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A Review on Nanocomposite Hydrogels and Their Biomedical Applications

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A Review on Nanocomposite Hydrogels and Their Biomedical Applications Sci Eng Compos Mater 2019; 154–174 Sci Eng Compos Mater 2018; aop Shirin Rafieian, Hamid Mirzadeh, Hamid Mahdavi* and Mir Esmaeil Masoumi A review on nanocomposite hydrogels and their biomedical applications https://doi.org/10.1515/secm-2017-0161 Hydrogels are interconnected, natural/synthetic poly- Received May 9, 2017; accepted July 22, 2018 mer chains that are connected to each other by crosslink- ers to produce a hydrophilic material with the macro- Abstract: In order to improve the drawbacks related to molecular structure of a gel. They can swell several times hydrogels, nanocomposite hydrogels were developed by their dry weight and may contain up to 99% water or incorporating different types of nanoparticles or nanos- biological fluids [1]. This three-dimensional (3D) highly tructures in the hydrogel network. This review catego- hydrated porous network can mimic the native tissue rizes nanocomposite hydrogels based on the type of their microenvironment and they are typically designed to hold, nanoparticle into four groups of carbon-, polymeric-, release or capture materials [1, 2]. inorganic- and metallic-based nanocomposite hydrogels. There are two types of hydrogels based on the produc- Each type has specific properties that make them appro- tion method: chemical (thermosetting) gels and physical priate for a special purpose. This is mainly attributed to (thermoplastic) gels. Chemical gels are cross-linked cova- the improvement of interactions between nanoparticles lently through different methods, such as polymerization and polymeric chains and to the enhancement of desirable in the presence of a cross-linker or cross-linking of an exist- properties for target applications. The focus of this paper ing polymer with different routes like heating, ultrasound, is on biomedical applications of nanocomposite hydro- UV or γ-irradiation, etc. Physical gels are amorphous net- gels and the most recent approaches made to fulfill their works of hydrophilic polymers held together by noncova- current limitations. lent interactions, such as Van der waals forces, hydrogen bonding, etc. Chemical gels swell but do not dissolve in Keywords: biomedical applications; hydrogels; nanocom- water, whereas physical gels eventually dissolve in water posite hydrogels; nanoparticles; nanostructures. and may be melted by applied heat [3]. In selecting materials for preparing a hydrogel, impor- tant properties should be considered, including swelling, 1 Introduction mechanical properties, diffusion rates and chemical func- tionality. These properties depend on the cross-linking The combination of nanotechnology with other fields of density, the distance between cross-links, the macro- science has attracted increasing attention during the past molecular structures in the gel and on the residual chemi- decades. There have been numerous approaches to incor- cals (monomers, initiators, etc.) [3]. porate nano-scale methods with conventional methods One of the disadvantages of hydrogels is their low toward manufacturing improved materials. Nanocompos- mechanical strength [4], especially when used as tissue ite hydrogels are one example of such a combination engineering scaffolds or in any application that demands between nanotechnology and biomaterial science. high mechanical strength with good tolerance of compres- sion and good elasticity at the same time (e.g. cartilage tissues). Their low mechanical properties make them dif- ficult to handle and load in different parts of the body. *Corresponding author: Hamid Mahdavi, Department of Novel Recent approaches are shifting toward optimizing the Drug Delivery Systems, Iran Polymer and Petrochemical Institute, 15 km Tehran-Karaj Highway, Pajuhesh Science and Technol- mechanical and chemical properties of hydrogels for spe- ogy Park, Pajuhesh Boulevard, Tehran, Iran; and Department of cific biomedical purposes. Biomedical Engineering, Islamic Azad University, Central Tehran The high surface-to-volume and aspect ratios of Branch, PO Box: 112/14975, Tehran, Iran, Fax: +98 21 48662507, nanoparticles and nano-layers has made them a good e-mail: [email protected] choice for use in the network of polymeric materials [5]. Shirin Rafieian and Mir Esmaeil Masoumi: Department of Chemical The physical/chemical crosslinking of polymeric chains Engineering, Islamic Azad University, North Tehran Branch, Tehran, Iran with different nano-scaled structures leads to a network Hamid Mirzadeh: Polymer and Color Engineering Department, with new exclusive properties, which is called a nanocom- Amirkabir University of Technology, Tehran, Iran posite hydrogel [1, 2]. Novel properties and behaviors Open