The potential of cellulose nanocrystals in tissue engineering strategies.

Cellulose nanocrystals (CNCs) are a renewable nanosized raw material that is drawing a tremendous level of attention from the materials community. These rod-shaped nanocrystals that can be produced from a variety of highly available and renewable cellulose-rich sources are endowed with exceptional physicochemical properties which have promoted their intensive exploration as building blocks for the design of a broad range of new materials in the past few decades. However, only recently have these nanosized substrates been considered for bioapplications following the knowledge on their low toxicity and ecotoxicological risk. This Review provides an overview on the recent developments on CNC-based functional biomaterials with potential for tissue engineering (TE) applications, focusing on nanocomposites obtained through different processing technologies usually employed in the fabrication of TE scaffolds into various formats, namely, dense films and membranes, hierarchical three-dimensional (3D) porous constructs (micro/nanofibers mats, foams and sponges), and hydrogels. Finally, while highlighting the major achievements and potential of the reviewed work on cellulose nanocrystals, alternative applications for some of the developed materials are provided, and topics for future research to extend the use of CNCs-based materials in the scope of the TE field are identified.

[1]  S. Eichhorn,et al.  Elastic modulus and stress-transfer properties of tunicate cellulose whiskers. , 2005, Biomacromolecules.

[2]  J. Blaker,et al.  Ice microsphere templating to produce highly porous nanocomposite PLA matrix scaffolds with pores selectively lined by bacterial cellulose nano-whiskers , 2010 .

[3]  M. Wolcott,et al.  Study of the Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Cellulose Nanowhisker Composites Prepared by Solution Casting and Melt Processing , 2008 .

[4]  S. Eichhorn,et al.  Determination of the stiffness of cellulose nanowhiskers and the fiber-matrix interface in a nanocomposite using Raman spectroscopy , 2008 .

[5]  Julian H. George,et al.  Exploring and Engineering the Cell Surface Interface , 2005, Science.

[6]  P. Chang,et al.  Structure and properties of polysaccharide nanocrystal-doped supramolecular hydrogels based on Cyclodextrin inclusion , 2010 .

[7]  Elliot L Chaikof,et al.  Biomaterials for vascular tissue engineering. , 2010, Regenerative medicine.

[8]  Sudha Agarwal,et al.  Improved cellular infiltration in electrospun fiber via engineered porosity. , 2007, Tissue engineering.

[9]  M. Wolcott,et al.  Preparation and properties of aligned poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/cellulose nanowhiskers composites. , 2013, Carbohydrate polymers.

[10]  Fumiko Kimura,et al.  Magnetic alignment of the chiral nematic phase of a cellulose microfibril suspension. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[11]  F. Cotana,et al.  Production of nanocrystalline cellulose from lignocellulosic biomass: technology and applications. , 2013, Carbohydrate polymers.

[12]  T. V. van Kuppevelt,et al.  Construction of collagen scaffolds that mimic the three-dimensional architecture of specific tissues. , 2007, Tissue engineering.

[13]  S. Eichhorn,et al.  Oriented surfaces of adsorbed cellulose nanowhiskers promote skeletal muscle myogenesis. , 2013, Acta biomaterialia.

[14]  E. Fortunati,et al.  Biodegradable polymer matrix nanocomposites for tissue engineering: A review , 2010 .

[15]  L. Mattoso,et al.  Cytotoxicity and expression of genes involved in the cellular stress response and apoptosis in mammalian fibroblast exposed to cotton cellulose nanofibers , 2013, Nanotechnology.

[16]  P Laippala,et al.  Is cellulose sponge degradable or stable as implantation material? An in vivo subcutaneous study in the rat. , 1999, Biomaterials.

[17]  W. Walsh,et al.  Influence of different polymeric gels on the ectopic bone forming ability of an osteoinductive biphasic calcium phosphate ceramic. , 2011, Acta biomaterialia.

[18]  Jeffrey R Capadona,et al.  Bioinspired water-enhanced mechanical gradient nanocomposite films that mimic the architecture and properties of the squid beak. , 2013, Journal of the American Chemical Society.

[19]  Ashlie Martini,et al.  Cellulose nanomaterials review: structure, properties and nanocomposites. , 2011, Chemical Society reviews.

[20]  Bengt Fadeel,et al.  Toxicology of engineered nanomaterials: focus on biocompatibility, biodistribution and biodegradation. , 2011, Biochimica et biophysica acta.

[21]  D. Bhattacharyya,et al.  The effects of cellulose nanowhiskers on electrospun poly (lactic acid) nanofibres , 2012, Journal of Materials Science.

