol group by NaBH4 reduction [257]. Fig. 21 schematically illustrates the process of grafting MMA onto the surface of biomedical stainless steel by RAFT polymerization [271]. This method can be combined with other techniques to functionalize biomaterials. For example, RAFT and the ‘‘graft from” strategy were employed to integrate the copolymers of positive charged quaternary amines and PEG units to modify the surface of mesoporous silica nanoparticles (MSNs). The resulting PEG coating with a large positive zeta potential showed nearly

Fig. 19. The comparison of R-group and Z-group approaches for CTA anchored surface-initiated RAFT polymerizations [255]. Copyright 2011. Adapted with permission from Elsevier Science Ltd. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 209

Table 3 Biomaterial grafted with bioactive polymers through RAFT.

Grafted monomer Substrate Ref. Styrene derivatives Styrene Gold nanorod and nanoparticle, siliceous, silicon wafer, silica particles, cellulose [256–263]

4VP SiO2 nanoparticles [264] Acrylates AA Gold nanorod, siliceous [256,257] Methyl acrylate Silica particles, silicon, gold nanoparticle [259,262,263] PEGA Protein [265,266] HEA Protein [267] Acrylamides NIPAM Siliceous, protein, silica particles, magnetic nanoparticle, chitosan [257,259,260,267–270] DMA Silicon wafer, silica particles [258,259] Methacrylates MMA Stainless steel, Au, silicon wafer, Silica Particles [258–260,262,271,272] DMAEMA Gold nanorod, cellulose, Silicon [256,262,273–276] AHMA Silica Nanoparticles [277] HEMA Silicon wafers [278] PEGMA Gold, silicon wafer, magnetic nanoparticle [269,279,280] PEGMEMA Au [272]

Methacrylamides AEMA Fe3O4 NP [276,281–283] APMA Antimicrobial peptides [281,284] HPMA Au nanoparticle, gold nanoparticle [263,284] DMAPMA Au nanoparticle, Antimicrobial peptides [284,285]

Fig. 20. Preparation of maleimidated surface and immobilization of thiol-terminated polymer via the Michael addition reaction [257]. Copyright 2012. Adapted with permission from the American Chemical Society.

2-fold enhanced permeability and retention (EPR) effect in addition to a longer blood half-life compared to coating with PEG only. The polymerized MSNs showed higher efﬁcacy in doxorubicin (DOX) drug delivery and suppression of side effects compared to the free drug, as conﬁrmed by the in vivo assessment indicating inhibition of tumor growth in tumor-bearing nude mice after intravenous injection of DOX-loaded MSN-PEG+ (shown in Fig. 22) [269].

4.2.2. Factors influencing the properties of polymerized films by RAFT The biocompatibility and antibacterial activity are important to biomaterials, particularly implants. Antimicrobial PEG functionalized polymers synthesized from methacrylate derivatives by RAFT polymerization had shorter hydrophobic chain lengths (i.e., methyl and ethyl) and better antimicrobial properties [286]. DeGrado and Kuroda synthesized antimicrobial poly(methacrylate) derivatives that could be tailored by tuning the molecular size and number of hydrophobic side chains [287]. When the hydrophobic side chains were shorter, the antibacterial activity was higher [274]. The effect of the pendant amine structure on antimicrobial activity in amphiphilic polymethacrylates was investigated [288,289]. The primary amines increased the antimicrobial activity. Polymers containing quaternary ammonium groups increased the antimicrobial potency by adding extra hydrophobic functional groups. However, the homopolymer of the primary amine-containing methacrylamide monomer was found to deliver significantly greater antimicrobial activity than poly(methacrylate) due to improved hydration of the polymer backbone [285]. These results have increased the interest in surface grafting of poly(methacrylamide) via RAFT polymerization to improve the antibacterial activity of biomaterials. Ahmed and co-worker studied the effects of the polymer architecture, composition, and molecular weight on the properties of glycopolymer-based non-viral gene delivery systems [281]. When the architectures (block versus random) were different, the statistical copolymers showed lower toxicity and higher gene expression than the corresponding diblock copolymers in the presence and absence of serum [281]. When the arbohydrate residues in the copolymers increased, the transfection efficiency of the polymers decreased because the critical composition of the carbohydrate segment in the copolymers enhanced gene delivery and had low toxicity [281]. The large molecular weight statistical copolymers showed greater cell viability and gene expression in the presence and absence of serum [281]. Boyer found that a lower critical solu- 210 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

Fig. 21. General procedure for the preparation of CTA-modiﬁed stainless steel surfaces and subsequent formation of PMMA brushes by reversible addition- fragmentation chain transfer polymerization [271]. Copyright 2013. Adapted with permission from the American Chemical Society.

Fig. 22. In vivo inhibition of tumor growth in tumor-bearing nude mice after intravenous injection of DOX-loaded MSN-PEG+. (A) Time dependent tumor growth curves at 3 d, 6 d, 9 d and 12 d after the injections of saline, empty MSN-PEG+, free DOX and DOX-loaded MSN-PEG+. The dosage of the DOX drug was 100 mg per mouse for each administration every six days. ⁄⁄ and ⁄⁄⁄ represent significant differences in tumor growth inhibition found by comparing the four groups at P 6 0.005 and P 6 0.0005, respectively. (B) The photographs of nude mice before and at the end of treatment showing the different tumor growth-inhibition effects. (C) The TUNEL staining assay showing enhanced apoptosis and cell death by DOX-loaded MSN-PEG+ compared to free DOX. The upper blue fluorescence images are of the cell nucleus after DAPT staining. The lower green fluorescence images (200) represent of the TUNEL-positive cells [269]. Copyright 2014. Adapted with permission from the Royal Society of Chemistry. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 211 tion temperature of the conjugates increased with decreasing molecular weight of the PNIPAM block conjugated to BSA [267].

5. Other surface radical polymerization methods

5.1. Plasma-induced radical polymerization

Plasma, a quasi-neutral gas considered as the fourth state of matter, consists of a collection of neutrons, electrons, ions, and other atomic and molecular species [290]. Plasma surface modification is a rapid, dry, economical, effective, and environmentally friendly materials processing technique which is becoming increasingly popular in the biomedical community. This method can enhance the surface properties while preserving the bulk properties [291]. In addition to creating active surface species, it is used to remove contaminants from the polymer surface, an additional benefit that enables the reproducible preparation of a homogenously treated polymer surface [292]. Plasma-induced graft polymerization is a two-step process in which the functional groups and reactive sites are incorporated onto the surface. This process is different from activation in that it adds the materials to the surface instead of func- tionally modifying the surface. It results in a high surface density of the polymer chains which are initiated and polymerized directly from the substrate to enhance the stability with under chemical and thermal stress conditions as well as minimizing the growth of polydispersed chains [293]. Several studies have confirmed that plasma-induced graft polymerization is a desirable method to functionalize interfaces for immobilization of biomolecules [294,295]. In low-pressure plasma methods, the non-thermodynamic-equilibrium processes in weakly ionized gases not only enable the design of a novel class of materials generally in the form of surfaces, but also allow for the modification of the surface properties of any solid substrates compatible with medium–low vacuum conditions [296]. Plasma-induced graft polymerization has hitherto involved low-pressure plasma initiation and surface grafting onto polymeric materials but there have been few studies on inorganic oxides [297–299]. It has been reported that the plasma treatment time and radio frequency (RF) power of the plasma generator can control and optimize the surface radical density [298–300]. However, the radical density on the surface of inorganic oxide substrates modified by the low pressure plasma approach may be limited by the native oxide surface chemistry [301]. These findings indicate that this approach is not sufficient to achieve high- density surface activation and graft polymerization/modification of inorganic substrates with a large surface area. Recently, atmospheric pressure plasma-induced graft polymerization (APP) has been adopted in surface functionalization [294,302–

Fig. 23. Illustration of multistep process plasma-induced graft polymerization [304]. Copyright 2007. Adapted with permission from the American Chemical Society. 212 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

305] and the typical APP process is described in Fig. 23 [304]. A high throughput platform that allows for the synthesis, screening, and selection of the desirable monomers in a relatively short period of time has been combined with atmospheric pressure plasma to synthesize, test, and select the best protein-resistant membranes [302,305]. Different polymers can be grafted on various substrates as shown in Table 4 [292–325]. For instance, 1-vinyl-2- pyrrolidone monomer was polymerized on the surface of silicon by plasma-induced graft polymerization [304]. The surface morphology of the grafted polymer layer depended on the density of the surface-active sites generated by the plasma treatment as well as polymerization conditions suggesting commercial potential of large-scale nanostructured surface treatment. Ti and its alloys have been widely used in biomedical devices but the bioinert nature and susceptibility to bacterial infection restrict wider application to orthopedic implants in vivo. Plasma polymerization using allylamine, acrylic acid (AA) or other monomers as precursors has been applied to modify these metals [307–310]. The modified titanium surface can be further functionalized by attaching the desired molecules such as RGD, PEG, collagen I, or antimicrobial peptides to enhance the osteoinductivity, osteoconductivity, and antibacterial activity. To improve the thromboresistance of the titanium alloy, Ye carried out plasma-induced graft polymerization of MPC and after modification, platelet deposition and bulk phase platelet activation diminished significantly relative to the unmodified titanium alloy [312]. Plasma treatment is also effective for biopolymers. For example, polycarbonate (PC) membranes are good candidates in drug delivery applications due to their unique structure, excellent biocompatibility, and wide commercial availability [313]. Baumann utilized plasma-induced graft polymerization to tune the hydrophilicity and permeability resistance of PC membranes in drug delivery systems [292]. Poly(ethylene terephthalate) (PET) was used to treat the pathology of large-diameter arteries [314,315]. To overcome the chemical and biological inertness of the PET surface, bioactive biomolecules such as AA and gelatin were grafted onto the PET films by plasma-induced polymerization for protein immobilization and smooth muscle cell seeding. The results showed that the collagen immobilized surface provided an excellent substrate for the growth of human smooth muscle cells [294,314]. Some common biocompatible polymers such as PTFE, polyurethanes (PU), and poly(l-lactic acid) (PLLA) can be modified by this method to enhance the biological functions [316–322]. Wang and Chen grafted AA onto a PTFE film using peroxides to initiate polymerization during which PTFE reacted with AA. The remote argon plasma was used to etch the surface to create peroxides after exposure to oxygen [317]. The water contact angles decreased from 108° to 41°, indicating enhanced hydrophilicity after treatment as a result of the permanent AA grafted layer on the surface [317]. In contrast, plasma pre-treatment followed by UV-induced grafting of glycidyl methacrylate (GMA) to PTFE enhanced the hydrophobicity as manifested by the larger contact angle compared to the pristine surface [316]. In addition to varying the hydrophilicity/h ydrophobicity, plasma induced polymerization can be employed to modulate the cellular behavior on biopolymers. Hsu and Chen demonstrated that the lactide-grafted PU surfaces after the plasma-induced graft reactions favored adhesion of 3T3 fibroblasts and human umbilical vein endothelial cells. Platlet activation also decreased demonstrating potential applications of PU vascular grafts [318]. In addition to regulation of the cell adhesion behavior, the cell morphology can be modulated by this technique. Ding et al. immobilized chitosan on PLLA films by plasma graft polymerization [319] and despite no obvious difference in the mouse fibroblasts densities among the three types of surfaces, the cell morphology was quite different. The fibroblasts hardly spread and tended to become round on the modified surface but freely extended on the untreated surface [319]. A similar phenomenon was observed from human hepatocytes, indicating that plasma graft polymerization could be used to control the cell morphology [319]. The plasma-induced polymerized surface can be further functionalized by other polymerization techniques. For example, with regard to stainless steel, pre-treatment with the silane coupling agent was required to provide a suitable grafting environment and the substrate was subsequently activated by an argon plasma prior to undergoing UV-induced graft polymerization with PEGMA (Fig. 24) [306]. The graft concentration was demonstrated to rely on the macromonomer concentration and UV graft polymerization time. The PEGMA graft-polymerized stainless-steel with a large graft concentration was effective in preventing protein adsorption [306]. Plasma-induced graft polymerization can be combined with ATRP to

Table 4 Biomaterial grafted with bioactive polymers through plasma-induced graft polymerization.

Substrate Monomer Ref. Silicon VP [304] Stainless steel PEGMA [306] Titanium AA, allylamine, styrene [307–311] Titanium alloy MPC [312] PC AEMA [292] PET AA [294,314,315] PTFE GMA, AA [316,317]

PU L-lactide [318] PLLA chitosan [319] PS NVP, peptide [323,324] PES methacrylamide derivatives [305] PP AA [325] T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 213

Fig. 24. Schematic illustration of the processes of surface modiﬁcation of stainless steel by silane treatment, Ar plasma treatment and UV-induced surface graft polymerization [306]. Copyright 2001. Adapted with permission from Elsevier Science Ltd. modify biomaterials. The quartz crystal microbalance surfaces were ﬁrst grafted with poly(allyl alcohol) by plasma-induced graft polymerization to create a surface-grafted polymerization initiator and ATRP was then performed to graft poly(tert- butyl acrylate) that was eventually converted into poly(acrylic acid) by hydrolysis [326]. The tethered poly(acrylic acid) grafted quartz crystal microbalance synthesized by this method increased the frequency response to the pH, immobilization amount of the antibody, and immunosensor response [326].

5.2. Radiation-induced radical polymerization

Radiation-induced radical polymerization is well known for its advantages and potential in modifying the physical and chemical properties of pre-existing polymeric materials without altering their inherent properties. Catalysts and additives are not required during this process and the products maintain the purity and molecular weights of the products. The degree of grafting can be controlled. Another merit of the radiation techniques is that the processed materials are not only nontoxic, but also sterilized. Radiation can be used to combine two highly incompatible polymers in a unique way to fabricate graft copolymers with new properties. Common radiation energy sources include gamma ray, UV, and electrons [327]. High-energy irradiation of macromolecules can form polymeric ions and free radicals on the polymer as the result of homolytic ﬁssion [15]. Radiation-induced graft polymerization can be divided into ionic grafting and free-radical grafting. Ionic grafting may be of two different types: cationic or anionic and the potential advantage of ionic grafting is the large reaction rate. MeV proton beams have been successfully applied as ionizing radiation to induce graft polymerization on PP or PE substrates [328–330]. Free-radical grafting is a type of radiation-induced graft polymerization. The basic process of radiation-induced free radical graft polymerization is described in Fig. 25 [331]. When the polymeric substrate ‘A’ is exposed to ionizing radiation as macro-initiators, the active sites formed randomly along the polymer chain initiate free radical polymerization of monomer ‘B’. Unlike chemical initiation, there is no contamination from the initiators. Generally, in radiation initiation, absorption of energy by the backbone polymer initiates a free radical process, while the initiator decomposes into fragments which then attack the base polymer, leading to the generation of free radicals as in chemical initiation.

Fig. 25. The use of ionizing radiation to graft monomer ‘B’ to polymer ‘A’ to form a graft copolymer [331]. Copyright 2003. Adapted with permission from Elsevier Science Ltd. 214 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

Radiation-induced graft polymerization is typically carried out by three routes: (1) simultaneous irradiation, (2) pre- irradiation method, and (3) peroxide-irradiation [332,333]. The simultaneous irradiation method is the simplest one for the preparation of graft copolymers. In this method, the polymer substrate is immersed in a monomer which may be vapor, liquid, or in a bulk solution. When the substrate and monomer are exposed to radiation, free radicals are formed to produce the grafted polymer. The pre-irradiation method consists of two steps. Firstly the polymer substrate is irradiated in vacuum or under an inert atmosphere to generate free radicals and secondly, the irradiated polymer substrate reacts with the monomer after air has been removed. Similarly to the pre-irradiation method, the peroxide-irradiation method only exposes the polymer substrate to the ionizing radiation in the presence of air or oxygen, leading to the formation of peroxides or hydroperoxides on the polymer substrate. When heated in the presence of monomer, the peroxy products decompose to radicals, depending on the nature of the polymeric backbone and irradiation conditions, and these radicals initiate grafting. Each method has its own advantages and disadvantages. The pre-irradiation and peroxidation methods are convenient in that the polymeric substrate can be irradiated and stored for a long period of time before performing the grafting step. It is useful when access to a radiation source is limited. Furthermore, little homopolymer formation occurs and grafting can be performed at any time away from the radiation sources, making the pre-irradiation method an attractive option [334–336]. The graft yields of the simultaneous method are generally higher than those of the pre-irradiation methods due to the smaller radical loss through the decomposition reactions in the latter method. However, the simultaneous method is limited by the high degree of homopolymer formation. The mechanisms of the three processes are presented in Fig. 26 [337]. Similar to plasma polymerization, radiation-induced graft polymerization is a promising technique for the surface mod- iﬁcation of biomaterials because it can enhance the biocompatibility or provide the desired surface chemistry by immobi- lizing certain biomolecules onto the surface of biomaterials that come in contact with blood [338,339]. Casimiro and colleagues grafted 2-hydroxyethyl methacrylate (HEMA) to chitosan using the three methods of chemical initiation, photo-induction and radiation-induced polymerization and radiation-induced polymerization produced a higher graft yield than the other two methods [340]. The monomers commonly used in radiation initiation are MMA, AA, acrylamide (AAm),

Fig. 26. The mechanisms of three different radiation processes [337]. Copyright 2000. Adapted with permission from Elsevier Science Ltd. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 215

NIPAM, HEMA, vinyl alcohol, vinyl pyrrolidone, glycidyl methacrylate, and styrene [333,337,341–348]. Jin et al. grafted HEMA onto dopamine-coated stainless steel by c irradiation and the HEMA grafted stainless steel surface exhibited enhanced hydrophilicity, excellent anti-platelet adhesion, and high hemocompatibility as shown in Fig. 27 [341]. Another important biomedical application of radiation-induced grafting is modification of fabrics such as cotton fabrics and non-woven polypropylene fabrics to obtain specific biological functions [349–352]. Cotton fabrics possess desirable properties such as good folding endurance, breathability, and good bio-degradability, but their major shortcoming is that they are prone to bacterial and fungal growth under moist conditions. Therefore, development of antibacterial fabrics for hospitals is important. Goel prepared antibacterial cotton fabrics by radiation-induced grafting of [2-(methacryloyloxy)et hyl]trimethylammonium chloride onto cotton. The modified cotton exhibited good antibacterial activity against both gram-positive bacteria such as S. aureus and Bacillus cereus and gram-negative bacteria such as E. coli and Pseudomonas fluorescens [349,350]. Although polypropylene non-woven fabrics (PPNWF) have some excellent properties such as non- toxicity, chemical stability and low cost, the poor hydrophilicity and biocompatibility of unmodified PPNWF can often induce thrombus formation due to blood protein adsorption and platelet adhesion [351,353,354]. These shortcomings could be overcome by introducing bioactive groups onto the surface by radiation-induced grafting [351,352]. For example, N-vinyl-2-pyrrolidone could be grafted onto PPNWF using a simultaneous irradiation-induced graft polymerization technique to enhance the surface hemocompatibility of PPNWF [351]. Because some diseases induce changes in the body temperature and/or pH [355–358], Kuamari et al. used a temperature- and pH-responsive monomer (NIPAM, AA) to modify PPNWF, and the morphology of the modified surface was significantly affected by the grafting process [352]. RAFT polymerization could be applied to radiation-induced graft polymerization of styrene from cellulose to prepare highly hydrophobic surfaces [359]. Radiation-induced graft polymerization in combination with NMP is a useful tool in the production of proton exchange membranes for fuel cell applications [360]. The membrane prepared by both radiation-induced graft polymerization and ATRP had better chemical stability than the membrane prepared by conventional radiation-induced grafting [361].

