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Chem Soc Rev 1 1 Chem Soc Rev 1 5 TUTORIAL REVIEW 5 Three-dimensional nano-biointerface as a new Q1 Q2 10 platform for guiding cell fate 10 Cite this: DOI: 10.1039/c3cs60419e Xueli Liuab and Shutao Wang*a Three-dimensional nano-biointerface has been emerging as an important topic for chemistry, 15 nanotechnology, and life sciences in recent years. Understanding the exchanges of materials, signals, 15 and energy at biological interfaces has inspired and helped the serial design of three-dimensional nano- biointerfaces. The intimate interactions between cells and nanostructures bring many novel properties, making three-dimensional nano-biointerfaces a powerful platform to guide cell fate in a controllable and accurate way. These advantages and capabilities endow three-dimensional nano-biointerfaces with 20 an indispensable role in developing advanced biological science and technology. This tutorial review is 20 mainly focused on the recent progress of three-dimensional nano-biointerfaces and highlights the new Received 18th November 2013 explorations and unique phenomena of three-dimensional nano-biointerfaces for cell-related DOI: 10.1039/c3cs60419e fundamental studies and biomedical applications. Some basic bio-inspired principles for the design and creation of three-dimensional nano-biointerfaces are also delivered in this review. Current and further 25 www.rsc.org/csr challenges of three-dimensional nano-biointerfaces are finally addressed and proposed. 25 Key learning points (1) Three-dimensional nano-biointerface is an emerging and important direction of cell biointerface design. 30 (2) Three-dimensional nano-biointerfaces are where most exchanges of materials, signals, and energy between cells and their microenvironments take place. 30 (3) Learning from the interior disciplines of biological systems, some basic bio-inspired principles have been applied to design three-dimensional nano- biointerfaces. (4) Three-dimensional nano-biointerfaces provide a novel platform to guide cell fate in a controllable and accurate way, bringing a series of new phenomena and developments of cell-related fundamental biological studies and advanced biomedical applications. 35 35 1. Introduction The design of cell biointerfaces has been predominantly focusing on two aspects, chemical and topographical.1,3±6 In 40 Cells inhabit a complicated microenvironment including extra- recent years, the consideration of mechanical aspect is also 40 cellular matrix (ECM) and neighboring cells. Extensively spa- gradually involved. Along with the development of micro/nano- tiotemporal stimuli in cell microenvironments regulate cell fate fabrication and engineering techniques, it is able to design cell and tissue development. Cells are inherently sensitive to local biointerfaces from simply two-dimensional to complex three- signals from macroscaled to nanoscaled and chemical to dimensional with spatiotemporally chemical/physical fac- 45 physical, such as molecules and structures, soluble and fluidic tors.1,3,5±7 From the chemical aspect, briefly speaking, by 45 factors, and mechanical stimuli.1±3 Cells also communicate molecule-scaled engineering of two-dimensional biointerfaces with the outside through material transfer, molecular recogni- (smooth biointerfaces without surface topography), fundamen- tion, mechanical transduction, and electrical sensing. This tal cell activities have been systematically investigated in the intricate situation raises great challenges and opportunities presence and absence of chemical clues. ECM proteins have 50 to design cell biointerfaces for biomedical applications.4 been patterned to control the size, shape, viability, and differ- 50 entiation of cells, as well as cell±cell contacts.1,7 Chiral mole- cules and groups have also been applied for studying the influence of surface chirality on cell behaviors.8 From the a Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, P. R. China. topographical aspect, on the other hand, micro/nano-patterns 55 E-mail: [email protected]; Fax: +86-10-82627566; Tel: +86-10-82621396 such as grooves, columns, and ridges on biointerfaces exhibit 55 b University of Chinese Academy of Sciences, Beijing 100049, P. R. China different interaction modes with cells compared to smooth This journal is c The Royal Society of Chemistry 2013 Chem. Soc. Rev., 2013, 00, 1 18 | 1 À Tutorial Review Chem Soc Rev 1 biointerfaces.3 Using elastic micropost arrays, the contractile 1 force and the mechanotransduction mechanism of cells can be studied with highly spatial resolution compared to flexible smooth substrates.7 In addition, micro/nano-structures such as 5 nanofibers have been applied for cell culture and scaffolds.4 5 These extensive studies benefit the understanding of funda- mental cell behaviors and cell±material/cell±microenvironment interactions, and promote the development of tissue- engineering materials for advanced biomedical implants and 10 devices. 