[22]  Lennart Möller,et al.  Intracellular uptake and toxicity of Ag and CuO nanoparticles: a comparison between nanoparticles and their corresponding metal ions. , 2013, Small.

[23]  Lucian A. Lucia,et al.  CELLULOSIC NANOCOMPOSITES: A REVIEW , 2008 .

[24]  Zhibin He,et al.  Preparation and characterization of thermal/pH-sensitive hydrogel from carboxylated nanocrystalline cellulose , 2012 .

[25]  Makarand V Risbud,et al.  Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. , 2005, Biomaterials.

[26]  John H T Luong,et al.  Applications of functionalized and nanoparticle-modified nanocrystalline cellulose. , 2012, Trends in biotechnology.

[27]  M. Karaaslan,et al.  Nanoreinforced biocompatible hydrogels from wood hemicelluloses and cellulose whiskers , 2011 .

[28]  Benjamin Chu,et al.  Functional electrospun nanofibrous scaffolds for biomedical applications. , 2007, Advanced drug delivery reviews.

[29]  L. Rueda,et al.  In situ polymerization and characterization of elastomeric polyurethane-cellulose nanocrystal nanocomposites. Cell response evaluation , 2013, Cellulose.

[30]  Seeram Ramakrishna,et al.  Design strategies of tissue engineering scaffolds with controlled fiber orientation. , 2007, Tissue engineering.

[31]  Wei Xue,et al.  Preparation and properties of cellulose nanocrystals reinforced collagen composite films. , 2014, Journal of biomedical materials research. Part A.

[32]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[33]  Kristiina Oksman,et al.  Optimization of the isolation of nanocrystals from microcrystalline cellulose by acid hydrolysis , 2006 .

[34]  Dietmar Werner Hutmacher,et al.  State of the art and future directions of scaffold‐based bone engineering from a biomaterials perspective , 2007, Journal of tissue engineering and regenerative medicine.

[35]  S. Kelley,et al.  Ultrathin film coatings of aligned cellulose nanocrystals from a convective-shear assembly system and their surface mechanical properties , 2011 .

[36]  T. Heinze,et al.  Polysaccharide materials : performance by design , 2010 .

[37]  S. Ostrovidov,et al.  Gradient biomaterials for soft-to-hard interface tissue engineering. , 2011, Acta biomaterialia.

[38]  K. Lee,et al.  Electrospun three‐dimensional silk fibroin nanofibrous scaffold , 2007 .

[39]  A. Mikos,et al.  Electrospinning of polymeric nanofibers for tissue engineering applications: a review. , 2006, Tissue engineering.

[40]  Youssef Habibi,et al.  Key advances in the chemical modification of nanocelluloses. , 2014, Chemical Society reviews.

[41]  J. Luong,et al.  Effect of surface charge on the cellular uptake and cytotoxicity of fluorescent labeled cellulose nanocrystals. , 2010, ACS applied materials & interfaces.

[42]  S. Eichhorn Cellulose nanowhiskers: promising materials for advanced applications , 2011 .

[43]  J. Dorgan,et al.  Supra-molecular ecobionanocomposites based on polylactide and cellulosic nanowhiskers: synthesis and properties. , 2012, Biomacromolecules.

[44]  F. Ko,et al.  Effects of emulsion droplet size on the structure of electrospun ultrafine biocomposite fibers with cellulose nanocrystals. , 2013, Biomacromolecules.

[45]  Casey K. Chan,et al.  Degradation of electrospun nanofiber scaffold by short wave length ultraviolet radiation treatment and its potential applications in tissue engineering. , 2008, Tissue engineering. Part A.

[46]  Yulin Deng,et al.  Increased mechanical properties of aligned and isotropic electrospun PVA nanofiber webs by cellulose nanowhisker reinforcement , 2011, Macromolecular Research.

[47]  R Langer,et al.  Laminated three-dimensional biodegradable foams for use in tissue engineering. , 1993, Biomaterials.

[48]  Patrick A.C. Gane,et al.  Analysis of the shortness of offset ink as a function of tack on paper by comparing elastic and Hencky strain extension , 2011 .

[49]  E. Ureña-Benavides,et al.  Effect of jet stretch and particle load on cellulose nanocrystal-alginate nanocomposite fibers. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[50]  D. Kaplan,et al.  Clues for biomimetics from natural composite materials. , 2012, Nanomedicine.

[51]  S. Stoyanov,et al.  Novel anisotropic materials from functionalised colloidal cellulose and cellulose derivatives , 2010 .

[52]  Rangam Rajkhowa,et al.  Silk fibroin biomaterials for tissue regenerations. , 2013, Advanced drug delivery reviews.