5.3. Photo-induced radical polymerization

Photografting polymerization was first reported in the 1950s. The monomers were photo-grafted by UV radiation onto the polymer substrate blended with a photoinitiator [362]. By adopting high energy irradiation initiated surface polymerization, photografting has been used in surface modification [330]. UV irradiation is used to extract active hydrogen atoms from the outer substrate surface and the surface free radicals initiate the in situ polymerization of the monomers attached to the substrate to form the surface grafted chains [330,363–365]. In comparison with other surface grafting approaches, photo- induced grafting has some advantages such as the low cost, simple equipment, mild reaction conditions, ease of industrial- ization, weak penetrability, and long-term stability of the grafted chains without affecting the bulk materials [322,366–370]. The photoinitiators are important in most photo-induced polymerization processes and benzophenone (BP) and its derivatives are most frequently used because they produce the highest grafting efficiency. Using this initiator, Ma et al. proposed a novel photo-induced living graft polymerization process consisting of two steps (Fig. 28) [364]. In the first step, in the absence of monomer solutions, the surface photoinitiators were produced by the combination of surface radicals and semipinacol radicals generated by BP abstracting hydrogen from the substrate. In the second step, graft polymerization was initiated by the surface initiators under UV irradiation after the monomer solution was added to the active substrate. During this process, initiator formation and graft polymerization occurred in different steps ensuring that they were independent and enabling independent control over the graft density and chain length of the graft polymer. This process also eliminated the formation of undesired homopolymers and crosslinked or branched polymers [364]. Although most photografting polymerization techniques require the addition of photoinitiators, some monomers have unique self-initiating properties, for instance, the ability to undergo photografting polymerization without photoinitiators [371]. The typical monomers include styrene, maleic anhydride, acrylic acid, methacrylic acid, 2-hydroxyethyl acrylate, 216 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

Fig. 28. Schematic diagram of a novel photo-induced living graft polymerization method [364]. Copyright 2000. Adapted with permission from the American Chemical Society. and 2-hydroxyethyl methacrylate [366,372]. In addition, some polymeric substrates can produce semibenzopinacol- containing BP radicals upon photo-irradiation. For example, Kyomoto et al. conducted photo-initiated polymerization of MPC onto poly(ether-ether-ketone) (PEEK) in the absence of photoinitiators to improve the surface properties [373]. Because MPC is a highly hydrophilic compound, the water wettability and lubricity of the PMPC-grafted PEEK surface were consid- erably enhanced compared to the untreated PEEK surface. It was further improved as the photo-irradiation increased as shown in Figs. 29 and 30, respectively [373]. During photo-irradiation, a nanometer-scale PMPC layer formed on the surface and became thicker with time (Fig. 31) and the amount of BSA adsorbed on the PMPC-grafted PEEK surface decreased with time extends compared to the untreated PEEK (Fig. 32). As shown in Table 5 [363,364,369,371,373–394], different monomers are selected for different substrates during photo- induced grafting polymerization. For example, MMA, N-vinyl-2-pyrrolidone (NVP), AA, and AAm are frequently used as monomers in photo grafting modification of PP because the poor biocompatibility and bad hydrophilicity restrict biomedical applications despite the high void volumes, well-controlled porosity, and chemical inertness as microfiltration and ultrafil- tration membranes [363,364,374–377]. Yang and co-workers utilized the sugar-containing monomer D-gluconamidoethyl methacrylate (GAMA) to modify the surface of PP in UV-induced photografting polymerization to improve the surface hydrophilicity and hemocompatibility [374]. As shown in Fig. 33 [374], the static, advancing, and receding contact angles decreased with the degree of GAMA grafting, indicating the improvement of the surface hydrophilicity by grafting GAMA. The number of adhered platelets decreased as the degree of GAMA grafting increased and in the case of the higher degree of GAMA grafting (4.72 and 6.28 wt%), the adhered platelets had almost the spherical shape, meaning that the surface did not activate the platelets so that the hemocompatibility was improved (Fig. 34) [374]. In addition to biocompatibility, the anti-bacterial polyvinyl-pyrrolidone-iodine complexes could be grafted onto the surface of the PP film to improve its

Fig. 29. Static-water contact angle (n = 15) of PMPC-grafted PEEK as a function of the photo-irradiation time with MPC concentrations of 0.25 and 0.50 mol/ L. Bar: Standard deviation [373]. Copyright 2010. Adapted with permission from Elsevier Science Ltd. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 217

Fig. 30. Coefﬁcient of dynamic friction (n = 5) of PMPC-grafted PEEK as a function of the photo-irradiation time with MPC concentrations of 0.25 and 0.50 mol/L. Bar: Standard deviation [373]. Copyright 2010. Adapted with permission from Elsevier Science Ltd.

Fig. 31. Cross-sectional TEM images of PMPC-grafted PEEK obtained with a MPC concentration of 0.5 mol/L and various photo-irradiation times. Bar: 100 nm [373]. Copyright 2010. Adapted with permission from Elsevier Science Ltd. antibacterial performance and the products exhibited clear anti-bacterial activity with a broad spectrum and high efficiency (Fig. 35) [375]. Polydimethylsiloxane (PDMS)-based materials are promising materials in ophthalmologic applications, microfluidic devices, artificial lungs and artificial finger joints due to the high oxygen permeability, convenient processability, good mechanical properties, optical transparency, self-sealing properties, and chemical stability [380,381]. In spite of these advan- 218 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

Fig. 32. Amount of adsorbed BSA (n = 3) of PMPC-grafted PEEK as a function of the photo-irradiation time with MPC concentrations of 0.25 and 0.50 mol/L. Bar: Standard deviation [373]. Copyright 2010. Adapted with permission from Elsevier Science Ltd.

Table 5 Biomaterial grafted with bioactive polymers through photo-induced graft polymerization.

Substrate Monomer Ref. PP MMA, NVP, AA, AAm, GAMA [363,364,374–377] PEEK MPC [373] PDMS AA, PEGMA, PEGDA, MPC [378–380] PE MPC, AA [382–384] PCL NVP, MAA [385,386] PLLA NVP [385] PLGA NVP [385] PLA AA, AAm [369] SEBS NVP [371] PES AA, HEMA, EDA [387] PVDF AA, HEMA. EDA [388] PU AAm [393] PCU PEGMA [394] Silicon wafer MMA, St, MA, NIPAM, HEMA, AAm [389–391] Porous polymer monolith PEGMA [392]

Fig. 33. Comparison of advancing contact angle (AC), receding contact angle (RC), and statistic contact angle (SC) on the nascent and modiﬁed PPMMs: (1)– (7) 0, 1.52, 2.58, 3.79, 4.72, 5.76, and 6.28 wt% GAMA grafted PPMMs, respectively [374]. Copyright 2005. Adapted with permission from the American Chemical Society. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 219

Fig. 34. Scanning electron micrographs of adhered platelets on the nascent and modiﬁed PPMMs: (a)–(d) 0, 1.52, 4.72, and 6.28 wt% GAMA-grafted PPMMs, respectively (left 2500, right 10,000) [374]. Copyright 2005. Adapted with permission from the American Chemical Society.

tages, PDMS still requires further modification because of its inherent hydrophobicity and susceptibility to biofouling. Sugiura et al. applied photo-induced graft polymerization to micropatterned surface modification of PDMS with polyethylene glycol diacrylate (PEGDA) [379]. As shown in Fig. 36, the green fluorescence intensity was proportional to the amount of adsorbed BSA, indicating that the untreated PDMS area adsorbed more protein than the PEGDA-grafted area. That is, the 220 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

Fig. 35. Change of the viable cell number of E. coli, S. aureus, and C. albicans after contact with the virgin and modified film surfaces for different times. E. coli⁄, S. aureus⁄, C. albicans⁄”: the microorganisms contacting with the virgin films [375]. Copyright 2005. Adapted with permission from Wiley Periodicals, Inc.

PEGDA-grafted layer prevented non-specific protein adsorption on PDMS [379]. PDMS could also be imparted with biological functions by photo grafting other monomers such as MPC [380]. The cell adhesion behavior could be tailored by this method and as shown in Fig. 37 the HepG2 cells were observed to attach to the gelatin-adsorbed area and not to the PEG-covered area. The wear resistance of some biopolymers can be improved by photo grafting techniques. As the important component in the bearing couple of artificial joints, ultra-high molecular weight polyethylene (UHMWPE) releases wear debris at the interface between the implant and surrounding tissues during contact with the metal femoral component under a load usually inducing osteolysis. Minimizing the formation of wear particles from UHMWPE is the best way to prevent osteolysis. Deng et al. grafted AA onto UHMWPE by photo-induced radical graft polymerization. The wear rate of the untreated UHMWPE was higher than that of modified UHMWPE in saline, distilled water, and calf serum lubricant and the modified UHMWPE grafted with 3.5% showed the smallest wear rate which was just quarter that of the untreated sample (Fig. 38) [382]. Another common acetabular material is cross-linked polyethylene (CLPE) because of its excellent anti-wear properties [383–384]. Kyomoto and co-workers proposed an artificial hip joint system with the MPC polymer grafted onto the surface of CLPE (CLPE-g-MPC) by UV irradiation at 5 mW/cm2 for 10–360 min at 60 °C [383]. As shown in Table 6 [383], the physical and mechanical properties of the CLPE and CLPE-g-MPC changed little but the friction coefficient of CLPE-g-MPC decreased shar- ply by 88% compared to the untreated CLPE [383]. Generally, tissue regeneration or reconstruction requires high affinity between the materials and surrounding tissues or cells. Next-generation materials must be ‘‘smart” to induce cell growth and differentiation. Photo-induced surface grafting can play this role in some polymeric materials. For example, biodegradable PCL can be used in drug delivery systems, tissue-engineered skin, and scaffolds to foster the growth of fibroblasts and osteoblasts. However, PCL is hydrophobic and T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 221

Fig. 37. Optical micrographs of HepG2 cells cultured on the micropatterned- PEGDA-grafted PDMS observed through a 4 objective lens (a) and a 10 objective lens (b) [379]. Copyright 2008. Adapted with permission from Elsevier B.V.

unfavorable to cell growth. Zhu et al. grafted PMAA and gelatin onto PCL under UV irradiation and as shown in Fig. 39, the PCL membrane modiﬁed with PMAA or gelatin exhibited improved cytocompatibility with human ECs [386]. Similarly, NVP 222 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

Properties CLPE CLPE-g-MPC Physical properties Density (g/cm3) 0.944 (0.002) 0.943 (0.001) Swelling ratio 2.99 (0.11) 2.94 (0.10) Network chain density (103°mol/ml) 0.437 (0.043) 0.459 (0.044) M.W. between Cross-links (g/mol) 2165 (214) 2069 (186) Cross-link density (mol%) 0.65 (0.06) 0.68 (0.07) Mechanical properties Yield strength (MPa) 23.2 (0.4) 23.1 (0.5) Impact strength (kJ/m2) 75.0 (1.4) 77.0 (1.9) Creep deformation (%) 0.89 (0.17) 0.63 (0.40) Hardness (shore D) 68.2 (0.9) 68.4 (0.5) Tribological properties Friction coefﬁcient 0.0075 0.0009 Wear rate (mg/106 cycles) 3.12 1.43

The standard deviation is in parenthese.

Fig. 39. The cell morphology after cultured for 4 d on TCPS (a), PCL-g-PMAA with WCA 69.91 (b) and PCL-g-PMAA-gelatin with WCA 62.61 (c), respectively. (1) refers to higher magniﬁcation while (2) to an overview under SEM with the same sample. Cell seeding density 15 104 cm2. (TCPS: tissue culture polystyrene, WCA: water contact angle) [386]. Copyright 2002. Adapted with permission from Elsevier Science Ltd.

was covalently grafted onto PCL, PLLA, and poly(lactide-co-glycolide) (PLGA) under irradiation to produce a bioactive surface favoring adhesion, growth, and proliferation of normal human cells [278]. In addition to the aforementioned polymer substrates, there are other polymer substrates such as poly(lactic acid) (PLA) [369], poly(styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS) [371], polyethersulfone (PES) [387], poly(vinylidene ﬂuo- ride) (PVDF) [388],PU[393], polycarbonateurethane (PCU) [394], and inorganic substrates such as silicon wafer [389– 391]. Photo-induced graft polymerization can be combined with ATRP [395] and NMP [396]. The combined method provides a straightforward way to prepare block or comb-like copolymers with a controlled architecture [395,396]. Despite the aforementioned advantages, photo-induced graft polymerization should be further improved [366]. There is still no direct technique to characterize parameters such as the length of the grafted chains and their distribution, nature of the branched or superbranched graft polymer chains, and crosslinking structure. These parameters are important to the effectiveness of the process. There are other problems associated with the reproducibility of grafting, degradation, and rear- rangement. Owing to high-energy ion bombardment or UV radiation, most polymers undergo inevitable degradation. Rear- rangement of the grafted functional groups can lead to substrate degradation common to both plasma- and photo-induced grafting polymerization. The last problem is the microenvironmental effect. Because the polymer chains covalently grafted onto the substrate should behave differently than the free polymer chains in the solution or bulk, the performances of the grafted layers should be experimentally examined and compared with the corresponding free polymer chains. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 223

6. Biocompatibility of polymerized surfaces

Since biomaterials are in direct contact with the biological media, the surface must be biocompatible, that is, not inducing adverse response from the body. Williams proposed the definition of biocompatibility as the ability of a material to perform with an appropriate host response in a specific application [397]. Therefore, the suitability of these polymers after surface polymerization must be assessed in terms of the potential toxicity and detrimental effects in the physiological environment besides the biological performance of the biomaterials. In general, implanted biomaterials often induce a foreign body reaction consisting of three steps starting with adsorption of nonspecific proteins onto the surface of implants, followed by attachment of different types of cells onto the surface inducing up-regulation of cytokines and subsequent pro- inflammatory processes, and finally formation of giant cells and cytokine release [398]. The biocompatibility of polymerized surfaces is often evaluated by cytotoxicity and blood compatibility closely related to protein adsorption and platelets adhesion in vitro and in vivo [399].