Access. © 2019 Rafieian et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution alone 4.0 License. Unauthenticated Download Date | 3/18/19 3:18 PM Sci Eng Compos Mater 2018; aop 2 | S. Rafieian et al.: Biomedical applications of S.nanocomposite Rafieian et al.: Biomedicalhydrogels applications of nanocomposite hydrogels 155 Shirin Rafieian, Hamid Mirzadeh, Hamid Mahdavi* and Mir Esmaeil Masoumi Nanoparticles Structure Polymers Polymeric Carbon-based Synthetic polymers Processing Poly(ethylene glycol). A review on nanocomposite hydrogels and their Poly(hydroxyethylmethacrylate). Poly(acryl amide). Poly(vinyl alcohol). biomedical applications Poly(N-isopropylacrylamide). Performance Poly(vinylpyrrolidone). Metallic Inorganic Properties https://doi.org/10.1515/secm-2017-0161 Hydrogels are interconnected, natural/synthetic poly- 25–30 nm Natural polymers Received May 9, 2017; accepted July 22, 2018 Gelatin, Alginate, Chitosan, mer chains that are connected to each other by crosslink- Cellulose, Dextran, Fibrin, Starch, ers to produce a hydrophilic material with the macro- 1 nm Hyaluronic acid, Collagen, Silk, Agarose. Abstract: In order to improve the drawbacks related to molecular structure of a gel. They can swell several times 25–30 nm Nanocomposite biomaterials hydrogels, nanocomposite hydrogels were developed by their dry weight and may contain up to 99% water or incorporating different types of nanoparticles or nanos- biological fluids [1]. This three-dimensional (3D) highly Mechanically tough Stimuli responsive tructures in the hydrogel network. This review catego- hydrated porous network can mimic the native tissue Regenerative Drug & gene rizes nanocomposite hydrogels based on the type of their microenvironment and they are typically designed to hold, medicine delivery nanoparticle into four groups of carbon-, polymeric-, release or capture materials [1, 2]. inorganic- and metallic-based nanocomposite hydrogels. There are two types of hydrogels based on the produc- Microfabricated structures Adhesive gels Each type has specific properties that make them appro- tion method: chemical (thermosetting) gels and physical UV Mask priate for a special purpose. This is mainly attributed to (thermoplastic) gels. Chemical gels are cross-linked cova- Biodevices & Pre polymer Contact biosensors solution lens the improvement of interactions between nanoparticles lently through different methods, such as polymerization Skin and polymeric chains and to the enhancement of desirable in the presence of a cross-linker or cross-linking of an exist- properties for target applications. The focus of this paper ing polymer with different routes like heating, ultrasound, Patterned structure is on biomedical applications of nanocomposite hydro- UV or γ-irradiation, etc. Physical gels are amorphous net- Wound dressing Biossays gels and the most recent approaches made to fulfill their works of hydrophilic polymers held together by noncova- current limitations. lent interactions, such as Van der waals forces, hydrogen Figure 1: The nanocomposite hydrogels for biomedical applications. Adapted from Ref. [2], Copyright (2013), with permission from John bonding, etc. Chemical gels swell but do not dissolve in Keywords: biomedical applications; hydrogels; nanocom- Wiley & Sons, Inc. water, whereas physical gels eventually dissolve in water posite hydrogels; nanoparticles; nanostructures. and may be melted by applied heat [3]. are observed after the nanoscale dispersion of fillers in of bridges between the polymer chains. The optimized In selecting materials for preparing a hydrogel, impor- the composite. Such dispersion can also improve some mechanical strength is a vital property for biomateri- tant properties should be considered, including swelling, properties that already exist in the unfilled matrices als used in regenerative medicine, wound dressings and 1 Introduction mechanical properties, diffusion rates and chemical func- [1, 6]. contact lenses. tionality. These properties depend on the cross-linking The combination of nanotechnology with other fields of Nanomaterials with different bases are used to attain – Adhesion to surfaces, especially skin or soft tissues, density, the distance between cross-links, the macro- science has attracted increasing attention during the past nanocomposite hydrogels. Carbon-based nanomateri- which makes hydrogels a potential wound dressing molecular structures in the gel and on the residual chemi- decades. There have been numerous approaches to incor- als (carbon nanotubes or CNTs, graphene, nanodia- material with ease of load/unload and handle on the cals (monomers, initiators, etc.) [3]. porate nano-scale methods with conventional methods monds), polymeric nanoparticles (dendrimers and hyper- body surface. This adhesion is due to the surface One of the disadvantages of
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