[53]  S. Montesano,et al.  PVA bio-nanocomposites: a new take-off using cellulose nanocrystals and PLGA nanoparticles. , 2014, Carbohydrate polymers.

[54]  J. Araki,et al.  Influence of surface charge on viscosity behavior of cellulose microcrystal suspension , 1999, Journal of Wood Science.

[55]  P. Calvert Hydrogels for Soft Machines , 2009 .

[56]  D. Petri,et al.  Cellulose Acetate Propionate Coated Titanium: Characterization and Biotechnological Application , 2007 .

[57]  Ali Khademhosseini,et al.  Fiber-based tissue engineering: Progress, challenges, and opportunities. , 2013, Biotechnology advances.

[58]  Andreas Greiner,et al.  Electrospinning: a fascinating method for the preparation of ultrathin fibers. , 2007, Angewandte Chemie.

[59]  J. Revol On the cross-sectional shape of cellulose crystallites in Valonia ventricosa , 1982 .

[60]  Alain Dufresne,et al.  Preparation, properties and applications of polysaccharide nanocrystals in advanced functional nanomaterials: a review. , 2012, Nanoscale.

[61]  Alain Dufresne,et al.  Polysaccharide nano crystal reinforced nanocomposites , 2008 .

[62]  D. Gray,et al.  Effect of microcrystallite preparation conditions on the formation of colloid crystals of cellulose , 1998 .

[63]  J. Burdick,et al.  Electrospun fibrous scaffolds with multiscale and photopatterned porosity. , 2010, Macromolecular bioscience.

[64]  Tal Dvir,et al.  Nanotechnological strategies for engineering complex tissues. , 2020, Nature nanotechnology.

[65]  H. Jin,et al.  Electrospinning of Poly(ethylene oxide) with Bacterial Cellulose Whiskers , 2007 .

[66]  V. Kagan,et al.  In Vivo Evaluation of the Pulmonary Toxicity of Cellulose Nanocrystals: A Renewable and Sustainable Nanomaterial of the Future. , 2014, ACS sustainable chemistry & engineering.

[67]  S. Hollister Scaffold Design and Manufacturing: From Concept to Clinic , 2009, Advanced materials.

[68]  D. Mooney,et al.  Hydrogels for tissue engineering. , 2001, Chemical Reviews.

[69]  J. Putaux,et al.  The shape and size distribution of crystalline nanoparticles prepared by acid hydrolysis of native cellulose. , 2008, Biomacromolecules.

[70]  A. Ragauskas,et al.  Cellulose nanowhisker foams by freeze casting , 2012 .

[71]  D. Hutmacher,et al.  Scaffolds in tissue engineering bone and cartilage. , 2000, Biomaterials.

[72]  Shunqing Tang,et al.  Agarose/collagen composite scaffold as an anti-adhesive sheet , 2007, Biomedical materials.

[73]  J. Kadla,et al.  Effect of nanofillers on carboxymethyl cellulose/hydroxyethyl cellulose hydrogels , 2009 .

[74]  R. Sun,et al.  Mechanical and viscoelastic properties of cellulose nanocrystals reinforced poly(ethylene glycol) nanocomposite hydrogels. , 2013, ACS applied materials & interfaces.

[75]  Y. Habibi,et al.  AC electric field‐assisted assembly and alignment of cellulose nanocrystals , 2008 .

[76]  Chengjun Zhou,et al.  Electrospun polyethylene oxide/cellulose nanocrystal composite nanofibrous mats with homogeneous and heterogeneous microstructures. , 2011, Biomacromolecules.

[77]  Lina Zhang,et al.  Effects of Freezing/Thawing Cycles and Cellulose Nanowhiskers on Structure and Properties of Biocompatible Starch/PVA Sponges , 2010 .

[78]  Takeshi Okano,et al.  Birefringent Glassy Phase of a Cellulose Microcrystal Suspension , 2000 .

[79]  E. Ureña-Benavides,et al.  Cellulose Nanocrystal Reinforced Alginate Fibers—Biomimicry Meets Polymer Processing , 2012 .

[80]  A. Dufresne Processing of Polymer Nanocomposites Reinforced with Polysaccharide Nanocrystals , 2010, Molecules.

[81]  Dibyendu Das,et al.  Gel-nanocomposites: materials with promising applications , 2012 .

[82]  Wim E Hennink,et al.  Hydrogels for protein delivery. , 2012, Chemical reviews.

[83]  M. Wolcott,et al.  Effects of Cellulose Nanowhiskers on Mechanical, Dielectric, and Rheological Properties of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Cellulose Nanowhisker Composites , 2012 .