6.1. Cytotoxicity

The cytotoxicity of polymerized surfaces is determined by the nature of the polymers including molecular weight, charge density, type of cationic functionalities, structure, and sequence (i.e. block, random, linear, branched, and conformational ﬂexibility) [400]. Chen et al. reported that cationic dendrimers were more cytotoxic than anionic or PEGylated dendrimers [401] and Li et al. disclosed that quaternized polyamidoamine (PAMAM)-OH derivatives displayed lower cytotoxicity than

PAMAM-NH2 due to the shielding of the internal cationic charges by surface hydroxyl groups [402]. By means of in vitro incu- bation with HEP G2 cells or 293 human embryonic kidney cells, it was found that the increased charge density and molecular weight increased the toxicity of PAMAM after modifying the surface of PAMAM with lysine or arginine [403]. Scarioti et al. found that the surface charge could be controlled by in situ polymerization of AA on cationic liposomes by changing the concentration of PAA and adjusting the cytotoxicity of cationic liposomes. In their experiments, completely coated liposomes exhibited better mouse ﬁbroblasts viability [404]. On the polymerized surface, direct contact with negatively-charged cell membrane proteins and phospholipids with cationic polymers disturbed the membrane structure and functions due to ery- throcyte lysis [405,406]. Polymerization of PLLA, PAA or PHEMA on biomaterials not only modulated the surface hydrophilicity but also provided functional groups for surface bioconjugation consequently offering a more favorable biological environment for cell adhesion and growth on the surface on inorganic [407] and organic substrates [408]. Multihydroxyl hyperbranched polyglycerol (HPG) had good biocompatibility. It could decrease the cytotoxicity of CdTe quantum dots (QDs) indicating that surface polymerization of biocompatible dendritic polymers could be employed to obtain robust nontoxic functionalized QDs [409]. Other polycations polymers like diethylaminoethyl (DEAE)-dextran [400], PLL [405], dendrimers [410] and PEI [411] also exhibited increasing cytotoxicity as a function of molecular weights but it was applicable to polymers with different structures. For instance, Fischer et al. showed that poly(l-lysine hydro bromide (PLL) with 36.6 kDa inﬂuenced the cell viability more than cationized human serum albumin (cHSA) with 67 kDa and the 500 kDa DEAE-dextran [400].

6.2. Hemocompatibility

Protein adsorption plays a crucial role in vivo pertaining to the initial formation of thrombus at the blood-material interface because it is the initial contact between blood and biomaterials that determines subsequent platelet adhesion and activation [412]. Hence, control of protein adsorption is crucial to the design of surface polymerization. Yuan et al. employed ATRP to obtain block copolymers with various compositions comprising of PMPC and poly(3-methacryloxypropyl trimethoxysilane) (PMTSi) segments as coatings on cellulose membranes (CMs) [413]. The surface properties such as the surface contact angle, surface morphology, and number of functional phosphorylcholine groups were changed by controlling the density of the functional MPC by adjusting the ratio of the two monomers (MPC and MTSi) and their results disclosed that protein adsorption depended on the MPC density and PMPC chain length [413]. The surface grafted polyethylene (g- PE) films with different types of water soluble polymers such as PMPC, poly[2-(glucosyloxy)ethyl methacrylate] (PGEMA), poly(N-isopropylacrylamide) (PNIPAM) and poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) exhibited different hemocompatibility, and PMPC-g-PE film showed the best biocompatibility among the g-PE films because its surface adsorbed less protein than the untreated PE and other g-PE films. Consequently, it showed the highest inhibitory effect of thrombin activity among the water soluble polymers due to the formation of a hydrogel structure by the PMPC segments [412]. The MPC moi- ety was believed to have a weak interaction with water molecules and a small surface active ability [412]. The chain length, molecular weight, and density of the grafted polymers on the biomaterials also affect platelet adhesion. For insistence, Feng et al. conducted ultraviolet initiated photopolymerization to immobilize poly(ethylene glycol) monoacrylates (PEGMAs) with molecular weights between 400 and 1000 g mol1 onto PCU to increase the hydrophilicity and improve the hemocompatibility [394]. The surface-grafted films were hydrophilic and the brush-like structure of the PEG chains resisted platelet adsorption more than the unmodified film. The PCU-g-PEGMA with 800 g mol1 exhibited the lowest platelet adsorption and best hemocompatibility. It might be ascribed to the optimal balance between the PEGMA immobilization density and PEG chain length as well as the well distributed brush structure with a more homogenous topography [394]. In the case of 224 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 the polypropylene non-woven (NWFPP) membrane modified by 2-acrylamido-2-methylpropane sulfonic acid (AMPS) by the

O2 plasma pretreatment and UV-induced photografting, the hydrophilicity of the membranes increased with grafting densities of the poly(AMPS) from 0 to 884.2 g cm2 and protein adsorption decreased with grafting densities of poly(AMPS). There is reduction in the number of platelets adhering to the modified membrane compared to the unmodified membrane attributable to incorporation of anionic sulfonic acid groups into the membrane surface due to repulsion with the negatively- charged platelets [414]. Similarly, polymers such as hyaluronic acid (HA) can be used as the polymerization source to resist platelet adhesion and improve cell-substrate interactions [415]. In practice, biocompatibility depends on many reasons. With regard to surface polymerized biomaterials, the physiological environment typically induces abrasion, corrosion, or degradation of the polymers in turn influencing the host response. The biomaterials should be sterilized before clinical use by methods such as high-temperature sterilization, radiation by gamma ray and electron beams, chemical sterilization, and so on. In the biological environment, adsorption of water can change the properties of surface polymers. During sterilization, the high temperature and radiation can alter the performance of the biopolymers. For example, polyesters easily degrade when exposed to water due to the formation of oligomers which may invoke inflammation in the body [398]. Another problem is that the excess heat produced during polymerization from exothermic reactions may influence the behavior of cells and tissues [411]. In addition, the volume expansion or shrink- age as a result of the heating may contribute to interfacial failure between the biopolymers and tissues.

6.3. Manipulation of cell behaviors

Apart from the aformentioned cytocompatibility and hemocompatibility, next-generation biomaterials have been endow- ing some ‘‘smart” biological functions, i.e., precise manipulation of cell behaviors according to the desired setting to accel- erate the tissue repair or reconstruction or through the specific surface design, which will be required and incorporated into the concept of biocompatibility in near future. Due to their similar molecule structures to the basic organization of natural tissues, some peptide ligands such as arginine-glycine-aspartic acid (RGD) [416] and Arg-Glu-Asp-Val (REDV) [417] have been employed to modify the surface of biomaterials to mimic the natural extracellular matrix (ECM), and thus to regulate the cell adhesion [418]. It has been demonstrated that the density and conformational changes of peptides, and as well as the coupling strength between the peptide and the substrate can regulate cell behaviors [419–421]. Chollet et al. investigated the behaviors of different types of cells on the PET substrates modified by the covalent grafting of different densities of RGD containing peptides (varying between 0.6 and 2.4 pmol/mm2), and their cell attachment assays showed that a minimal RGDC peptide density was 1 pmol/mm2 for improving the osteoblastic cells (MC3T3) and endothelial cells (HSVEC) responses [419]. The number of focal contacts ciould be enhanced by increasing the grafted RGDC density on PET, and the largest number of adherent MC3T3 and HSVEC could be observed on RGDC-modified PET with a RGD density of 2.4 and 1.7 pmol/mm2, respectively [419]. These results disclosed that the density of peptides immobilized on the surface of biomaterials was an important parameter influencing the cell behaviors. Recently, an electrically switchable surface was fabricated, which relied on electrically-induced conformational changes within surface-grafted RGD oligopeptides as the means of modulating cell adhesion (Fig. 40) [420]. The charged backbone of the oligopeptide has been proved that it can be potentially harnessed to induce its folding on the surface upon an application of an electrical potential [422,423]. The RGD modified surface was comprised of a mixed self-assembled monolayer (SAM) consisting of two components: an oligopeptide with three lysine residues and a glycine-arginine-glycine-aspartate-ser ine (GRGDS), and an ethylene glycol-terminated thiol (C11TEG) [420]. The results showed that conformational changes could dynamically regulate cell adhesion by selectively exposing under open circuit (OC) conditions (bio-active state) or concealing under negative potential (bio-inactive state) the RGD to the cell [420]. Bian and co-workers developed a facile platform to inves-

Fig. 40. Schematic of the dynamic RDG oligopeptide SAM utilized for controlling speciﬁc cellular interactions. The electrically switchable SAM exposes the RGD peptide and supports cell adhesion under open circuit (OC) conditions (no applied potential), while under an applied negative potential the RGD is concealed, inhibiting cell adhesion [420]. Copyright 2014. Adapted with permission from the Royal Society of Chemistry. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 225

Fig. 41. Representative fluorescence micrographs of the hMSCs cultured on LCS0.5, LCS12.5, HCS25, and HCS50 for 24 h. Coverslips treated with piranha only is used as the control for all the cell experiments. High-magnification images are taken to show the morphological feature of cells grown on the fabricated surfaces. Scale bar is 100 lm [421]. Copyright 2015. Adapted with permission from the American Chemical Society. tigate the effects of varied coupling strength between the RGD peptide and the glass substrate on stem cell behaviors, where the coupling strength of an integrin-binding ligand RGD was controlled solely by electrostatic interactions between the positively charged aminated glass surface and the negatively charged citrate-capped gold nanoparticles (cit-AuNPs) [421]. A total of 0.5% and 12.5% of (3-aminopropyl) triethoxysilane (APTES) were used to fabricate low-coupling-strength surfaces (namely, LCS0.5 and LCS12.5), whereas 25% and 50% of APTES were used to fabricate high-coupling-strength surfaces (namely, HCS25 and HCS50). It revealed that human mesenchymal stem cells (hMSCs) grown on both LCS0.5 and LCS12.5 surfaces were highly elongated and spindle like in shape, while hMSCs were widely spread on both HCS surfaces, especially for cells grown on LCS50 (Fig. 41), which suggested that the coupling strength of the RGD peptide on the substrate could modulate the adhesion, spreading, and differentiation of hMSCs [421]. Besides peptides, there are some other polymers that can be grafted onto the surface of biomaterials to control cell behaviors, such as PAA [424], PAAm [425], PNIPAAm [426], and poly(3-sulfopropylmethacrylate) (PSPMA) [427]. The graft density of polymers can also regulate cell behaviors [424,425]. For example, different density of ACOOH was introduced on PEEK surface using plasma polymerization of AA, and the results exhibited that the adhesion and proliferation of pre- osteoblasts decreased with increasing ACOOH surface density, whereas the spreading of pre-osteoblasts increased with increasing ACOOH surface density [424]. Lilge and Schönherr investigated the effects of varied graft density of PAAm prepared by surface-initiated atom transfer radical polymerization (SI-ATRP) on cell attachment and spreading, and their results displayed that cells attached only on low density PAAm brushes, while polymer brushes with higher grafting density remained cell resistant [425]. The nanoarchitectonics of PNIPAAm brushes could also influence cell adhesion behavior [426]. Amin and co-workers reported the exploitation of directly photografting polymer on polydopamine (PDA) nanosheets for controlling cell adhesion [427]. Cells grew and spread over the as-grafted PDA layer, while about 44% more cells grew, attached and spread on a PDA nanosheet compared to as-grafted PDA layer, which indicated that PDA nanosheet promoted more cells growth and attachment [427]. Furthermore, after grafting negatively charged polymer brush such as PSPMA on a PDA nanosheet, significantly fewer cells grown on PSPMA carpet, which suggested that the PSPMA carpet inhibited cell growth and attachment [427].

7. Conclusion and outlook

Recent advances in surface engineering and biomaterials enable functionalization by polymer grafting techniques to improve the biological functions at the interface between tissues/cells and biomaterials. This review summarizes the common grafting techniques with a focus on controlled/living radical polymerization (CLRP), a rapidly developing technique that yields polymers with controlled molecular weight and low polydispersities. Of the three main approaches, NMP, ATRP and RAFT polymerization, NMP is developed ﬁrst but ATRP and RAFT are the most common methods in surface polymeriza- 226 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 tion of biomaterials. Recently developed methods for surface functionalization of biomaterials such as plasma-induced graft polymerization, radiation-induced graft polymerization, and photo-induced graft polymerization are described. Although grafting polymerization methods are promising tools to enhancing surface biological functions such as antibacterial activity and bioactivity, more investigations are needed in order to fathom the mechanisms and realize their full potential. For example, future work should focus on achieving precise control of grafting onto different types of substrates with different shape, understanding the relationship between speciﬁc biological functions and grafted molecular architectures on the surface, and achieving multi-functionalities by simultaneous grafting of different molecules.

Acknowledgements

This work is jointly supported by Special Prophase Program for Key Basic Research of the Ministry of Science and Tech- nology of China (973 Program) No. 2014CB660809, the National Natural Science Foundation of China, Nos. 51422102 and 81271715, Hong Kong Research Grants Council (RGC) General Research Funds (GRF) Nos. 112212 and 11301215, as well as Hubei Provincial Natural Science Foundation (China) Nos. 2013CFA018 and 2014CFB551.

References

[1] Stupp SI, Braun PV. Molecular manipulation of microstructures: biomaterials, ceramics, and semiconductors. Science 1997;277:1242–8. [2] Ratner BD, Bryant SJ. Biomaterials: where we have been and where we are going. Annu Rev Biomed Eng 2004;6:41–75. [3] Liu X, Chu PK, Ding C. Surface modification of titanium, titanium alloys, and related materials for biomedical applications. Mater Sci Eng R 2004;47:49–121. [4] Gorbet MB, Sefton MV. Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes. Biomaterials 2004;25:5681–703. [5] Furie B, Furie BC. Thrombus formation in vivo. J Clin Invest 2005;115:3355–62. [6] Horbett TA. Principles underlying the role of adsorbed plasma proteins in blood interactions with foreign materials. Cardiovasc Pathol 1993;2:137–48. [7] Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med 2004;351:1645–54. [8] Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med 2004;350:1422–9. [9] Rohde H, Burandt EC, Siemssen N, Frommelt L, Burdelski C, Wurster S, et al. Polysaccharide intercellular adhesin or protein factors in biofilm accumulation of Staphylococcus epidermidis and Staphylococcus aureus isolated from prosthetic hip and knee joint infections. Biomaterial 2007;28:1711–20. [10] Wu S, Liu X, Yeung KWK, Liu C, Yang X. Biomimetic porous scaffolds for bone tissue engineering. Mater Sci Eng R 2014;80:1–36. [11] Dalby MJ, Gadegaard N, Tare R, Andar A, Riehle MO, Herzyk P, et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater 2007;6:997–1003. [12] Wu S, Liu X, Hu T, Chu PK, Ho JPY, Chan YL, et al. A biomimetic hierarchical scaffold: natural growth of nanotitanates on three-dimensional microporous Ti-based metals. Nano Lett 2008;8:3803–8. [13] Jeon H, Hidai H, Hwang DJ, Healy KE, Grigoropoulos CP. The effect of micronscale anisotropic cross patterns on fibroblast migration. Biomaterials 2010;31:4286–95. [14] Itoh S, Kikuchi M, Koyama Y, Takakuda K, Shinomiya K, Tanaka J. Development of an artificial vertebral body using a novel biomaterial, hydroxyapatite/collagen composite. Biomaterials 2002;23:3919–26. [15] Bhattacharya A, Misra BN. Grafting: a versatile means to modify polymers techniques, factors and applications. Prog Polym Sci 2004;29:767–814. [16] Minko S. Grafting on solid surfaces: ‘‘grafting to” and ‘‘grafting from” methods. Polym Surf Interfaces 2008:215–34. [17] Zhao B, Brittain WJ. Polymer brushes: surface-immobilized macromolecules. Prog Polym Sci 2000;25:677–710. [18] Xu FJ, Neoh KG, Kang ET. Bioactive surfaces and biomaterials via atom transfer radical polymerization. Prog Polym Sci 2009;34:719–61. [19] Edmondson S, Osborne VL, Huck WTS. Polymer brushes via surface-initiated polymerizations. Chem Soc Rev 2004;33:14–22. [20] Gupta S, Agrawal M, Uhlmann P, Simon F, Stamm M. Poly(N-isopropyl acrylamide)-gold nanoassemblies on macroscopic surfaces: fabrication, characterization, and application. Chem Mater 2010;22:504–9. [21] Brittain WJ, Minko S. A structural definition of polymer brushes. J Polym Sci Part A Polym Chem 2007;45:3505–12. [22] Ito Y, Ochiai Y, Park YS, Imanishi Y. PH-sensitive gating by conformational change of a polypeptide brush grafted onto a porous polymer membrane. J Am Chem Soc 1997;119:1619–23. [23] Luzinov I, Julthongpiput D, Tsukruk VV. Thermoplastic elastomer monolayers grafted to a functionalized silicon surface. Macromolecules 2000;33:7629–38. [24] Luzinov I, Julthongpiput D, Malz H, Pionteck J, Tsukruk VV. Polystyrene layers grafted to epoxy-modified silicon surfaces. Macromolecules 2000;33:1043–8. [25] Minko S, Patil S, Datsyuk V, Simon F, Eichhorn KJ, Motornov M, et al. Synthesis of adaptive polymer brushes via ‘‘grafting to” approach from melt. Langmuir 2002;18:289–96. [26] Lemieux M, Minko S, Usov D, Stamm M, Tsukruk VV. Direct measurement of thermoelastic properties of glassy and rubbery polymer brush nanolayers grown by ‘‘grafting-from” approach. Langmuir 2003;19:6126–34. [27] Bialk M, Prucker O, Rühe J. Grafting of polymers to solid surfaces by using immobilized methacrylates. Colloids Surf A 2002;198:543–9. [28] Lemieux M, Usov D, Minko S, Stamm M, Shulha H, Tsukruk VV. Reorganization of binary polymer brushes: Reversible switching of surface microstructures and nanomechanical properties. Macromolecules 2003;36:7244–55. [29] Motornov M, Minko S, Eichhorn KJ, Nitschke M, Simon F, Stamm M. Reversible tuning of wetting behavior of polymer surface with responsive polymer brushes. Langmuir 2003;19:8077–85. [30] Berger S, Synytska A, Ionov L, Eichhorn KJ, Stamm M. Stimuli-responsive bicomponent polymer Janus particles by ‘‘grafting from”/‘‘grafting to” approaches. Macromolecules 2008;41:9669–76. [31] Coessens V, Pintauer T, Matyjaszewski K. Functional polymers by atom transfer radical polymerization. Prog Polym Sci 2001;26:337–77. [32] Hawker CJ, Bosman AW, Harth E. New polymer synthesis by nitroxide mediated living radical polymerizations. Chem Rev 2001;101:3661–88. [33] Otsu T. Iniferter concept and living radical polymerization. J Polym Sci Part A Polym Chem 2000;38:2121–36. [34] Pyun J, Matyjaszewski K. Synthesis of nanocomposite organic/inorganic hybrid materials using controlled/‘living’ radical polymerization. Chem Mater 2001;39:3436–48. [35] Qui J, Charleux B, Matyjaszewski K. Controlled/living radical polymerization in aqueous media: homogeneous and heterogeneous systems. Prog Polym Sci 2001;26:2083–134. [36] Cunningham MF. Living/controlled radical polymerizations in dispersed phase systems. Prog Polym Sci 2002;27:1039–67. [37] Matyjaszewski K, Spanswick J. Controlled/living radical polymerization. Mater Today 2005;8:26–33. [38] Cunningham MF. Living/controlled radical polymerizations in aqueous dispersed systems. Prog Polym Sci 2008;33:365–98. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 227