10 Along with the exploration of cell biointerfaces in the last few decades, the importance of three-dimensional nano- topography has gradually increased, from a supplementary understanding of chemical-aspect cell±material interactions 15 to an essential direction of biological studies and applications. 15 That is because three-dimensional nano-topography is an important part of cell microenvironments, like the nanoscaled villi and podia of cell surfaces and the nanofibers of ECM. Most exchanges of materials, signals, and energy between cells and 20 their microenvironments take place at three-dimensional 20 nanostructured cell interfaces. Learning from the interior dis- Fig. 1 Explorations of three-dimensional (3D) nano-biointerfaces for cell- ciplines of biological systems is an optimal way for biointerface related fundamental biological studies (i.e., enhancing cell adhesion, con- trolling stem-cell differentiation, helping cell interconnection to outside, design and applications. On the other hand, some important and promoting cell sensing to external signals) and advanced biomedical biological directions in recent years, such as stem-cell related applications (i.e., increasing rare-cell detection efficiency, improving anti- 25 regenerative medicine, nerve-cell related neuroprosthetics, and platelet-adhesion capability of blood-contacting device, helping drug 25 rare-cell related cancer diagnosis, have raised higher require- delivery into cells, and realizing effective and long-term cell patterning). ments for precisely nanoscaled control of cell±material inter- actions. These factors all together promote the creation of more advanced and smart biointerfaces at the three-dimensional biointerfaces own a series of unique properties brought by 30 nanoscale. Many novel three-dimensional nano-biointerfaces the intimate interactions between cells and nanostructures. 30 (biointerfaces with three-dimensional nanoscaled topography) These unique properties and capabilities make three- have been developed with the help of advanced nano- dimensional nano-biointerfaces a powerful platform to guide chemistry, nano-fabrication, and nano-engineering methods cell fate in a more controllable and accurate way, such as the and technologies. Different from traditional two-dimensional enhancement of cell adhesion, the control of cell adhesion/ 35 biointerfaces, these novel three-dimensional nano- detachment and stem-cell differentiation, the help of cell 35 Xueli Liu received her BS degree Shutao Wang received his BS 40 in Materials Chemistry from Jilin degree (2000) and MS degree 40 University in 2009. She then took (2003) from Northeast Normal her successive postgraduate and University under the supervision doctoral programs of study in of Prof. Enbo Wang, and his PhD Prof. Lei Jiang's group at the degree in 2007 from ICCAS under 45 Institute of Chemistry Chinese the supervision of Prof. Lei Jiang. 45 Academy of Sciences (ICCAS). Then he worked in the Under the supervision of Prof. Department of Molecular and Lei Jiang and Prof. Shutao Medical Pharmacology and Wang, her current scientific California NanoSystem Institute 50 interest is focused on the design at the University of California at 50 Xueli Liu and fabrication of bio-inspired Shutao Wang Los Angeles, as a postdoctoral surfaces with special wettability researcher (2007±2010). He was and bio-inspired nano-biointerfaces for specific cancer-cell appointed as a full Professor of Chemistry in 2010 at ICCAS. His recognition and isolation. research interests include the design and synthesis of bio-inspired 55 interfacial materials with special adhesion and their applications 55 at the nano-biointerface. 2 | Chem. Soc. Rev., 2013, 00, 1 18 This journal is c The Royal Society of Chemistry 2013 À Chem Soc Rev Tutorial Review 1 interconnection to outside, and the promotion of cell sensing 1 to external mechno-/electrical signals. It has also shown the potential for many important biomedical applications, such as cancer cell detection, blood-contacting device, drug/gene deliv- 5 ery, and cell patterning (Fig. 1). 5 As there have been many high-quality reviews about the design of two-dimensional biointerfaces and micro/nano- patterns for traditional cell-behavior study, cell culture, and tissue engineering,3,5±7 here we specially focus on the new 10 phenomena and developments of three-dimensional nano- 10 biointerfaces in recent years for the controllable and accurate guidance of cell fate. In the following part, the design principles and fabrication methods
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