[84]  K. Letchford,et al.  The use of nanocrystalline cellulose for the binding and controlled release of drugs , 2011, International journal of nanomedicine.

[85]  S. Eichhorn,et al.  Directing the morphology and differentiation of skeletal muscle cells using oriented cellulose nanowhiskers. , 2010, Biomacromolecules.

[86]  Jia-cong Shen,et al.  A polylactide/fibrin gel composite scaffold for cartilage tissue engineering: fabrication and an in vitro evaluation , 2009, Journal of materials science. Materials in medicine.

[87]  M. Kotb,et al.  Toxicity of novel nanosized formulations used in medicine. , 2013, Methods in molecular biology.

[88]  Ulrike G K Wegst,et al.  Biomaterials by freeze casting , 2010, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[89]  R. Reis,et al.  Methodologies for processing biodegradable and natural origin scaffolds for bone and cartilage tissue-engineering applications. , 2004, Methods in molecular biology.

[90]  Yang Wang,et al.  Medical applications of biopolyesters polyhydroxyalkanoates , 2013, Chinese Journal of Polymer Science.

[91]  C. Lim,et al.  Fabrication of large pores in electrospun nanofibrous scaffolds for cellular infiltration: a review. , 2012, Tissue engineering. Part B, Reviews.

[92]  Qi Zhou,et al.  Functionalized cellulose nanocrystals as biobased nucleation agents in poly(l-lactide) (PLLA) – Crystallization and mechanical property effects , 2010 .

[93]  M. Tsuji,et al.  Phase separation behavior in aqueous suspensions of bacterial cellulose nanocrystals prepared by sulfuric acid treatment. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[94]  N. Durán,et al.  Review of cellulose nanocrystals patents: preparation, composites and general applications. , 2012, Recent patents on nanotechnology.

[95]  M. Frey,et al.  Nanocomposite Fibers Electrospun from Poly(lactic acid)/Cellulose Nanocrystals , 2009 .

[96]  O. Rojas,et al.  Nanofiber composites of polyvinyl alcohol and cellulose nanocrystals: manufacture and characterization. , 2010, Biomacromolecules.

[97]  C. Breuer,et al.  Vascular tissue engineering: the next generation. , 2012, Trends in molecular medicine.

[98]  A. Ragauskas,et al.  Nanoreinforced xylan–cellulose composite foams by freeze-casting , 2012 .

[99]  R. Sun,et al.  Studies on the properties and formation mechanism of flexible nanocomposite hydrogels from cellulose nanocrystals and poly(acrylic acid) , 2012 .

[100]  R. Tannenbaum,et al.  Mechanical behavior of a cellulose-reinforced scaffold in vascular tissue engineering. , 2012, Journal of the mechanical behavior of biomedical materials.

[101]  Makarand V Risbud,et al.  Tissue engineering: advances in in vitro cartilage generation. , 2002, Trends in biotechnology.

[102]  David L Kaplan,et al.  Natural and Genetically Engineered Proteins for Tissue Engineering. , 2012, Progress in polymer science.

[103]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[104]  Wei Zhang,et al.  Uniaxially aligned electrospun all-cellulose nanocomposite nanofibers reinforced with cellulose nanocrystals: scaffold for tissue engineering. , 2014, Biomacromolecules.

[105]  Sheryl E. Philip,et al.  Poly(3-hydroxybutyrate) multifunctional composite scaffolds for tissue engineering applications. , 2010, Biomaterials.

[106]  M. Corcuera,et al.  Isocyanate-rich cellulose nanocrystals and their selective insertion in elastomeric polyurethane , 2011 .

[107]  Dietmar W Hutmacher,et al.  Combining electrospun scaffolds with electrosprayed hydrogels leads to three-dimensional cellularization of hybrid constructs. , 2008, Biomacromolecules.

[108]  P. Janmey,et al.  Tissue Cells Feel and Respond to the Stiffness of Their Substrate , 2005, Science.

[109]  S. Van Vlierberghe,et al.  Biopolymer-based hydrogels as scaffolds for tissue engineering applications: a review. , 2011, Biomacromolecules.

[110]  A. Dufresne,et al.  Thermoplastic Nanocomposites Filled With Wheat Straw Cellulose Whiskers. Part II: Effect of Processing and Modeling , 1997 .

[111]  A. Crosby,et al.  Photo-cross-linked PLA-PEO-PLA hydrogels from self-assembled physical networks: mechanical properties and influence of assumed constitutive relationships. , 2008, Biomacromolecules.