[39] Matyjaszewski K. Macromolecular engineering: from rational design through precise macromolecular synthesis and processing to targeted macroscopic material properties. Prog Polym Sci 2005;30:858–75. [40] Hadjichristidis N, Iatrou H, Pitsikalis M, Mays J. Macromolecular architectures by living and controlled/living polymerizations. Prog Polym Sci 2006;31:1068–132. [41] Braunecker WA, Matyjaszewski K. Controlled/living radical polymerization: features, developments, and perspectives. Prog Polym Sci 2007;32:93–146. [42] Barbey R, Lavanant L, Paripovic D, Schüwer N, Sugnaux C, Tugulu S, et al. Polymer brushes via surface-initiated controlled radical polymerization: synthesis, characterization, properties, and applications. Chem Rev 2009;109:5437–527. [43] Goto A, Fukuda T. Kinetics of living radical polymerization. Prog Polym Sci 2004;29:329–85. [44] Angot S, Murthy S, Taton D, Gnanou Y. Atom transfer radical polymerization of styrene using a novel octafunctional initiator: synthesis of well- defined polystyrene stars. Macromolecules 1998;31:7218–25. [45] Mayadunne RTA, Jeffery J, Moad G, Rizzardo E. Living free radical polymerization with reversible addition-fragmentation chain transfer (RAFT polymerization): approaches to star polymers. Macromolecules 2003;36:1505–13. [46] Yu WH, Kang ET, Neoh KG. Controlled grafting of comb copolymer brushes on poly(tetrafluoroethylene) films by surface-initiated living radical polymerizations. Langmuir 2005;21:450–6. [47] Mori H, Böker A, Krausch G, Müller AHE. Surface-grafted hyperbranched polymers via self-condensing atom transfer radical polymerization from silicon surfaces. Macromolecules 2001;34:6871–82. [48] Mori H, Seng DC, Zhang M, Müller AHE. Hybrid nanoparticles with hyperbranched polymer shells via self-condensing atom transfer radical polymerization from silica surfaces. Langmuir 2002;18:3682–93. [49] Liu B, Kazlauciunas A, Guthrie J, Perrier S. One-pot hyperbranched polymer synthesis mediated by reversible addition fragmentation chain transfer (RAFT) polymerization. Macromolecules 2005;38:2131–6. [50] Toomey R, Freidank D, Rühe J. Swelling behavior of thin, surface-attached polymer networks. Macromolecules 2004;37:882–7. [51] Stuart MAC, Huck WT, Genzer J, Müller M, Ober C, Stamm M, et al. Emerging applications of stimuli-responsive polymer materials. Nat Mater 2010;9:101–13. [52] Oh JK, Tang C, Gao H, Tsarevsky NV, Matyjaszewski K. Inverse miniemulsion ATRP: a new method for synthesis and functionalization of well-defined water-soluble/crosslinked polymeric particles. J Am Chem Soc 2006;128:5578–84. [53] Lepoittevin B, Perrot X, Masure M, Hemery P. New route to synthesis of cyclic polystyrenes using controlled free radical polymerization. Macromolecules 2001;34:425–9. [54] Wannemacher T, Braun D, Pfaendner R. Novel copolymers via nitroxide mediated controlled free radical polymerization of vinyl chloride. Macromol Symp 2003;202:11–23. [55] Sciannamea V, Jérôme R, Detrembleur C. In-situ nitroxide-mediated radical polymerization (NMP) process: their understanding and optimization. Chem Rev 2008;108:1104–26. [56] Georges MK, Veregin RPN, Kazmaier PM, Hamer GK. Narrow molecular weight resins by a free-radical polymerization process. Macromolecules 1993;26:2987–8. [57] Hawker CJ. Molecular weight control by a ‘‘living” free-radical polymerization process. J Am Chem Soc 1994;116:11185–6. [58] Hawker CJ, Barclay GG, Orellana A, Dao J, Devonport W. Initiating systems for nitroxide-mediated ‘‘living” free radical polymerizations: synthesis and evaluation. Macromolecules 1996;29:5245–54. [59] Parvole J, Laruelle G, Khoukh A, Billon L. Surface initiated polymerization of poly(butyl acrylate) by nitroxide mediated polymerization: first comparative polymerization of a bimolecular and a unimolecular initiator-grafted silica particles. Macromol Chem Phys 2005;206:372–82. [60] Fischer H. The persistent radical effect: a principle for selective radical reactions and living radical polymerizations. Chem Rev 2001;101:3581–610. [61] Ananchenko GS, Souaille M, Fischer H, Mercier CL, Tordo P. Decomposition of model alkoxyamines in simple and polymerizing systems. II. Diastereomeric N-(2-methylpropyl)-N-(1-diethyl-phosphono-2,2-dimethylpropyl)-aminoxyl-based compounds. J Polym Sci Part A Polym Chem 2002;40:3264–83. [62] Ananchenko GS, Fischer H. Decomposition of model alkoxyamines in simple and polymerizing systems. I. 2,2,6,6-tetramethylpiperidinyl-n-oxyl- based compounds. J Polym Sci Part A Polym Chem 2001;39:3604–21. [63] Nicolas J, Guillaneuf Y, Lefay C, Bertin D, Gigmes D, Charleux B. Nitroxide-mediated polymerization. Prog Polym Sci 2013;38:63–235. [64] Liu K, Jiang L. Metallic surfaces with special wettability. Nanoscale 2011;3:825–38. [65] Zheng YF, Gu XN, Witte F. Biodegradable metals. Mater Sci Eng R 2014;77:1–34. [66] Ignatova M, Voccia S, Gilbert B, Markova N, Mercuri PS, Galleni M, et al. Synthesis of copolymer brushes endowed with adhesion to stainless steel surfaces and antibacterial properties by controlled nitroxide-mediated radical polymerization. Langmuir 2004;20:10718–26. [67] Voccia S, Jérôme C, Detrembleur C, Leclère P, Gouttebaron R, Hecq M, et al. Controlled free radical polymerization of styrene initiated from alkoxyamine attached to polyacrylate chemisorbed onto conducting surfaces. Chem Mater 2003;15:923–7. [68] Vallet-Regí M, Ruiz-Hernández E. Bioceramics: from bone regeneration to cancer nanomedicine. Adv Mater 2011;23:5177–218. [69] Soler-Illia GJAA, Sanchez C, Lebeau B, Patarin J. Chemical strategies to design textured materials: from microporous and mesoporous oxides to nanonetworks and hierarchical structures. Chem Rev 2002;102:4093–138. [70] Li Y, Shi J. Hollow-structured mesoporous materials: chemical synthesis, functionalization and applications. Adv Mater 2014;26:3176–205. [71] Tang F, Li L, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater 2012;24:1504–34. [72] Piao Y, Burns A, Kim J, Wiesner U, Hyeon T. Designed fabrication of silica-based nanostructured particle systems for nanomedicine applications. Adv Funct Mater 2008;18:3745–58. [73] Slowing II, Trewyn BG, Giri S, Lin VSY. Mesoporous silica nanoparticles for drug delivery and biosensing applications. Adv Funct Mater 2007;17:1225–36. [74] Bartholome C, Beyou E, Bourgeat-Lami E, Chaumont P, Lefebvre F, Zydowicz N. Nitroxide-mediated polymerization of styrene initiated from the surface of silica nanoparticles. In situ generation and grafting of alkoxyamine initiators. Macromolecules 2005;38:1099–106. [75] Chevigny C, Gigmes D, Bertin D, Jestin J, Boué F. Polystyrene grafting from silica nanoparticles via nitroxide-mediated polymerization (NMP): synthesis and SANS analysis with the contrast variation method. Soft Matter 2009;5:3741–53. [76] Chevigny C, Gigmes D, Bertin D, Schweins R, Jestin J, Boué F. Controlled grafting of polystyrene on silica nanoparticles using NMP: a new route without free initiator to tune the grafted chain length. Polym Chem 2011;2:567–71. [77] Li D, Sheng X, Zhao B. Environmentally responsive hairy nanoparticles: mixed homopolymer brushes on silica nanoparticles synthesized by living radical polymerization techniques. J Am Chem Soc 2005;127:6248–56. [78] Jiang X, Zhong G, Horton JM, Jin N, Zhu L, Zhao B. Evolution of phase morphology of mixed poly(tert-butyl acrylate)/polystyrene brushes grafted on silica particles with the change of chain length disparity. Macromolecules 2010;43:5387–95. [79] Jiang X, Zhao B, Zhong G, Jin N, Horton JM, Zhu L, et al. Microphase separation of high grafting density asymmetric mixed homopolymer brushes on silica particles. Macromolecules 2010;43:8209–17. [80] Bao C, Tang S, Horton JM, Jiang X, Tang P, Qiu F, et al. Effect of overall grafting density on microphase separation of mixed homopolymer brushes synthesized from Y-Initiator-functionalized silica particles. Macromolecules 2012;45:8027–36. [81] Blas H, Save M, Boissière C, Sanchez C, Charleux B. Surface-initiated nitroxide-mediated polymerization from ordered mesoporous silica. Macromolecules 2011;44:2577–88.

[82] Wu S, Weng Z, Liu X, Yeung KWK, Chu PK. Functionalized TiO2 based nanomaterials for biomedical applications. Adv Funct Mater 2014;24:5464–81. 228 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

[83] Matsuno R, Otsuka H, Takahara A. Polystyrene-grafted titanium oxide nanoparticles prepared through surface-initiated nitroxide-mediated radical polymerization and their application to polymer hybrid thin ﬁlms. Soft Matter 2006;2:415–21. [84] Matsuno R, Otsuka H, Takahara A. Preparation of polystyrene brushes on titanium oxide surface by nitroxide-mediated radical polymerization. Polym Prepr 2005;46:357–8. [85] Matsuno R, Yamamoto K, Otsuka H, Takahara A. Polystyrene grafted magnetite nanoparticles prepared through surface-initiated nitroxyl-mediated radical polymerization. Chem Mater 2003;15:3–5. [86] Matsuno R, Yamamoto K, Otsuka H, Takahara A. Polystyrene- and poly(3-vinylpyridine)-grafted magnetite nanoparticles prepared through surface- initiated nitroxide-mediated radical polymerization. Macromolecules 2004;37:2203–9. [87] Kobayashi M, Matsuno R, Otsuka H, Takahara A. Precise surface structure control of inorganic solid and metal oxide nanoparticles through surface- initiated radical polymerization. Sci Technol Adv Mater 2006;7:617–28. [88] Binder WH, Gloger D, Weinstabl H, Allmaier G, Pittenauer E. Telechelic poly(N-isopropylacrylamides) via nitroxide-mediated controlled polymerization and ‘‘click” chemistry: livingness and ‘‘grafting-from” methodology. Macromolecules 2007;40:3097–107.

[89] Robbes A-S, Cousin F, Meneau F, Chevigny C, Gigmes D, Fresnais J, et al. Controlled grafted brushes of polystyrene on magnetic c-Fe2O3 nanoparticles via nitroxide-mediated polymerization. Soft Matter 2012;8:3407–18. [90] Karousis N, Tagmatarchis N, Tasis D. Current progress on the chemical modification of carbon nanotubes. Chem Rev 2010;110:5366–97. [91] Lou X, Detrembleur C, Pagnoulle C, Jérôme R, Bocharova V, Kiriy A, et al. Surface modification of multiwalled carbon nanotubes by poly(2- vinylpyridine): dispersion, selective deposition, and decoration of the nanotubes. Adv Mater 2004;16:2123–7. [92] Spitalsky Z, Tasis D, Papagelis K, Galiotis C. Carbon nanotube-polymer composites: chemistry, processing, mechanical and electrical properties. Prog Polym Sci 2010;35:357–401. [93] Datsyuk V, Guerret-Piécourt C, Dagréou S, Billon L, Dupin J-C, Flahaut E, et al. Double walled carbon nanotube/polymer composites via in-situ nitroxide mediated polymerisation of amphiphilic block copolymers. Carbon 2005;43:873–6. [94] Dehonor M, Masenelli-Varlot K, González-Montiel A, Gauthier C, Cavaillé JY, Terrones H, et al. Nanotube brushes: polystyrene grafted covalently on CNx nanotubes by nitroxide-mediated radical polymerization. Chem Commun 2005;42:5349–51. [95] Zhao X-D, Fan X-H, Chen X-F, Chai C-P, Zhou Q-F. Surface modification of multiwalled carbon nanotubes via nitroxide-mediated radical polymerization. J Polym Sci Part A Polym Chem 2006;44:4656–67. [96] Zhao X, Lin W, Song N, Chen X, Fan X, Zhou Q. Water soluble multi-walled carbon nanotubes prepared via nitroxide-mediated radical polymerization. J Mater Chem 2006;16:4619–25. [97] Nicolas J, Mantovani G, Haddleton DM. Living radical polymerization as a tool for the synthesis of polymer-protein/peptide bioconjugates. Macromol Rapid Commun 2007;28:1083–111. [98] Chenal M, Boursier C, Guillaneuf Y, Taverna M, Couvreur P, Nicolas J. First peptide/protein PEGylation with functional polymers designed by nitroxide- mediated polymerization. Polym Chem 2011;2:1523–30. [99] Möller M, Hentschel C, Chi L, Studer A. Aggregation behaviour of peptide-polymer conjugates containing linear peptide backbones and multiple polymer side chains prepared by nitroxide-mediated radical polymerization. Org Biomol Chem 2011;9:2403–12. [100] Dash M, Chiellini F, Ottenbrite RM, Chiellini E. Chitosan–A versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci 2011;36:981–1014. [101] Hua D, Deng W, Tang J, Cheng J, Zhu X. A new method of controlled grafting modification of chitosan via nitroxide-mediated polymerization using chitosan-TEMPO macroinitiator. Int J Biol Macromol 2008;43:43–7. [102] Lefay C, Guillaneuf Y, Moreira G, Thevarajah JJ, Castignolles P, Ziarelli F, et al. Heterogeneous modification of chitosan via nitroxide-mediated polymerization. Polym Chem 2013;4:322–8. [103] Zhao B. Synthesis of binary mixed homopolymer brushes by combining atom transfer radical polymerization and nitroxide-mediated radical polymerization. Polymer 2003;44:4079–83. [104] Zhao B, He T. Synthesis of well-defined mixed poly(methyl methacrylate)/polystyrene brushes from an asymmetric difunctional initiator-terminated self-assembled monolayer. Macromolecules 2003;36:8599–602. [105] Zhao B. A combinatorial approach to study solvent-induced self-assembly of mixed poly(methyl methacrylate)/polystyrene brushes on planar silica substrates: effect of relative grafting density. Langmuir 2004;20:11748–55. [106] Zhao B, Haasch RT, MacLaren S. Solvent-induced self-assembly of mixed poly(methyl methacrylate)/polystyrene brushes on planar silica substrates: molecular weight effect. J Am Chem Soc 2004;126:6124–34. [107] Andruzzi L, Senaratne W, Hexemer A, Sheets ED, Ilic B, Kramer EJ, et al. Oligo(ethylene glycol) containing polymer brushes as bioselective surfaces. Langmuir 2005;21:2495–504. [108] Li J, Chen X, Chang Y-C. Preparation of end-grafted polymer brushes by nitroxide-mediated free radical polymerization of vaporized vinyl monomers. Langmuir 2005;21:9562–7. [109] Xu FJ, Song Y, Cheng ZP, Zhu XL, Zhu CX, Kang ET, et al. Controlled micropatterning of a Si(100) surface by combined nitroxide-mediated and atom transfer radical polymerizations. Macromolecules 2005;38:6254–8. [110] Wang Y, Brittain WJ. Simultaneous binary mixed homopolymer brush formation by combining nitroxide-mediated radical polymerization and living cationic ring-opening polymerization. Macromol Rapid Commun 2007;28:811–5. [111] Lewis GT, Cohen Y. Controlled nitroxide-mediated styrene surface graft polymerization with atmospheric plasma surface activation. Langmuir 2008;24:13102–12. [112] Brinks MK, Studer A. Polymer brushes by nitroxide-mediated polymerization. Macromol Rapid Commun 2009;30:1043–57. [113] Wagner H, Li Y, Hirtz M, Chi L, Fuchs H, Studer A. Site specific protein immobilization into structured polymer brushes prepared by AFM lithography. Soft Matter 2011;7:9854–8. [114] Abraham S, Unsworth LD. Multi-functional initiator and poly(carboxybetaine methacrylamides) for building biocompatible surfaces using ‘‘nitroxide mediated free radical polymerization” strategies. J Polym Sci Part A Polym Chem 2011;49:1051–60. [115] Cimen D, Caykara T. Biofunctional oligo N-isopropylacrylamide brushes on silicon wafer surface. J Mater Chem 2012;22:13231–8. [116] Hentschel C, Wagner H, Smiatek J, Heuer A, Fuchs H, Zhang X, et al. AFM-based force spectroscopy on polystyrene brushes: effect of brush thickness on protein adsorption. Langmuir 2013;29:1850–6. [117] Roling O, Mardyukov A, Krings JA, Studer A, Ravoo BJ. Polymer brushes exhibiting versatile supramolecular interactions grown by nitroxide-mediated polymerization and structured via microcontact chemistry. Macromolecules 2014;47:2411–9. [118] Huber DL, Manginell RP, Samara MA, Kim B-I, Bunker BC. Programmed adsorption and release of protein in a microfluidic device. Science 2003;301:352–4. [119] Alivisatos AP, Gu W, Larabell C. Quantum dots as cellular probes. Annu Rev Biomed Eng 2005;7:55–76. [120] Medintz IL, Uyeda HT, Goldman ER, Mattoussi H. Quantum dot bioconjugates for imaging, labelling and sensing. Nat Mater 2005;4:435–46. [121] Chen H, Zhen Z, Todd T, Chu PK, Xie J. Nanoparticles for improving cancer diagnosis. Mater Sci Eng R 2013;74:35–69. [122] Sill K, Emrick T. Nitroxide-mediated radical polymerization from CdSe nanoparticles. Chem Mater 2004;16:1240–3. [123] Wang HC, Li Y, Yang MJ. Sensors for organic vapor detection based on composites of carbon nanotubes functionalized with polymers. Sens Actuators B 2007;124:360–7. [124] Yang J, Zhang Z, Men X, Xu X, Zhu X. Reversible conversion of water-droplet mobility from rollable to pinned on a superhydrophobic functionalized carbon nanotube film. J Colloid Interface Sci 2010;346:241–7. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 229