[112]  Yordan Kostov,et al.  Functional cardiac cell constructs on cellulose-based scaffolding. , 2004, Biomaterials.

[113]  Sabu Thomas,et al.  Preparation of Bionanomaterials and their Polymer Nanocomposites from Waste and Biomass , 2010 .

[114]  Siddaramaiah,et al.  Augmented properties of PVA hybrid nanocomposites containing cellulose nanocrystals and silver nanoparticles , 2012 .

[115]  R. Reis,et al.  Unleashing the potential of supercritical fluids for polymer processing in tissue engineering and regenerative medicine , 2013 .

[116]  Lina Zhang,et al.  Effect of microcrystal cellulose and cellulose whisker on biocompatibility of cellulose-based electrospun scaffolds , 2013, Cellulose.

[117]  Masami Okamoto,et al.  Synthetic biopolymer nanocomposites for tissue engineering scaffolds , 2013 .

[118]  Qi Zhou,et al.  Strong Nanocomposite Reinforcement Effects in Polyurethane Elastomer with Low Volume Fraction of Cellulose Nanocrystals , 2011 .

[119]  E. Fortunati,et al.  Effects of modified cellulose nanocrystals on the barrier and migration properties of PLA nano-biocomposites. , 2012, Carbohydrate polymers.

[120]  Andrew I. Cooper,et al.  Aligned two- and three-dimensional structures by directional freezing of polymers and nanoparticles , 2005, Nature materials.

[121]  Chengjun Zhou,et al.  Mechanical properties and in vitro degradation of electrospun bio-nanocomposite mats from PLA and cellulose nanocrystals. , 2012, Carbohydrate polymers.

[122]  P. Dubois,et al.  From interfacial ring-opening polymerization to melt processing of cellulose nanowhisker-filled polylactide-based nanocomposites. , 2011, Biomacromolecules.

[123]  L. Rueda,et al.  Cellulose nanocrystals/polyurethane nanocomposites. Study from the viewpoint of microphase separated structure. , 2013, Carbohydrate polymers.

[124]  A. Dufresne,et al.  Supramolecular hydrogels from in situ host-guest inclusion between chemically modified cellulose nanocrystals and cyclodextrin. , 2013, Biomacromolecules.

[125]  Se Youn Cho,et al.  Bacterial cellulose nanocrystals-embedded silk nanofibers. , 2012, Journal of nanoscience and nanotechnology.

[126]  Zhe Zhou,et al.  Simultaneous improvement of mechanical properties and thermal stability of bacterial polyester by cellulose nanocrystals. , 2012, Carbohydrate polymers.

[127]  H. S. Azevedo,et al.  Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends , 2007, Journal of The Royal Society Interface.

[128]  Christoph Weder,et al.  Polymer nanocomposites with nanowhiskers isolated from microcrystalline cellulose. , 2009, Biomacromolecules.

[129]  L. Lucia,et al.  Cellulose nanocrystals: chemistry, self-assembly, and applications. , 2010, Chemical reviews.

[130]  Zhiyong Tang,et al.  Biomedical Applications of Layer‐by‐Layer Assembly: From Biomimetics to Tissue Engineering , 2006 .

[131]  S. Eichhorn,et al.  Influence of magnetic field alignment of cellulose whiskers on the mechanics of all-cellulose nanocomposites. , 2012, Biomacromolecules.

[132]  Seung Won Shin,et al.  Size- and dose-dependent toxicity of cellulose nanocrystals (CNC) on human fibroblasts and colon adenocarcinoma. , 2014, Colloids and surfaces. B, Biointerfaces.

[133]  D. Kaplan,et al.  Porosity of 3D biomaterial scaffolds and osteogenesis. , 2005, Biomaterials.

[134]  Gero Decher,et al.  Fuzzy Nanoassemblies: Toward Layered Polymeric Multicomposites , 1997 .

[135]  Julien Bras,et al.  Cellulosic Bionanocomposites: A Review of Preparation, Properties and Applications , 2010 .

[136]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[137]  Kentaro Abe,et al.  Review: current international research into cellulose nanofibres and nanocomposites , 2010, Journal of Materials Science.

[138]  Juming Yao,et al.  Electrospinning of Bombyx mori silk fibroin nanofiber mats reinforced by cellulose nanowhiskers , 2011 .

[139]  Matthew P. Brennan,et al.  Small-diameter biodegradable scaffolds for functional vascular tissue engineering in the mouse model. , 2008, Biomaterials.

[140]  Kerm Sin Chian,et al.  In vitro cell infiltration and in vivo cell infiltration and vascularization in a fibrous, highly porous poly(D,L-lactide) scaffold fabricated by cryogenic electrospinning technique. , 2009, Journal of biomedical materials research. Part A.

[141]  Eileen Ingham,et al.  Production of self-assembling biomaterials for tissue engineering , 2009, Trends in biotechnology.

[142]  S. Kuga,et al.  Effect of Trace Electrolyte on Liquid Crystal Type of Cellulose Microcrystals , 2001 .

[143]  E. J. Foster,et al.  Bionanocomposites: differential effects of cellulose nanocrystals on protein diblock copolymers. , 2013, Biomacromolecules.

[144]  J. Loo,et al.  Collagen–cellulose composite thin films that mimic soft-tissue and allow stem-cell orientation , 2013, Journal of Materials Science: Materials in Medicine.

[145]  David G Simpson,et al.  Nanofiber technology: designing the next generation of tissue engineering scaffolds. , 2007, Advanced drug delivery reviews.

[146]  M. Wolcott,et al.  Thermal and mechanical properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/cellulose nanowhiskers composites , 2010 .

[147]  M. Maniruzzaman,et al.  Cellulose nanocrystals extracted from okra fibers in PVA nanocomposites , 2013 .

[148]  Xiabin Jing,et al.  Biodegradable synthetic polymers: Preparation, functionalization and biomedical application , 2012 .

[149]  P. Dubois,et al.  Bionanocomposites based on poly(ε-caprolactone)-grafted cellulose nanocrystals by ring-opening polymerization , 2008 .

[150]  Chikara Ohtsuki,et al.  The controlled resorption of porous α-tricalcium phosphate using a hydroxypropylcellulose coating , 2004, Journal of materials science. Materials in medicine.

[151]  A. Ragauskas,et al.  Improving the mechanical and thermal properties of gelatin hydrogels cross-linked by cellulose nanowhiskers. , 2013, Carbohydrate polymers.

[152]  A. Dufresne,et al.  Plasticized Starch/Tunicin Whiskers Nanocomposite Materials. 2. Mechanical Behavior , 2001 .

[153]  R. Venditti,et al.  Reinforcing poly(epsilon-caprolactone) nanofibers with cellulose nanocrystals. , 2009, ACS applied materials & interfaces.

[154]  Dieter Klemm,et al.  Nanocelluloses: a new family of nature-based materials. , 2011, Angewandte Chemie.

[155]  Min Sung Kim,et al.  Nanotopography-guided tissue engineering and regenerative medicine. , 2013, Advanced drug delivery reviews.

[156]  Peter X. Ma,et al.  Scaffolds for tissue fabrication , 2004 .

[157]  A. Khademhosseini,et al.  Engineering Approaches Toward Deconstructing and Controlling the Stem Cell Environment , 2011, Annals of Biomedical Engineering.

[158]  Albert J. Keung,et al.  Presentation counts: microenvironmental regulation of stem cells by biophysical and material cues. , 2010, Annual review of cell and developmental biology.

[159]  R. Pecora,et al.  Translational and Rotational Dynamics of Rodlike Cellulose Whiskers , 2003 .

[160]  Xueming Zhang,et al.  Synthesis and characterization of mechanically flexible and tough cellulose nanocrystals–polyacrylamide nanocomposite hydrogels , 2013, Cellulose.

[161]  Y. Tu,et al.  Nanotechnology in the regulation of stem cell behavior , 2013, Science and technology of advanced materials.

[162]  Juming Yao,et al.  Fabrication and characterization of silk fibroin/poly(ethylene glycol)/cellulose nanowhisker composite films , 2012 .

[163]  K. Jacob,et al.  Design of a cellulose-based nanocomposite as a potential polymeric scaffold in tissue engineering , 2013 .

[164]  E. Cranston,et al.  Injectable polysaccharide hydrogels reinforced with cellulose nanocrystals: morphology, rheology, degradation, and cytotoxicity. , 2013, Biomacromolecules.

[165]  Dehong Hu,et al.  Potential of nanocrystalline cellulose-fibrin nanocomposites for artificial vascular graft applications. , 2013, Biomacromolecules.

[166]  W. Thielemans,et al.  Biodegradability of organic nanoparticles in the aqueous environment. , 2011, Chemosphere.

[167]  Peter X Ma,et al.  Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering. , 2004, Biomaterials.

[168]  David J Mooney,et al.  New materials for tissue engineering: towards greater control over the biological response. , 2008, Trends in biotechnology.

[169]  Patrick J. Schexnailder,et al.  Nanocomposite polymer hydrogels , 2009 .