[125] Parvole J, Ahrens L, Blas H, Vinas J, Boissiere C, Sanchez C, et al. Grafting polymer chains bearing an n-succinimidyl activated ester end-group onto primary amine-coated silica particles and application of a simple, one-step approach via nitroxide-mediated controlled/living free-radical polymerization. J Polym Sci Part A Polym Chem 2010;48:173–85. [126] Ostaci R-V, Damiron D, Capponi S, Vignaud G, Leger L, Grohens Y, et al. Polymer brushes grafted to passivated silicon substrates using click chemistry. Langmuir 2008;24:2732–9. [127] Homenick CM, Sivasubramaniam U, Adronov A. Effect of polymer chain length on the solubility of polystyrene grafted single-walled carbon nanotubes in tetrahydrofuran. Polym Int 2008;57:1007–11. [128] Halperin A. Polymer brushes that resist adsorption of model proteins: design parameters. Langmuir 1999;15:2525–33. [129] Matyjaszewski K, Xia J. Atom transfer radical polymerization. Chem Rev 2001;101:2921–90. [130] Wang J-S, Matyjaszewski K. Controlled/‘‘living” radical polymerization. Halogen atom transfer radical polymerization promoted by a Cu(I)/Cu(II) redox process. Macromolecules 1995;28:7901–10. [131] Matyjaszewski K, Tsarevsky NV. Nanostructured functional materials prepared by atom transfer radical polymerization. Nat Chem 2009;1:276–88. [132] Wang J-S, Matyjaszewski K. Controlled/‘‘living” radical polymerization. Atom transfer radical polymerization in the presence of transition-metal complexes. J Am Chem Soc 1995;117:5614–5. [133] Ran J, Wu L, Zhang Z, Xu T. Atom transfer radical polymerization (ATRP): a versatile and forceful tool for functional membranes. Prog Polym Sci 2014;39:124–44. [134] Tang W, Kwak Y, Braunecker W, Tsarevsky NV, Coote ML, Matyjaszewski K. Understanding atom transfer radical polymerization: effect of ligand and initiator structures on the equilibrium constants. J Am Chem Soc 2008;130:10702–13. [135] Tang W, Matyjaszewski K. Effect of ligand structure on activation rate constants in ATRP. Macromolecules 2006;39:4953–9. [136] Lena FD, Matyjaszewski K. Transition metal catalysts for controlled radical polymerization. Prog Polym Sci 2010;35:959–1021. [137] Matyjaszewski K, Patten TE, Xia J. Controlled/‘‘living” radical polymerization. kinetics of the homogeneous atom transfer radical polymerizationof styrene. J Am Chem Soc 1997;119:674–80. [138] Patten TE, Matyjaszewski K. Copper(I)-catalyzed atom transfer radical polymerization. Acc Chem Res 1999;32:895–903. [139] Xia J, Matyjaszewski K. Controlled/‘‘living” radical polymerization. Atom transfer radical polymerization catalyzed by copper(I) and picolylamine complexes. Macromolecules 1999;32:2434–7. [140] Xia J, Zhang X, Matyjaszewski K. The effect of ligands on copper-mediated atom transfer radical polymerization. ACS Symp Ser 2000;760:207–23. [141] Sarbu T, Matyjaszewski K. ATRP of methyl methacrylate in the presence of ionic liquids with ferrous and cuprous anions. Macromol Chem Phys 2001;202:3379–91. [142] Hong SC, Matyjaszewski K. Fundamentals of supported catalysts for atom transfer radical polymerization (ATRP) and application of an immobilized/soluble hybrid catalyst system to ATRP. Macromolecules 2002;35:7592–605. [143] Pintauer T, Matyjaszewski K. Atom transfer radical addition and polymerization reactions catalyzed by ppm amounts of copper complexes. Chem Soc Rev 2008;37:1087–97. [144] Gromada J, Spanswick J, Matyjaszewski K. Synthesis and ATRP activity of new TREN-based ligands. Macromol Chem Phys 2004;205:551–66. [145] Gibson VC, O’Reilly RK, Wass DF, White AJP, Williams DJ. Polymerization of methyl methacrylate using four-coordinate (a-diimine)iron catalysts: atom transfer radical polymerization vs catalytic chain transfer. Macromolecules 2003;36:2591–953. [146] Teodorescu M, Gaynor SG, Matyjaszewski K. Halide anions as ligands in iron-mediated atom transfer radical polymerization. Macromolecules 2000;33:2335–9. [147] Xue Z, Linh NTB, Noh SK, Lyoo WS. Phosphorus-containing ligands for iron(III)-catalyzed atom transfer radical polymerization. Angew Chem 2008;120:6526–9. [148] Grognec EL, Claverie J, Poli R. Radical polymerization of styrene controlled by half-sandwich Mo(III)/Mo(IV) couples: all basic mechanisms are possible. J Am Chem Soc 2001;123:9513–24. [149] Maria S, Stoffelbach F, Mata J, Daran J-C, Richard P, Poli R. The radical trap in atom transfer radical polymerization need not be thermodynamically

stable. A Study of the MoX3(PMe3)3 catalysts. J Am Chem Soc 2005;127:5946–56. [150] Braunecker WA, Itami Y, Matyjaszewski K. Osmium-mediated radical polymerization. Macromolecules 2005;38:9402–4. [151] Kato M, Kamigaito M, Sawamoto M, Higashimura T. Polymerization of methyl methacrylate with the carbon tetrachloride/dichlorotris- (triphenylphosphine)ruthenium(II)/methylaluminum bis(2,6-di-tert-butylphenoxide) initiating system: possibility of living radical polymerization. Macromolecules 1995;28:1721–3. [152] Simal F, Demonceau A, Noels AF. Highly efficient ruthenium-based catalytic systems for the controlled free radical polymerization of vinyl monomers. Angew Chem Int Ed 1999;38:538–40. [153] Ando T, Kamigaito M, Sawamoto M. Catalytic activities of ruthenium(II) complexes in transition-metal-mediated living radical polymerization: polymerization, model reaction, and cyclic voltammetry. Macromolecules 2000;33:5825–9. [154] Clercq BD, Verpoort F. A new class of ruthenium complexes containing Schiff base ligands as promising catalysts for atom transfer radical polymerization and ring opening metathesis polymerization. J Mol Catal A Chem 2002;180:67–76. [155] Kamigaito M, Ando T, Sawamoto M. Metal-catalyzed living radical polymerization. Chem Rev 2001;101:3689–745. [156] Feng W, Brash JL, Zhu S. Non-biofouling materials prepared by atom transfer radical polymerization grafting of 2-methacryloloxyethyl phosphorylcholine: separate effects of graft density and chain length on protein repulsion. Biomaterials 2006;27:847–55. [157] Feng W, Zhu S, Ishihara K, Brash JL. Adsorption of fibrinogen and lysozyme on silicon grafted with poly(2-methacryloyloxyethyl phosphorylcholine) via surface-initiated atom transfer radical polymerization. Langmuir 2005;21:5980–7. [158] Xu FJ, Zhong SP, Yung LYL, Kang ET, Neoh KG. Surface-active and stimuli-responsive polymer-Si(100) hybrids from surface-initiated atom transfer radical polymerization for control of cell adhesion. Biomacromolecules 2004;5:2392–403. [159] Ma H, Hyun J, Stiller P, Chilkoti A. ‘‘Non-fouling” oligo(ethylene glycol)-functionalized polymer brushes synthesized by surface-initiated atom transfer radical polymerization. Adv Mater 2004;16:338–41. [160] Singh N, Cui X, Boland T, Husson SM. The role of independently variable grafting density and layer thickness of polymer nanolayers on peptide adsorption and cell adhesion. Biomaterials 2007;28:763–71. [161] Rana D, Matsuura T. Surface modifications for antifouling membranes. Chem Rev 2010;110:2448–71. [162] Tugulu S, Klok H-A. Stability and nonfouling properties of poly(poly(ethylene glycol) methacrylate) brushes under cell culture conditions. Biomacromolecules 2008;9:906–12. [163] Li Y, Neoh KG, Cen L, Kang E-T. Physicochemical and blood compatibility characterization of polypyrrole surface functionalized with heparin. Biotechnol Bioeng 2003;84:305–13. [164] Chen H, Brook MA, Sheardown H. Silicone elastomers for reduced protein adsorption. Biomaterials 2004;25:2273–82. [165] Lan S, Veiseh M, Zhang M. Surface modification of silicon and gold-patterned silicon surfaces for improved biocompatibility and cell patterning selectivity. Biosens Bioelectron 2005;20:1697–708. [166] Ostuni E, Chapman RG, Holmlin RK, Takayama S, Whitesides GM. A survey of structure-property relationships of surfaces that resist the adsorption of protein. Langmuir 2001;17:5605–20. [167] Li L, Chen S, Zheng J, Ratner BD, Jiang S. Protein adsorption on oligo(ethylene glycol)-terminated alkanethiolate self-assembled monolayers: the molecular basis for nonfouling behaviour. J Phys Chem B 2005;109:2934–41. [168] Zheng J, Li L, Tsao H-K, Sheng Y-J, Chen SF, Jiang SY. Strong repulsive forces between protein and oligo (ethylene glycol) self-assembled monolayers: a molecular simulation study. Biophys J 2005;89:158–66. 230 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

[169] Chen S, Zheng J, Li L, Jiang S. Strong resistance of phosphorylcholine self-assembled monolayers to protein adsorption: insights into nonfouling properties of zwitterionic materials. J Am Chem Soc 2005;127:14473–8. [170] Chen S, Yu F, Yu Q, He Y, Jiang S. Strong resistance of a thin crystalline layer of balanced charged groups to protein adsorption. Langmuir 2006;22:8186–91. [171] Yang W, Xue H, Li W, Zhang J, Jiang S. Pursuing, ‘‘zero” protein adsorption of poly(carboxybetaine) from undiluted blood serum and plasma. Langmuir 2009;25:11911–6. [172] Desseaux S, Klok H-A. Temperature-controlled masking/unmasking of cell-adhesive cues with poly(ethylene glycol) methacrylate based brushes. Biomacromolecules 2014;15:3859–65. [173] Zhou Y, Wang S, Ding B, Yang Z. Modification of magnetite nanoparticles via surface-initiated atom transfer radical polymerization (ATRP). Chem Eng J 2008;138:578–85. [174] Hu F, Neoh KG, Cen L, Kang E-T. Cellular response to magnetic nanoparticles ‘‘PEGylated” via surface-initiated atom transfer radical polymerization. Biomacromolecules 2006;7:809–16. [175] Tugulu S, Arnold A, Sielaff I, Johnsson K, Klok H-A. Protein-functionalized polymer brushes. Biomacromolecules 2005;6:1602–7. [176] Fan X, Lin L, Messersmith PB. Cell fouling resistance of polymer brushes grafted from Ti substrates by surface-initiated polymerization: effect of ethylene glycol side chain length. Biomacromolecules 2006;7:2443–8. [177] Fan X, Lin L, Dalsin JL, Messersmith PB. Biomimetic anchor for surface-initiated polymerization from metal substrates. J Am Chem Soc 2005;127:15843–7. [178] Iwata R, Suk-In P, Hoven VP, Takahara A, Akiyoshi K, Iwasaki Y. Control of nanobiointerfaces generated from well-defined biomimetic polymer brushes for protein and cell manipulations. Biomacromolecules 2004;5:2308–14. [179] Sin M-C, Sun Y-M, Chang Y. Zwitterionic-based stainless steel with well-defined polysulfobetaine brushes for general bioadhesive control. ACS Appl Mater Interfaces 2014;6:861–73. [180] Zhang Z, Zhang M, Chen S, Horbett T, Ratner BD, Jiang S. Blood compatibility of surfaces with superlow protein adsorption. Biomaterials 2008;29:4285–91. [181] Cheng G, Zhang Z, Chen S, Bryers JD, Jiang S. Inhibition of bacterial adhesion and biofilm formation on zwitterionic surfaces. Biomaterials 2007;28:4192–9. [182] Chang Y, Chen S, Zhang Z, Jiang S. Highly protein-resistant coatings from well-defined diblock copolymers containing sulfobetaines. Langmuir 2006;22:2222–6. [183] Cheng G, Li G, Xue H, Chen S, Bryers JD, Jiang S. Zwitterionic carboxybetaine polymer surfaces and their resistance to long-term biofilm formation. Biomaterials 2009;30:5234–40. [184] Ladd J, Zhang Z, Chen S, Hower JC, Jiang S. Zwitterionic polymers exhibiting high resistance to nonspecific protein adsorption from human serum and plasma. Biomacromolecules 2008;9:1357–61. [185] Desseaux S, Klok H-A. Fibroblast adhesion on ECM-derived peptide modified poly(2-hydroxyethyl methacrylate) brushes: ligand co-presentation and 3D-localization. Biomaterials 2015;44:24–35. [186] Zhang F, Shi ZL, Chua PH, Kang ET, Neoh KG. Functionalization of titanium surfaces via controlled living radical polymerization: from antibacterial surface to surface for osteoblast adhesion. Ind Eng Chem Res 2007;46:9077–86. [187] Bontempo D, Heredia KL, Fish BA, Maynard HD. Cysteine-reactive polymers synthesized by atom transfer radical polymerization for conjugation to proteins. J Am Chem Soc 2004;126:15372–3. [188] Mei Y, Beers KL, Byrd HCM, VanderHart DL, Washburn NR. Solid-phase ATRP synthesis of peptide-polymer hybrids. J Am Chem Soc 2004;126:3472–6. [189] Mei Y, Wu T, Xu C, Langenbach KJ, Elliott JT, Vogt BD, et al. Tuning cell adhesion on gradient poly(2-hydroxyethyl methacrylate)-grafted surfaces. Langmuir 2005;21:12309–14. [190] Liu Q, Singh A, Lalani R, Liu L. Ultralow fouling polyacrylamide on gold surfaces via surface-Initiated atom transfer radical polymerization. Biomacromolecules 2012;13:1086–92. [191] Cringus-Fundeanu I, Luijten J, van der Mei HC, Busscher HJ, Schouten AJ. Synthesis and characterization of surface-grafted polyacrylamide brushes and their inhibition of microbial adhesion. Langmuir 2007;23:5120–6. [192] Li N, Bai R, Liu C. Enhanced and selective adsorption of mercury ions on chitosan beads grafted with polyacrylamide via surface-initiated atom transfer radical polymerization. Langmuir 2005;21:11780–7. [193] Wu Z, Chen H, Liu X, Zhang Y, Li D, Huang H. Protein adsorption on poly(N-vinylpyrrolidone)-modified silicon surfaces prepared by surface-initiated atom transfer radical polymerization. Langmuir 2009;25:2900–6. [194] Campoccia D, Montanaro L, Arciola CR. The significance of infection related to orthopedic devices and issues of antibiotic resistance. Biomaterials 2006;27:2331–9. [195] Krishnamoorthy M, Hakobyan S, Ramstedt M, Gautrot JE. Surface-initiated polymer brushes in the biomedical field: applications in membrane science, biosensing, cell culture, regenerative medicine and antibacterial coatings. Chem Rev 2014;114:10976–1026. [196] Lee SB, Koepsel RR, Morley SW, Matyjaszewski K, Sun Y, Russell AJ. Permanent, nonleaching antibacterial surfaces. 1. Synthesis by atom transfer radical polymerization. Biomacromolecules 2004;5:877–82. [197] Murata H, Koepsel RR, Matyjaszewski K, Russell AJ. Permanent, non-leaching antibacterial surfaces. 2. How high density cationic surfaces kill bacterial cells. Biomaterials 2007;28:4870–9. [198] Huang J, Murata H, Koepsel RR, Russell AJ, Matyjaszewski K. Antibacterial polypropylene via surface-initiated atom transfer radical polymerization. Biomacromolecules 2007;8:1396–9. [199] Xu FJ, Yuan SJ, Pehkonen SO, Kang ET, Neoh KG. Antimicrobial surfaces of viologen-quaternized poly((2-dimethyl amino)ethyl methacrylate)-Si(100) hybrids from surface-initiated atom transfer radical polymerization. NanoBiotechnology 2006;2:123–34. [200] Yuan SJ, Pehkonen SO, Ting YP, Neoh KG, Kang ET. Inorganic-organic hybrid coatings on stainless steel by layer-by-layer deposition and surface- initiated atom-transfer-radical-polymerization for combating biocorrosion. ACS Appl Mater Interfaces 2009;1:640–52. [201] Qiu J-H, Zhang Y-W, Zhang Y-T, Zhang H-Q, Liu J-D. Synthesis and antibacterial activity of copper-immobilized membrane comprising grafted poly(4- vinylpyridine) chains. J Colloid Interface Sci 2011;354:152–9. [202] Ramstedt M, Cheng N, Azzaroni O, Mossialos D, Mathieu HJ, Huck WTS. Synthesis and characterization of poly(3-sulfopropylmethacrylate) brushes for potential antibacterial applications. Langmuir 2007;23:3314–21. [203] Lenoir S, Pagnoulle C, Galleni M, Compère P, Jérôme R, Detrembleur C. Polyolefin matrixes with permanent antibacterial activity: preparation, antibacterial activity, and action mode of the active species. Biomacromolecules 2006;7:2291–6. [204] Ignatova M, Voccia S, Gilbert B, Markova N, Cossement D, Gouttebaron S, et al. Combination of electrografting and atom-transfer radical polymerization for making the stainless steel surface antibacterial and protein antiadhesive. Langmuir 2006;22:255–62. [205] Thomassin J-M, Lenoir S, Riga J, Jérôme R, Detrembleur C. Grafting of poly[2-(tert-butylamino)ethyl methacrylate] onto polypropylene by reactive blending and antibacterial activity of the copolymer. Biomacromolecules 2007;8:1171–7. [206] Hilpert K, Elliott M, Jenssen H, Kindrachuk J, Fjell CD, Köörner J, et al. Screening and characterization of surface-tethered cationic peptides for antimicrobial activity. Chem Biol 2009;16:58–69. [207] Zhang L, Ning C, Zhou T, Liu X, Yeung KWK, Zhang T, et al. Polymeric nanoarchitectures on Ti-based implants for antibacterial applications. ACS Appl Mater Interfaces 2014;6:17323–45. [208] Gao G, Yu K, Kindrachuk J, Brooks DE, Hancock REW, Kizhakkedathu JN. Antibacterial surfaces based on polymer brushes: investigation on the influence of brush properties on antimicrobial peptide immobilization and antimicrobial activity. Biomacromolecules 2011;12:3715–27. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 231