[170]  C. Rudd,et al.  Effect of cellulose nanowhiskers on surface morphology, mechanical properties, and cell adhesion of melt-drawn polylactic Acid fibers. , 2014, Biomacromolecules.

[171]  Z. Qin,et al.  Comparison of the reinforcing effects for cellulose nanocrystals obtained by sulfuric and hydrochloric acid hydrolysis on the mechanical and thermal properties of bacterial polyester , 2013 .

[172]  K. Woodhouse,et al.  Understanding the biodegradation of polyurethanes: from classical implants to tissue engineering materials. , 2005, Biomaterials.

[173]  M. Roman,et al.  Effect of reaction conditions on the properties and behavior of wood cellulose nanocrystal suspensions. , 2005, Biomacromolecules.

[174]  M. Wolcott,et al.  Crystallization kinetics of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/cellulose nanowhiskers composites. , 2012, Carbohydrate polymers.

[175]  R. Hopkins,et al.  Wet spun microfibers: potential in the design of controlled-release scaffolds? , 2013, Therapeutic delivery.

[176]  K. Dreher,et al.  Health and environmental impact of nanotechnology: toxicological assessment of manufactured nanoparticles. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[177]  I. Burgert,et al.  Reorientation of cellulose nanowhiskers in agarose hydrogels under tensile loading. , 2012, Biomacromolecules.

[178]  E. Ureña-Benavides,et al.  Wide-Angle X-ray Diffraction of Cellulose Nanocrystal−Alginate Nanocomposite Fibers , 2011 .

[179]  Junji Sugiyama,et al.  Orientation of cellulose microcrystals by strong magnetic fields , 1992 .

[180]  S. Eichhorn,et al.  Bacterial cellulose scaffolds and cellulose nanowhiskers for tissue engineering. , 2013, Nanomedicine.

[181]  A. Dufresne,et al.  Plasticized Starch/Tunicin Whiskers Nanocomposites. 1. Structural Analysis , 2000 .

[182]  C. Santulli,et al.  Binary PVA bio-nanocomposites containing cellulose nanocrystals extracted from different natural sources: part I. , 2013, Carbohydrate polymers.

[183]  J. P. de Mesquita,et al.  Biobased nanocomposites from layer-by-layer assembly of cellulose nanowhiskers with chitosan. , 2010, Biomacromolecules.

[184]  C. Chua,et al.  Foreword. Advanced nanobiomaterials for tissue engineering and regenerative medicine. , 2013, Nanomedicine.

[185]  Alain Dufresne,et al.  Review of recent research into cellulosic whiskers, their properties and their application in nanocomposite field. , 2005, Biomacromolecules.

[186]  Peter X Ma,et al.  Biomimetic materials for tissue engineering. , 2008, Advanced drug delivery reviews.

[187]  K. Shanmuganathan,et al.  Biologically inspired hierarchical design of nanocomposites based on poly(ethylene oxide) and cellulose nanofibers. , 2011, Macromolecular rapid communications.

[188]  E. Place,et al.  Complexity in biomaterials for tissue engineering. , 2009, Nature materials.

[189]  Brian O'Connor,et al.  An ecotoxicological characterization of nanocrystalline cellulose (NCC) , 2010, Nanotoxicology.

[190]  Christopher S. Chen Mechanotransduction – a field pulling together? , 2008, Journal of Cell Science.

[191]  A. Dufresne,et al.  TEMPO-oxidized nanocellulose participating as crosslinking aid for alginate-based sponges. , 2012, ACS applied materials & interfaces.

[192]  Wadood Y. Hamad,et al.  On the Development and Applications of Cellulosic Nanofibrillar and Nanocrystalline Materials , 2008 .

[193]  Kristi S Anseth,et al.  Advances in bioactive hydrogels to probe and direct cell fate. , 2012, Annual review of chemical and biomolecular engineering.

[194]  P. Lu,et al.  Preparation and characterization of cellulose nanocrystals from rice straw. , 2012, Carbohydrate polymers.

[195]  J. Luong,et al.  Probing inhibitory effects of nanocrystalline cellulose: inhibition versus surface charge. , 2012, Nanoscale.

[196]  P. Zavattieri,et al.  Anisotropy of the elastic properties of crystalline cellulose Iβ from first principles density functional theory with Van der Waals interactions , 2013, Cellulose.

[197]  A. Atala,et al.  Carbon nanotube applications for tissue engineering. , 2007, Biomaterials.

[198]  N. Gadegaard,et al.  Nanoscale surfaces for the long-term maintenance of mesenchymal stem cell phenotype and multipotency. , 2011, Nature materials.

[199]  S. Kundu,et al.  Electrospinning: a fascinating fiber fabrication technique. , 2010, Biotechnology advances.