[209] Gao G, Lange D, Hilpert K, Kindrachuk J, Zou Y, Cheng JTJ, et al. The biocompatibility and biofilm resistance of implant coatings based on hydrophilic polymer brushes conjugated with antimicrobial peptides. Biomaterials 2011;32:3899–909. [210] Godoy-Gallardo M, Mas-Moruno C, Yu K, Manero JM, Gil FJ, Kizhakkedathu JN, et al. Antibacterial properties of hLf1-11 peptide onto titanium surfaces: a comparison study between silanization and surface initiated polymerization. Biomacromolecules 2015;16:483–96. [211] Gil ES, Hudson SM. Stimuli-responsive polymers and their bioconjugates. Prog Polym Sci 2004;29:1173–222. [212] de las Heras Alarcón C, Pennadam S, Alexander C. Stimuli responsive polymers for biomedical applications. Chem Soc Rev 2005;34:276–85. [213] Schmaljohann D. Thermo-and pH-responsive polymers in drug delivery. Adv Drug Delivery Rev 2006;58:1655–70. [214] Roy D, Cambre JN, Sumerlin BS. Future perspectives and recent advances in stimuli-responsive materials. Prog Polym Sci 2010;35:278–301. [215] Mizutani A, Kikuchi A, Yamato M, Kanazawa H, Okano T. Preparation of thermo-responsive polymer brush surfaces and their interaction with cells. Biomaterials 2008;29:2073–81. [216] Xu FJ, Zhong SP, Yung LYL, Tong YW, Kang E-T, Neoh KG. Thermo-responsive comb-shaped copolymer-Si(100) hybrids for accelerated temperature- dependent cell detachment. Biomaterials 2006;27:1236–45. [217] Wei Q, Ji J, Shen J. Synthesis of near-infrared responsive gold nanorod/PNIPAAm core/shell nanohybrids via surface initiated ATRP for smart drug delivery. Macromol Rapid Commun 2008;29:645–50. [218] Zhou Z, Zhu S, Zhang D. Grafting of thermo-responsive polymer inside mesoporous silica with large pore size using ATRP and investigation of its use in drug release. J Mater Chem 2007;17:2428–33. [219] Yamamoto K, Kanazawa H, Matsushima Y, Takai N, Kikuchi A, Okano T. Preparation of packing materials for temperature responsive chromatography. Modification of silica surface with poly(N-isopropylacrylamide). Chromatography 2000;21:209–16. [220] Singh N, Wang J, Ulbricht M, Wickramasinghe SR, Husson SM. Surface-initiated atom transfer radical polymerization: a new method for preparation of polymeric membrane adsorbers. J Membr Sci 2008;309:64–72. [221] Li CY, Wang WC, Xu FJ, Zhang LQ, Yang WT. Preparation of pH-sensitive membranes via dopamine-initiated atom transfer radical polymerization. J Membr Sci 2011;367:7–13. [222] Wu T, Gong P, Szleifer I, Vlc˘ek P, S˘ubr V, Genzer J. Behavior of surface-anchored poly(acrylic acid) brushes with grafting density gradients on solid substrates: 1. Experiment. Macromolecules 2007;40:8756–64. [223] Zhou F, Huck WTS. Surface grafted polymer brushes as ideal building blocks for ‘‘smart” surfaces. Phys Chem Chem Phys 2006;8:3815–23. [224] Li D, He Q, Cui Y, Li J. Fabrication of pH-responsive nanocomposites of gold nanoparticles/poly(4-vinylpyridine). Chem Mater 2007;19:412–7. [225] Zhang M, Liu L, Zhao H, Yang Y, Fu G, He B. Double-responsive polymer brushes on the surface of colloid particles. J Colloid Interface Sci 2006;301:85–91. [226] Schepelina O, Zharov I. Poly(2-(dimethylamino)ethyl methacrylate)-modified nanoporous colloidal films with pH and ion response. Langmuir 2008;24:14188–94. [227] Nordgren N, Rutland MW. Tunable nanolubrication between dual-responsive polyionic grafts. Nano Lett 2009;9:2984–90. [228] Zeng F, Shen Y, Zhu S, Pelton R. Synthesis and characterization of comb-branched polyelectrolytes. 1. preparation of cationic macromonomer of 2- (dimethylamino)ethyl methacrylate by atom transfer radical polymerization. Macromolecules 2000;33:1628–35. [229] Zhang L-X, Cai S-L, Zheng Y-B, Cao X-H, Li Y-Q. Smart homopolymer modification to single glass conical nanopore channels: dual-stimuli-actuated highly efficient ion gating. Adv Funct Mater 2011;21:2103–7. [230] Schepelina O, Poth N, Zharov I. PH-responsive nanoporous silica colloidal membranes. Adv Funct Mater 2010;20:1962–9. [231] Xu F-J, Kang E-T, Neoh K-G. PH- and temperature-responsive hydrogels from crosslinked triblock copolymers prepared via consecutive atom transfer radical polymerizations. Biomaterials 2006;27:2787–97. [232] Yuk SH, Cho SH, Lee SH. PH/temperature-responsive polymer composed of poly((N,N-dimethylamino)ethyl methacrylate-co-ethylacrylamide). Macromolecules 1997;30:6856–9. [233] Lee JH, Lee HB, Andrade JD. Blood compatibility of polyethylene oxide surfaces. Prog Polym Sci 1995;20:1043–79. [234] Xu FJ, Li YL, Kang ET, Neoh KG. Heparin-coupled poly (poly(ethylene glycol) monomethacrylate)-Si(111) hybrids and their blood compatible surfaces. Biomacromolecules 2005;6:1759–68. [235] Sharma S, Johnson RW, Desai TA. Evaluation of the stability of nonfouling ultrathin poly (ethylene glycol) films for silicon-based microdevices. Langmuir 2004;20:348–56. [236] Shen MC, Martinson L, Wagner MS, Castner DG, Ratner BD, Horbett TA. PEO-like plasma polymerized tetraglyme surface interactions with leukocytes and proteins: in vitro and in vivo studies. J Biomater Sci Polym Ed 2002;13:367–90. [237] Ejaz M, Yamamoto S, Ohno K, Tsujii Y, Fukuda T. Controlled graft polymerization of methyl methacrylate on silicon substrate by the combined use of the Langmuir–Blodgett and atom transfer radical polymerization techniques. Macromolecules 1998;31:5934–6. [238] Marutanil E, Yamamoto S, Ninjbadgar T, Tsujii Y, Fukuda T, Takano M. Surface-initiated atom transfer radical polymerization of methyl methacrylate on magnetite nanoparticles. Polymer 2004;45:2231–5. [239] Kong H, Gao C, Yan D. Controlled functionalization of multiwalled carbon nanotubes by in situ atom transfer radical polymerization. J Am Chem Soc 2004;126:412–3. [240] Liu P, Su Z. Surface-initiated atom transfer radical polymerization (SI-ATRP) of styrene from chitosan particles. Mater Lett 2006;60:1137–9. [241] Save M, Granvorka G, Bernard J, Charleux B, Boissière C, Grosso D, et al. Atom transfer radical polymerization of styrene and methyl methacrylate from mesoporous ordered silica particles. Macromol Rapid Commun 2006;27:393–8. [242] Wu H-X, Tong R, Qiu X-Q, Yang H-F, Lin Y-H, Cai R-F, et al. Functionalization of multiwalled carbon nanotubes with polystyrene under atom transfer radical polymerization conditions. Carbon 2007;45:152–9. [243] Sui X, Di Luca A, Gunnewiek MK, Kooij ES, van Blitterswijk CA, Moroni L, et al. Stability and cell adhesion properties of poly(N-isopropylacrylamide) brushes with variable grafting densities. Aust J Chem 2011;64:1261–8. [244] Halperin A, Kröger M. Collapse of thermoresponsive brushes and the tuning of protein adsorption. Macromolecules 2011;44:6986–7005. [245] Meijs GF, Rizzardo E, Thang SH. Preparation of controlled-molecular-weight, olefin-terminated polymers by free radical methods. Chain transfer using allylic sulfides. Macromolecules 1988;21:3122–4. [246] Meijs GF, Rizzardo E. Chain transfer by an addition-fragmentation mechanism. The use of a-benzyloxystyrene for the preparation of low-molecular- weight poly(methyl methacrylate) and polystyrene. Makromol Chem Rapid Commun 1988;9:547–51. [247] Chiefari J, Chong YK, Ercole F, Krstina J, Jeffery J, Le TPT, et al. Living free-radical polymerization by reversible addition-fragmentation chain transfer: the RAFT process. Macromolecules 1998;31:5559–62. [248] Moad G, Rizzardo E, Thang SH. Living radical polymerization by the RAFT process. Aust J Chem 2005;58:379–410. [249] Moad G, Chong YK, Postma A, Rizzardo E, Thang SH. Advances in RAFT polymerization: the synthesis of polymers with defined end-groups. Polymer 2005;46:8458–68. [250] Moad G, Rizzardo E, Thang SH. Radical addition-fragmentation chemistry in polymer synthesis. Polymer 2008;49:1079–131. [251] Stenzel MH, Cummins L, Roberts GE, Davis TP, Vana P, Barner-Kowollik C. Xanthate mediated living polymerization of vinyl acetate: a systematic variation in MADIX/RAFT agent structure. Macromol Chem Phys 2003;204:1160–8. [252] Moad G, Rizzardo E, Thang SH. Living radical polymerization by the RAFT process–a second update. Aust J Chem 2009;62:1402–72. [253] Chiefari J, Mayadunne RTA, Moad CL, Moad G, Rizzardo E, Postma A, et al. Thiocarbonylthio compounds (S@C(Z)SAR) in free radical polymerization with reversible addition-fragmentation chain transfer (RAFT polymerization). Effect of the activating group Z. Macromolecules 2003;36:2273–83. [254] Tsujii Y, Ejaz M, Sato K, Goto A, Fukuda T. Mechanism and kinetics of RAFT-mediated graft polymerization of styrene on a solid surface. 1. Experimental evidence of surface radical migration. Macromolecules 2001;34:8872–8. [255] Beija M, Marty J-D, Destarac M. RAFT/MADIX polymers for the preparation of polymer/inorganic nanohybrids. Prog Polym Sci 2011;36:845–86. 232 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

[256] Hotchkiss JW, Lowe AB, Boyes SG. Surface modification of gold nanorods with polymers synthesized by reversible addition-fragmentation chain transfer polymerization. Chem Mater 2007;19:6–13. [257] Seto H, Takara M, Yamashita C, Murakami T, Hasegawa T, Hoshino Y, et al. Surface modification of siliceous materials using maleimidation and various functional polymers synthesized by reversible addition-fragmentation chain transfer polymerization. ACS Appl Mater Interfaces 2012;4:5125–33. [258] Baum M, Brittain WJ. Synthesis of polymer brushes on silicate substrates via reversible addition fragmentation chain transfer technique. Macromolecules 2002;35:610–5. [259] Huang Y, Liu Q, Zhou X, Perrier S, Zhao Y. Synthesis of silica particles grafted with well-defined living polymeric chains by combination of RAFT polymerization and coupling reaction. Macromolecules 2009;42:5509–17. [260] Ohno K, Ma Y, Huang Y, Mori C, Yahata Y, Tsujii Y, et al. Surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization from fine particles functionalized with trithiocarbonates. Macromolecules 2011;44:8944–53. [261] Roy D, Guthrie JT, Perrier S. Graft polymerization: grafting poly(styrene) from cellulose via reversible addition-fragmentation chain transfer (RAFT) polymerization. Macromolecules 2005;38:10363–72. [262] Rowe-Konopacki MD, Boyes SG. Synthesis of surface initiated diblock copolymer brushes from flat silicon substrates utilizing the RAFT polymerization technique. Macromolecules 2007;40:879–88. [263] Boyer C, Whittaker MR, Nouvel C, Davis TP. Synthesis of hollow polymer nanocapsules exploiting gold nanoparticles as sacrificial templates. Macromolecules 2010;43:1792–9.

[264] Liu J, Zhang L, Shi S, Chen S, Zhou N, Zhang Z, et al. A novel and universal route to SiO2-supported organic/inorganic hybrid noble metal nanomaterials via surface RAFT polymerization. Langmuir 2010;26:14806–13. [265] Bays E, Tao L, Chang C-W, Maynard HD. Synthesis of semitelechelic maleimide poly(PEGA) for protein conjugation by RAFT polymerization. Biomacromolecules 2009;10:1777–81. [266] Chang C-W, Bays E, Tao L, Alconcel SNS, Maynard HD. Differences in cytotoxicity of poly(PEGA)s synthesized by reversible addition-fragmentation chain transfer polymerization. Chem Commun 2009;24:3580–2. [267] Boyer C, Bulmus V, Liu J, Davis TP, Stenzel MH, Barner-Kowollik C. Well-defined protein-polymer conjugates via in situ RAFT polymerization. J Am Chem Soc 2007;129:7145–54. [268] Li M, Li H, De P, Sumerlin BS. Thermoresponsive block copolymer-protein conjugates prepared by grafting-from via RAFT polymerization. Macromol Rapid Commun 2011;32:354–9. [269] Ma M, Zheng S, Chen H, Yao M, Zhang K, Jia X, et al. A combined ‘‘RAFT” and ‘‘graft from” polymerization strategy for surface modification of mesoporous silica nanoparticles: towards enhanced tumor accumulation and cancer therapy efficacy. J Mater Chem B 2014;2:5828–36. [270] Tang J, Hua D, Cheng J, Jiang J, Zhu X. Synthesis and properties of temperature-responsive chitosan by controlled free radical polymerization with chitosan-RAFT agent. Int J Biol Macromol 2008;43:383–9. [271] Zammarelli N, Luksin M, Raschke H, Hergenröder R, Weberskirch R. ‘‘Grafting-from” polymerization of PMMA from stainless steel surfaces by a RAFT- mediated polymerization process. Langmuir 2013;29:12834–43. [272] Tria MCR, Grande CDT, Ponnapati RR, Advincula RC. Electrochemical deposition and surface-initiated RAFT polymerization: protein and cell-resistant PPEGMEMA polymer brushes. Biomacromolecules 2010;11:3422–31. [273] Hinton TM, Guerrero-Sanchez C, Graham JE, Le T, Muir BW, Shi S, et al. The effect of RAFT-derived cationic block copolymer structure on gene silencing efficiency. Biomaterials 2012;33:7631–42. [274] Roy D, Knapp JS, Guthrie JT, Perrier S. Antibacterial cellulose fiber via RAFT surface graft polymerization. Biomacromolecules 2008;9:91–9. [275] Hofs B, de Keizer A, van der Burgh S, Leermakers FAM, Cohen Stuart MA, Millard PE, et al. Complex coacervate core microemulsions. Soft Matter 2008;4:1473–82. [276] Zhu C, Jung S, Si G, Cheng R, Meng F, Zhu X, et al. Cationic methacrylate copolymers containing primary and tertiary amino side groups: controlled synthesis via RAFT polymerization, DNA condensation, and in vitro gene transfection. J Polym Sci Part A Polym Chem 2010;48:2869–77. [277] Li Y, Benicewicz BC. Functionalization of silica nanoparticles via the combination of surface-initiated RAFT polymerization and click reactions. Macromolecules 2008;41:7986–92. [278] Zamfir M, Rodriguez-Emmenegger C, Bauer S, Barner L, Rosenhahn A, Barner-Kowollik C. Controlled growth of protein resistant PHEMA brushes via S- RAFT polymerization. J Mater Chem B 2013;1:6027–34. [279] Zhuang Y, Zhu Q, Tu C, Wang D, Wu J, Xia Y, et al. Protein resistant properties of polymers with different branched architecture on a gold surface. J Mater Chem 2012;22:23852–60. [280] Li L, Kang E, Neoh K. Preparation of well-defined polymer-silicon wafer hybrids via surface-initiated RAFT-mediated process. Appl Surf Sci 2008;254:2600–4. [281] Ahmed M, Narain R. The effect of polymer architecture, composition, and molecular weight on the properties of glycopolymer-based non-viral gene delivery systems. Biomaterial 2011;32:5279–90. [282] Ahmed M, Jawanda M, Ishihara K, Narain R. Impact of the nature, size and chain topologies of carbohydrate-phosphorylcholine polymeric gene delivery systems. Biomaterials 2012;33:7858–70. [283] Fresnais J, Berret J-F, Frka-Petesic B, Sandre O, Perzynski R. Electrostatic co-assembly of iron oxide nanoparticles and polymers: towards the generation of highly persistent superparamagnetic nanorods. Adv Mater 2008;20:3877–81. [284] Kirkland-York S, Zhang Y, Smith AE, York AW, Huang F, McCormick CL. Tailored design of Au nanoparticle-siRNA carriers utilizing reversible addition- fragmentation chain transfer polymers. Biomacromolecules 2010;11:1052–9. [285] Paslay LC, Abel BA, Brown TD, Koul V, Choudhary V, McCormick CL, et al. Antimicrobial poly(methacrylamide) derivatives prepared via aqueous RAFT polymerization exhibit biocidal efficiency dependent upon cation structure. Biomacromolecules 2012;13:2472–82. [286] Venkataraman S, Zhang Y, Liu L, Yang Y-Y. Design, syntheses and evaluation of hemocompatible pegylated-antimicrobial polymers with well- controlled molecular structures. Biomaterials 2010;31:1751–6. [287] Kuroda K, DeGrado WF. Amphiphilic polymethacrylate derivatives as antimicrobial agents. J Am Chem Soc 2005;127:4128–9. [288] Palermo EF, Kuroda K. Chemical structure of cationic groups in amphiphilic polymethacrylates modulates the antimicrobial and hemolytic activities. Biomacromolecules 2009;10:1416–28. [289] Goddard JM, Hotchkiss JH. Polymer surface modification for the attachment of bioactive compounds. Prog Polym Sci 2007;32:698–725. [290] Chu PK, Chen JY, Wang LP, Huang N. Plasma-surface modification of biomaterials. Mater Sci Eng R 2002;36:143–206. [291] Siow KS, Britcher L, Kumar S, Griesser HJ. Plasma methods for the generation of chemically reactive surfaces for biomolecule immobilization and cell colonization – a review. Plasma Process Polym 2006;3:392–418. [292] Baumann L, Hegemann D, de Courten D, Wolf M, Rossi RM, Meier WP, et al. Tuning the resistance of polycarbonate membranes by plasma-induced graft surface modification. Appl Surf Sci 2013;268:450–7. [293] Drummond C, In M, Richetti P. Behavior of adhesive boundary lubricated surfaces under shear: effect of grafted diblock copolymers. Eur Phys J E 2004;15:159–65. [294] Gupta B, Plummer C, Bisson I, Frey P, Hilborn J. Plasma-induced graft polymerization of acrylic acid onto poly(ethylene terephthalate) films: characterization and human smooth muscle cell growth on grafted films. Biomaterials 2002;23:863–71. [295] Wavhal DS, Fisher ER. Hydrophilic modification of polyethersulfone membranes by low temperature plasma-induced graft polymerization. J Membr Sci 2002;209:255–69. [296] Favia P, d’Agostino R. Plasma treatments and plasma deposition of polymers for biomedical applications. Surf Coat Technol 1998;98:1102–6. [297] Oehr C. Plasma surface modification of polymers for biomedical use. Nucl Instrum Methods Phys Res Sect B 2003;208:40–7. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 233

[298] Choi H-S, Kim Y-S, Zhang Y, Tang S, Myung S-W, Shin B-C. Plasma-induced graft co-polymerization of acrylic acid onto the polyurethane surface. Surf Coat Technol 2004;182:55–64. [299] Lu W-L, Huang C-Y, Roan M-L. Effect of plasma treatment on the degree of AAm grafting for high density polyethylene. Surf Coat Technol 2003;172:251–61. [300] Huang C-Y, Lu W-L, Feng Y-C. Effect of plasma treatment on the AAc grafting percentage of high-density polyethylene. Surf Coat Technol 2003;167:1–10. [301] Kai T, Suma Y, Ono S, Yamaguchi T, Nakao S-I. Effect of the pore surface modification of an inorganic substrate on the plasma-grafting behavior of pore-filling-type organic/inorganic composite membranes. J Polym Sci Part A Polym Chem 2006;44:846–56. [302] Gu M, Kilduff JE, Belfort G. High throughput atmospheric pressure plasma-induced graft polymerization for identifying protein-resistant surfaces. Biomaterials 2012;33:1261–70. [303] Chang Y, Chang W-J, Shih Y-J, Wei T-C, Hsiue G-H. Zwitterionic sulfobetaine-grafted poly(vinylidene fluoride) membrane with highly effective blood compatibility via atmospheric plasma-induced surface copolymerization. ACS Appl Mater Interfaces 2011;3:1228–37. [304] Lewis GT, Nowling GR, Hicks RF, Cohen Y. Inorganic surface nanostructuring by atmospheric pressure plasma-induced graft polymerization. Langmuir 2007;23:10756–64. [305] Gu M, Vegas AJ, Anderson DG, Langer RS, Kilduff JE, Belfort G. Combinatorial synthesis with high throughput discovery of protein-resistant membrane surfaces. Biomaterials 2013;34:6133–8. [306] Zhang F, Kang ET, Neoh KG, Wang P, Tan KL. Surface modification of stainless steel by grafting of poly(ethylene glycol) for reduction in protein adsorption. Biomaterials 2001;22:1541–8. [307] Rebl H, Finke B, Lange R, Weltmann K-D, Nebe JB. Impact of plasma chemistry versus titanium surface topography on osteoblast orientation. Acta Biomater 2012;8:3840–51. [308] Vasilev K, Poh Z, Kant K, Chan J, Michelmore A, Losic D. Tailoring the surface functionalities of titania nanotube arrays. Biomaterials 2010;31:532–40. [309] Seo HS, Ko YM, Shim JW, Lim YK, Kook J-K, Cho D-L, et al. Characterization of bioactive RGD peptide immobilized onto poly(acrylic acid) thin films by plasma polymerization. Appl Surf Sci 2010;257:596–602. [310] Kuhn S, Kroth J, Ritz U, Hofmann A, Brendel C, Müller LP, et al. Reduced fibroblast adhesion and proliferation on plasma-modified titanium surfaces. J Mater Sci Mater Med 2014;25:2549–60. [311] Zhong S, Meng Y, Ou Q, Shu X. Plasma induced grafting of PSt onto titanium dioxide powder. II. J Appl Polym Sci 2005;97:2112–7. [312] Ye SH, Johnson CA, Woolley JR, Oh H-I, Gamble LJ, Ishihara K, et al. Surface modification of a titanium alloy with a phospholipid polymer prepared by a plasma-induced grafting technique to improve surface thromboresistance. Colloids Surf B 2009;74:96–102. [313] Magno MHR, Kim J, Srinivasan A, McBride S, Bolikal D, Darr A, et al. Synthesis, degradation and biocompatibility of tyrosine-derived polycarbonate scaffolds. J Mater Chem 2010;20:8885–93. [314] Kim YJ, Kang I-K, Huh MW, Yoon S-C. Surface characterization and in vitro blood compatibility of poly(ethylene terephthalate) immobilized with insulin and/or heparin using plasma glow discharge. Biomaterials 2000;21:121–30. [315] Ma Z, Kotaki M, Yong T, He W, Ramakrishna S. Surface engineering of electrospun polyethylene terephthalate (PET) nanofibers towards development of a new material for blood vessel engineering. Biomaterials 2005;26:2527–36. [316] Kang ET, Zhang Y. Surface modification of fluoropolymers via molecular design. Adv Mater 2000;12:1481–94. [317] Wang C, Chen J-R. Studies on surface graft polymerization of acrylic acid onto PTFE film by remote argon plasma initiation. Appl Surf Sci 2007;253:4599–606. [318] Hsu S-H, Chen W-C. Improved cell adhesion by plasma-induced grafting of L-lactide onto polyurethane surface. Biomaterials 2000;21:359–67. [319] Ding Z, Chen J, Gao S, Chang J, Zhang J, Kang ET. Immobilization of chitosan onto poly-L-lactic acid film surface by plasma graft polymerization to control the morphology of fibroblast and liver cells. Biomaterials 2004;25:1059–67. [320] Yang F, Murugan R, Ramakrishna S, Wang X, Ma Y-X, Wang S. Fabrication of nano-structured porous PLLA scaffold intended for nerve tissue engineering. Biomaterials 2004;25:1891–900. [321] Yang F, Murugan R, Wang S, Ramakrishna S. Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials 2005;26:2603–10. [322] Bettahalli NMS, Steg H, Wessling M, Stamatialis D. Development of poly(L-lactic acid) hollow fiber membranes for artificial vasculature in tissue engineering scaffolds. J Membr Sci 2011;371:117–26.

[323] Chen Y, Gao Q, Wan H, Yi J, Wei Y, Liu P. Surface modification and biocompatible improvement of polystyrene film by Ar, O2 and Ar + O2 plasma. Appl Surf Sci 2013;265:452–7. [324] North SH, Lock EH, Cooper CJ, Franek JB, Taitt CR, Walton SG. Plasma-based surface modification of polystyrene microtiter plates for covalent immobilization of biomolecules. ACS Appl Mater Interfaces 2010;2:2884–91. [325] Chen J-P, Kuo C-Y, Lee W-L. Thermo-responsive wound dressings by grafting chitosan and poly(N-isopropylacrylamide) to plasma-induced graft polymerization modified non-woven fabrics. Appl Surf Sci 2012;262:95–101. [326] Kurosawa S, Aizawa H, Talib ZA, Atthoff B, Hilborn J. Synthesis of tethered-polymer brush by atom transfer radical polymerization from a plasma- polymerized-film-coated quartz crystal microbalance and its application for immunosensors. Biosens Bioelectron 2004;20:1165–76. [327] Ferraz CC, Varca GHC, Ruiz J-C, Lopes PS, Mathor MB, Lugão AB, et al. Radiation-grafting of thermo-and pH-responsive poly(N-vinylcaprolactam-co- acrylic acid) onto silicone rubber and polypropylene films for biomedical purposes. Radiat Phys Chem 2014;97:298–303. [328] Mazzei R, Tadey D, Smolko E, Rocco C. Radiation grafting of different monomers onto PP foils irradiated with 25 MeV proton beam. Nucl Instrum Methods Phys Res Sect B 2003;208:411–5. [329] Kitamura A, Hamamoto S, Taniike A, Ohtani Y, Kubota N, Furuyama Y. Application of proton beams to radiation induced graft polymerization for making amidoxime-type adsorbents. Radiat Phys Chem 2004;69:171–8. [330] Kato K, Uchida E, Kang E-T, Uyama Y, Ikada Y. Polymer surface with graft chains. Prog Polym Sci 2003;28:209–59. [331] Dargaville TR, George GA, Hill DJT, Whittaker AK. High energy radiation grafting of fluoropolymers. Prog Polym Sci 2003;28:1355–76. [332] Gubler L, Gürsel SA, Scherer GG. Radiation grafted membranes for polymer electrolyte fuel cell. Fuel Cells 2005;5:317–35. [333] Wojnárovits L, Földváry CM, Takács E. Radiation-induced grafting of cellulose for adsorption of hazardous water pollutants: a review. Radiat Phys Chem 2010;79:848–62. [334] Aydinli B, Tincer T. Radiation grafting of various water-soluble monomers on ultra-high molecular weight polyethylene powder: Part I. Grafting conditions and grafting yield. Radiat Phys Chem 2001;60:237–43. [335] Nasef MM, Hegazy ESA. Preparation and applications of ion exchange membranes by radiation-induced graft copolymerization of polar monomers onto non-polar films. Prog Polym Sci 2004;29:499–561. [336] Septiani U, Chen J, Asano M, Maekawa Y, Yoshida M, Kubota H. Influence of pre-irradiation atmosphere on the properties of polymer electrolyte membranes prepared using radiation grafting method. J Mater Sci 2007;42:1330–5. [337] Bhattacharya A. Radiation and industrial polymers. Prog Polym Sci 2000;25:371–401. [338] Benson RS. Use of radiation in biomaterials science. Nucl Instrum Methods Phys Res Sect B 2002;191:752–7. [339] Clough RL. High-energy radiation and polymers: a review of commercial processes and emerging applications. Nucl Instrum Methods Phys Res Sect B 2001;185:8–33. [340] Casimiro MH, Botelho ML, Leal JP, Gil MH. Study on chemical, UV and gamma radiation-induced grafting of 2-hydroxyethyl methacrylate onto chitosan. Radiat Phys Chem 2005;72:731–5. [341] Jin W, Yang L, Yang W, Chen B, Chen J. Grafting of HEMA onto dopamine coated stainless steel by 60Co-c irradiation method. Radiat Phys Chem 2014;105:57–62. 234 T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235