[200]  João F. Mano,et al.  Polymer/bioactive glass nanocomposites for biomedical applications: A review , 2010 .

[201]  D. Klemm,et al.  Cellulose: fascinating biopolymer and sustainable raw material. , 2005, Angewandte Chemie.

[202]  Antonios G Mikos,et al.  Polymeric nanofibers in tissue engineering. , 2011, Tissue engineering. Part B, Reviews.

[203]  Yi Jiang,et al.  Topography of Extracellular Matrix Mediates Vascular Morphogenesis and Migration Speeds in Angiogenesis , 2009, PLoS Comput. Biol..

[204]  Sheryl E. Philip,et al.  Comparison of nanoscale and microscale bioactive glass on the properties of P(3HB)/Bioglass composites. , 2008, Biomaterials.

[205]  Younan Xia,et al.  Electrospinning of Nanofibers: Reinventing the Wheel? , 2004 .

[206]  Yixiang Wang,et al.  Impacts of nanowhisker on formation kinetics and properties of all-cellulose composite gels , 2011 .

[207]  R. Oréfice,et al.  Increasing the elongation at break of polyhydroxybutyrate biopolymer: Effect of cellulose nanowhiskers on mechanical and thermal properties , 2013 .

[208]  Shuping Dong,et al.  CYTOTOXICITY AND CELLULAR UPTAKE OF CELLULOSE NANOCRYSTALS , 2012 .

[209]  Molly M Stevens,et al.  Synthetic polymer scaffolds for tissue engineering. , 2009, Chemical Society reviews.

[210]  Jingquan Han,et al.  High-water-content mouldable polyvinyl alcohol-borax hydrogels reinforced by well-dispersed cellulose nanoparticles: dynamic rheological properties and hydrogel formation mechanism. , 2014, Carbohydrate polymers.

[211]  Kadriye Tuzlakoglu,et al.  Biodegradable polymeric fiber structures in tissue engineering. , 2009, Tissue engineering. Part B, Reviews.

[212]  R. Reis,et al.  Bionanocomposites from lignocellulosic resources: Properties, applications and future trends for their use in the biomedical field , 2013 .

[213]  Chengjun Zhou,et al.  Electrospun bio-nanocomposite scaffolds for bone tissue engineering by cellulose nanocrystals reinforcing maleic anhydride grafted PLA. , 2013, ACS applied materials & interfaces.

[214]  A. Mikos,et al.  Electrospun poly(epsilon-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. , 2006, Biomacromolecules.

[215]  T. Quinn,et al.  Reinforcement with cellulose nanocrystals of poly(vinyl alcohol) hydrogels prepared by cyclic freezing and thawing , 2011 .

[216]  C. Rudd,et al.  Physico-chemical and mechanical properties of nanocomposites prepared using cellulose nanowhiskers and poly(lactic acid) , 2011, Journal of Materials Science.

[217]  Mikhail V. Levit,et al.  Freeze-casting of cellulose nanowhisker foams prepared from a water-dimethylsulfoxide (DMSO) binary mixture at low DMSO concentrations , 2013 .

[218]  Dietmar Werner Hutmacher,et al.  How smart do biomaterials need to be? A translational science and clinical point of view. , 2013, Advanced drug delivery reviews.

[219]  Chengjun Zhou,et al.  Application of rod-shaped cellulose nanocrystals in polyacrylamide hydrogels. , 2011, Journal of colloid and interface science.

[220]  Z. Qin,et al.  Green Nanocomposites Based on Functionalized Cellulose Nanocrystals: A Study on the Relationship between Interfacial Interaction and Property Enhancement , 2014 .

[221]  Jason A. Burdick,et al.  Engineering ECM signals into biomaterials , 2012 .

[222]  A. Boccaccini,et al.  Characterization of carbon nanotube (MWCNT) containing P(3HB)/bioactive glass composites for tissue engineering applications. , 2010, Acta biomaterialia.

[223]  M. Wada,et al.  Mechanical properties of Silk fibroin-microcrystalline cellulose composite films , 2002 .

[224]  S. Eichhorn,et al.  Orientation and deformation of wet-stretched all-cellulose nanocomposites , 2013, Journal of Materials Science.

[225]  D. Petri,et al.  Hybrid layer-by-layer assembly based on animal and vegetable structural materials: multilayered films of collagen and cellulose nanowhiskers , 2011 .

[226]  E. J. Foster,et al.  Investigating the interaction of cellulose nanofibers derived from cotton with a sophisticated 3D human lung cell coculture. , 2011, Biomacromolecules.