[342] Segura T, Burillo G. Radiation modification of silicone rubber with glycidylmethacrylate. Radiat Phys Chem 2013;91:101–7. [343] Enomoto I, Katsumura Y, Kudo H, Sekiguchi M. The role of hydroperoxides as a precursor in the radiation-induced graft polymerization of methyl methacrylate to ultra-high molecular weight polyethylene. Radiat Phys Chem 2010;79:718–24. [344] Magaña H, Palomino K, Cornejo-Bravo JM, Alvarez-Lorenzo C, Concheiro A, Bucio E. Radiation-grafting of acrylamide onto silicone rubber films for diclofenac delivery. Radiat Phys Chem 2015;107:164–70. [345] Singh B, Bala R. Development of hydrogels by radiation induced polymerization for use in slow drug delivery. Radiat Phys Chem 2014;103:178–87. [346] Thakur VK, Tan EJ, Lin M-F, Lee PS. Poly(vinylidene fluoride)-graft-poly(2-hydroxyethyl methacrylate): a novel material for high energy density capacitors. J Mater Chem 2011;21:3751–9. [347] Dumas L, Fleury E, Portinha D. Wettability adjustment of PVDF surfaces by combining radiation-induced grafting of (2,3,4,5,6)-pentafluorostyrene and subsequent chemoselective ‘‘click-type” reaction. Polymer 2014;55:2628–34. [348] Nasef MM, Ali AA, Saidi H, Ahmad A. Modeling and optimization aspects of radiation induced grafting of 4-vinylpyridene onto partially fluorinated films. Radiat Phys Chem 2014;94:123–8. [349] Goel NK, Rao MS, Kumar V, Bhardwaj YK, Chaudhari CV, Dubey KA, et al. Synthesis of antibacterial cotton fabric by radiation-induced grafting of [2- (methacryloyloxy)ethyl]trimethylammonium chloride (MAETC) onto cotton. Radiat Phys Chem 2009;78:399–406. [350] Goel NK, Kumar V, Rao MS, Bhardwaj YK, Sabharwal S. Functionalization of cotton fabrics by radiation induced grafting of quaternary salt to impart antibacterial property. Radiat Phys Chem 2011;80:1233–41. [351] Li R, Wang H, Wang W, Ye Y. Simultaneous radiation induced graft polymerization of N-vinyl-2-pyrrolidone onto polypropylene non-woven fabric for improvement of blood compatibility. Radiat Phys Chem 2013;88:65–9. [352] Kumari M, Gupta B, Ikram S. Characterization of N-isopropyl acrylamide/acrylic acid grafted polypropylene nonwoven fabric developed by radiation- induced graft polymerization. Radiat Phys Chem 2012;81:1729–35. [353] Wang C, Yang F, Zhang H. Fabrication of non-woven composite membrane by chitosan coating for resisting the adsorption of proteins and the adhesion of bacteria. Sep Purif Technol 2010;75:358–65. [354] Zhao J, Shi Q, Luan S, Song L, Yang H, Shi H, et al. Improved biocompatibility and antifouling property of polypropylene non-woven fabric membrane by surface grafting zwitterionic polymer. J Membr Sci 2011;369:5–12. [355] Zhang K, Wu XY. Temperature and pH-responsive polymeric composite membranes for controlled delivery of proteins and peptides. Biomaterials 2004;25:5281–91. [356] He C, Kim SW, Lee DS. In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery. J Controlled Release 2008;127:189–207. [357] Fu H, Gao H, Wu G, Wang Y, Fan Y, Ma J. Preparation and tunable temperature sensitivity of biodegradable polyurethane nanoassemblies from diisocyanate and poly(ethylene glycol). Soft Matter 2011;7:3546–52. [358] Wang A, Gao H, Sun Y, Sun Y-L, Yang Y-W, Wu G, et al. Temperature- and pH-responsive nanoparticles of biocompatible polyurethanes for doxorubicin delivery. Int J Pharm 2013;441:30–9. [359] Barsbay M, Güven O, Stenzel MH, Davis TP, Barner-Kowollik C, Berner L. Verification of controlled grafting of styrene from cellulose via radiation- induced RAFT polymerization. Macromolecules 2007;40:7140–7. [360] Holmberg S, Holmlund P, Nicolas R, Wilén C-E, Kallio T, Sundholm G, et al. Versatile synthetic route to tailor-made proton exchange membranes for fuel cell applications by combination of radiation chemistry of polymers with nitroxide-mediated living free radical graft polymerization. Macromolecules 2004;37:9909–15. [361] Zhai M, Chen J, Hasegawa S, Maekawa Y. Synthesis of fluorinated polymer electrolyte membranes by radiation grafting and atom transfer radical polymerization techniques. Polymer 2009;50:1159–65. [362] Oster G, Shibata O. Graft copolymer of polyacrylamide and natural rubber produced by means of ultraviolet light. J Polym Sci 1957;26:233–4. [363] Wang Y, Bai Y, Zhong W, Huang W, Yang W. Direct construction of discrete large spherical functional particles onto organic material surfaces by photografting polymerization. Macromolecules 2007;40:756–9. [364] Ma H, Davis RH, Bowman CN. A novel sequential photoinduced living graft polymerization. Macromolecules 2000;33:331–5. [365] Ranby B, Yang WT, Tretinnikov O. Surface photografting of polymer fibers, films and sheets. Nucl Instrum Methods Phys Res Sect B 1999;151:301–5. [366] Deng J, Wang L, Liu Li, Yang W. Developments and new applications of UV-induced surface graft polymerizations. Prog Polym Sci 2009;34:156–93. [367] He D, Susanto H, Ulbricht M. Photo-irradiation for preparation, modification and stimulation of polymeric membranes. Prog Polym Sci 2009;34:62–98. [368] He D, Ulbricht M. Surface-selective photo-grafting on porous polymer membranes via a synergist immobilization method. J Mater Chem 2006;16:1860–8. [369] Janorkar AV, Metters AT, Hirt DE. Modification of poly(lactic acid) films: enhanced wettability from surface-confined photografting and increased degradation rate due to an artifact of the photografting process. Macromolecules 2004;37:9151–9. [370] Andrzejewska E. Photopolymerization kinetics of multifunctional monomers. Prog Polym Sci 2001;26:605–65. [371] Luan S, Zhao J, Yang H, Shi H, Jin J, Li X, et al. Surface modification of poly(styrene-b-(ethylene-co-butylene)-b-styrene) elastomer via UV-induced graft polymerization of N-vinyl pyrrolidone. Colloids Surf B 2012;93:127–34. [372] Deng J-P, Yang W-T, Rånby B. Auto-initiating performance of styrene on surface photografting polymerization. Macromol Rapid Commun 2001;22:535–8. [373] Kyomoto M, Moro T, Takatori Y, Kawaguchi H, Nakamura K, Ishihara K. Self-initiated surface grafting with poly (2-methacryloyloxyethyl phosphorylcholine) on poly(ether-ether-ketone). Biomaterials 2010;31:1017–24. [374] Yang Q, Xu Z-K, Dai Z-W, Wang J-L, Ulbricht M. Surface modification of polypropylene microporous membranes with a novel glycopolymer. Chem Mater 2005;17:3050–8. [375] Xing C-M, Deng J-P, Yang W-T. Synthesis of antibacterial polypropylene film with surface immobilized polyvinylpyrrolidone-iodine complex. J Appl Polym Sci 2005;97:2026–31. [376] Yang Q, Hu M-X, Dai Z-W, Tian J, Xu Z-K. Fabrication of glycosylated surface on polymer membrane by UV-induced graft polymerization for lectin recognition. Langmuir 2006;22:9345–9. [377] Yusof AHM, Ulbricht M. Polypropylene-based membrane adsorbers via photo-initiated graft copolymerization: optimizing separation performance by preparation conditions. J Membr Sci 2008;311:294–305. [378] Schneider MH, Tran Y, Tabeling P. Benzophenone absorption and diffusion in poly(dimethylsiloxane) and its role in graft photo-polymerization for surface modification. Langmuir 2011;27:1232–40. [379] Sugiura S, Edahiro J, Sumaru K, Kanamori T. Surface modification of polydimethylsiloxane with photo-grafted poly(ethylene glycol) for micropatterned protein adsorption and cell adhesion. Colloids Surf B 2008;63:301–5. [380] Goda T, Konno T, Takai M, Moro T, Ishihara K. Biomimetic phosphorylcholine polymer grafting from polydimethylsiloxane surface using photo- induced polymerization. Biomaterials 2006;27:5151–60. [381] Mata A, Fleischman AJ, Roy S. Characterization of polydimethylsiloxane (PDMS) properties for biomedical micro/nanosystems. Biomed Microdevices 2005;7:281–93. [382] Deng Y, Xiong D, Wang K. Biotribological properties of UHMWPE grafted with AA under lubrication as artificial joint. J Mater Sci Mater Med 2013;24:2085–91. [383] Kyomoto M, Moro T, Konno T, Takadama H, Kawaguchi H, Takatori Y, et al. Effects of photo-induced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on physical properties of cross-linked polyethylene in artificial hip joints. J Mater Sci Mater Med 2007;18:1809–15. [384] Kyomoto M, Moro T, Miyaji F, Hashimoto M, Kawaguchi H, Takatori Y, et al. Effect of 2-methacryloyloxyethyl phosphorylcholine concentration on photo-induced graft polymerization of polyethylene in reducing the wear of orthopaedic bearing surface. J Biomed Mater Res Part A 2007;86:439–47. T. Zhou et al. / Progress in Materials Science 83 (2016) 191–235 235

[385] Källrot M, Edlund U, Albertsson A-C. Surface functionalization of degradable polymers by covalent grafting. Biomaterials 2006;27:1788–96. [386] Zhu Y, Gao C, Shen J. Surface modification of polycaprolactone with poly(methacrylic acid) and gelatin covalent immobilization for promoting its cytocompatibility. Biomaterials 2002;23:4889–95. [387] Rahimpour A. UV photo-grafting of hydrophilic monomers onto the surface of nano-porous PES membranes for improving surface properties. Desalination 2011;265:93–101. [388] Rahimpour A, Madaeni SS, Zereshki S, Mansourpanah Y. Preparation and characterization of modified nano-porous PVDF membrane with high antifouling property using UV photo-grafting. Appl Surf Sci 2009;255:7455–61. [389] Zhang J, Cui CQ, Lim TB. Chemical Modification of silicon (100) surface via UV-induced graft polymerization. Chem Mater 1999;11:1061–8. [390] Rohr T, Ogletree DF, Svec F, Fréchet JMJ. Surface functionalization of thermoplastic polymers for the fabrication of microfluidic devices by photoinitiated grafting. Adv Funct Mater 2003;13:264–70. [391] Feng J, Haasch RT, Dyer DJ. Photoinitiated synthesis of mixed polymer brushes of polystyrene and poly(methyl methacrylate). Macromolecules 2004;37:9525–37. [392] Stachowiak TB, Svec F, Fréchet JMJ. Patternable protein resistant surfaces for multifunctional microfluidic devices via surface hydrophilization of porous polymer monoliths using photografting. Chem Mater 2006;18:5950–7. [393] Zhu Y, Gao C, Guan J, Shen J. Promoting the cytocompatibility of polyurethane scaffolds via surface photo-grafting polymerization of acrylamide. J Mater Sci Mater Med 2004;15:283–9. [394] Feng Y, Zhao H, Behl M, Lendlein A, Guo J, Yang D. Grafting of poly(ethylene glycol) monoacrylates on polycarbonateurethane by UV initiated polymerization for improving hemocompatibility. J Mater Sci Mater Med 2013;24:61–70. [395] Ishizu K, Kakinuma H. Synthesis of nanocylinders consisting of graft block copolymers by the photo-induced ATRP technique. J Polym Sci Part A Polym Chem 2005;43:63–70. [396] Gromadzki D, Makuška R, Netopilík M, Holler P, Lokaj J, Janata M, et al. Comb copolymers of polystyrene-poly(tert-butyl (meth) acrylate) prepared by combination of nitroxide mediated polymerization and photoinduced iniferter technique. Eur Polym J 2008;44:59–71. [397] Williams DF. Proc of a consensus conf of the Eur soc for biomater, vol. 4. New York: Elsevier; 1986. [398] Chu PK, Wu SL. Biomaterials. In: Abu-Faraj Ziad, editor. Handbook of research on biomedical engineering education and advanced bioenegineering learning: interdisciplinary concepts, vol. 1. IGI-Global; 2012. p. 238 [chapter 6]. [399] Duncan R, Izzo L. Dendrimer biocompatibility and toxicity. Adv Drug Delivery Rev 2005;57:2215–37. [400] Fischer D, Li YX, Ahlemeyer B, Krieglstein J, Kissel T. In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 2003;24:1121–31. [401] Chen HT, Neerman MF, Parrish AR, Simanek EE. Cytotoxicity, hemolysis, and acute in vivo toxicity of dendrimers based on melamine, candidate vehicles for drug delivery. J Am Chem Soc 2004;126:10044–8. [402] Lee JH, Lim Y-B, Choi JS, Lee Y, Kim T-I, Kim HJ, et al. Polyplexes assembled with internally quaternized PAMAM-OH dendrimer and plasmid DNA have a neutral surface and gene delivery potency. Bioconjugate Chem 2003;14:1214–21. [403] Choi JS, Nam K, Park J, Kim JB, Lee JK, Park JS. Enhanced transfection efficiency of PAMAM dendrimer by surface modification with L-arginine. J Controlled Release 2004;99:445–6. [404] Scarioti GD, Lubambo A, Feitosa JPA, Sierakowski MR, Bresolin TMB, de Freitas RA. Nanocapsule of cationic liposomes obtained using ‘‘in situ” acrylic acid polymerization: stability, surface charge and biocompatibility. Colloids Surf B 2011;87:267–72. [405] Morgan DM, Larvin VL, Pearson JL. Biochemical characterization of polycation-induced cytotoxicity to human vascular endothelial cells. J Cell Sci 1989;94:553–9. [406] Malik N, Wiwattanapatapee R, Lorenz K, Frey H, Weener JW, Meijer E, et al. Dendritic polymers: relationship of structure with biological properties. Proc Int Symp Controlled Release Bioact Mater 1997;24:527–8. [407] Fan RR, Zhou LX, Song W, Li DX, Zhang DM, Ye R, et al. Preparation and properties of g-TTCP/PBS nanocomposites and its in vitro biocompatibility assay. Int J Bio Macromol 2013;59:227–34. [408] Dhyani V, Singh N. Controlling the cell adhesion property of silk films by graft polymerization. ACS Appl Mater Interfaces 2014;6:5005–11. [409] Zhou L, Gao C, Xu W, Wang X, Xu Y. Enhanced biocompatibility and biostability of CdTe quantum dots by facile surface-initiated dendritic polymerization. Biomacromolecules 2009;10:1865–74. [410] Haensler J, Szoka FC. Polyamidoamine cascade polymer mediate efficient transfection of cells in culture. Bioconjugate Chem 1993;4:372–9. [411] Fischer D, Bieber T, Li Y, Elsässer H-P, Kissel T. A novel nonviral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity. Pharm Res 1999;19:1273–9. [412] Sugiyama K, Matsumoto T, Yamazaki Y. Evaluation of biocompatibility of the surface of polyethylene films modified with various water soluble polymers using Ar plasma-post polymerization technique. Macromol Mater Eng 2000;282:5–12. [413] Yuan B, Chen Q, Ding W-Q, Liu P-S, Wu S-S, Lin S-C, et al. Copolymer coatings consisting of 2-methacryloyloxyethyl phosphorylcholine and 3- methacryloxypropyl trimethoxysilane via ATRP to improve cellulose biocompatibility. ACS Appl Mater Interfaces 2012;4:4031–9. [414] Song L, Zhao J, Yang H, Jin J, Li XM, Stagnaro P, et al. Biocompatibility of polypropylene non-woven fabric membrane via UV-induced graft polymerization of 2-acrylamido-2 methylpropane sulfonic acid. Appl Surf Sci 2011;258:425–30. [415] Li X, Luan S, Shi H, Yang H, Song L, Jin J, et al. Improved biocompatibility of poly(styrene-b-(ethylene-co-butylene)-b-styrene) elastomer by a surface graft polymerization of hyaluronic acid. Colloids Surf B 2013;102:210–7. [416] Paripovic D, Hall-Bozic H, Klok H-A. Osteoconductive surfaces generated from peptide functionalized poly(2-hydroxyethyl methacrylate-co-2- (methacryloyloxy) ethyl phosphate) brushes. J Mater Chem 2012;22:19570–8. [417] Liu Y, Tan TTY, Yuan SJ, Choong C. Multifunctional P(PEGMA)-REDV conjugated titanium surfaces for improved endothelial cell selectivity and hemocompatibility. J Mater Chem B 2013;1:157–67. [418] Raynor JE, Capadona JR, Collard DM, Petrie TA, García AJ. Polymer brushes and self-assembled monolayers: versatile platforms to control cell adhesion to biomaterials (Review). Biointerphases 2009;4:FA3–FA16. [419] Chollet C, Chanseau C, Remy M, Guignandon A, Bareille R, Labrugère C, et al. The effect of RGD density on osteoblast and endothelial cell behavior on RGD-grafted polyethylene terephthalate surfaces. Biomaterials 2009;30:711–20. [420] Lashkor M, Rawson FJ, Stephenson-Brown A, Preece JA, Mendes PM. Electrically-driven modulation of surface-grafted RGD peptides for manipulation of cell adhesion. Chem Commun 2014;50:15589–92. [421] Choi CKK, Xu YJ, Wang B, Zhu M, Zhang L, Bian L. Substrate coupling strength of integrin-binding ligands modulates adhesion, spreading, and differentiation of human mesenchymal stem cells. Nano Lett 2015;15:6592–600. [422] Yeung CL, Iqbal P, Allan M, Lashkor M, Preece JA. Tuning specific biomolecular interactions using electro-switchable oligopeptide surfaces. Adv Funct Mater 2010;20:2657–63. [423] Yeung CL, Wang X, Lashkor M, Cantini E, Rawson FJ, Lqbal P, et al. Modulation of biointeractions by electrically switchable oligopeptide surfaces: structural requirements and mechanism. Adv Mater Interfaces 2014;1:1300085. [424] Zheng Y, Xiong C, Zhang L. Dose-dependent enhancement of osteoblast cell adhesion, spreading and proliferation on plasma-carboxylated poly (etheretherketone) surface. Mater Lett 2016;164:60–3. [425] Lilge I, Schönherr H. Control of cell attachment and spreading on poly(acrylamide) brushes with varied grafting density. Langmuir 2016;32:838–47. [426] Psarra E, König U, Ueda Y, Bellmann C, Janke A, Bittrich E, et al. Nanostructured biointerfaces: nanoarchitectonics of thermoresponsive polymer brushes impact protein adsorption and cell adhesion. ACS Appl Mater Interfaces 2015;7:12516–29. [427] Hafner D, Ziegler L, Ichwan M, Zhang T, Schneider M, Schiffmann M, et al. Mussel-inspired polymer carpets: direct photografting of polymer brushes on polydopamine nanosheets for controlled cell adhesion. Adv Mater 2016;28:1489–94.