Development of hydrogels for regenerative engineering

The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano‐ and micro‐technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell‐matrix interactions at the nanoscale. With this perspective, this review discusses the most commonly used hydrogel materials and their fabrication strategies for regenerative engineering. We highlight the physical, chemical, and functional modulation of hydrogels to design and engineer biomimetic tissues based on recent achievements in nano‐ and micro‐technologies. In addition, current hydrogel‐based regenerative engineering strategies for treating multiple tissues, such as musculoskeletal, nervous and cardiac tissue, are also covered in this review. The interaction of multiple disciplines including materials science, cell biology, and chemistry, will further play an important role in the design of functional hydrogels for the regeneration of complex tissues.

[1]  Brendon M. Baker,et al.  Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues , 2012 .

[2]  Dai Fukumura,et al.  Engineering vascularized tissue , 2005, Nature Biotechnology.

[3]  Jason A Burdick,et al.  Moving from static to dynamic complexity in hydrogel design , 2012, Nature Communications.

[4]  Ali Khademhosseini,et al.  Hydrogels and microtechnologies for engineering the cellular microenvironment. , 2012, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[5]  C. McCormick,et al.  Thermoreversible hydrogels from RAFT-synthesized BAB triblock copolymers: steps toward biomimetic matrices for tissue regeneration. , 2008, Biomacromolecules.

[6]  K J Halbhuber,et al.  Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves. , 2003, Journal of structural biology.

[7]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[8]  Anthony Atala,et al.  3D bioprinting of tissues and organs , 2014, Nature Biotechnology.

[9]  Liang Zhao,et al.  An injectable calcium phosphate-alginate hydrogel-umbilical cord mesenchymal stem cell paste for bone tissue engineering. , 2010, Biomaterials.

[10]  S. Heilshorn,et al.  Adaptable Hydrogel Networks with Reversible Linkages for Tissue Engineering , 2015, Advanced materials.

[11]  Bernadette A. Thomas,et al.  Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 , 2015, The Lancet.

[12]  Milica Radisic,et al.  Topological and electrical control of cardiac differentiation and assembly , 2013, Stem Cell Research & Therapy.

[13]  A. Hoffman,et al.  PEG-cross-linked heparin is an affinity hydrogel for sustained release of vascular endothelial growth factor , 2006, Journal of biomaterials science. Polymer edition.

[14]  G. Ciardelli,et al.  Gelatin‐based hydrogel for vascular endothelial growth factor release in peripheral nerve tissue engineering , 2017, Journal of tissue engineering and regenerative medicine.

[15]  A. Khademhosseini,et al.  Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs Using Low‐Viscosity Bioink , 2016, Advanced materials.

[16]  T. Matsuda,et al.  Photo-iniferter-based thermoresponsive block copolymers composed of poly(ethylene glycol) and poly(N-isopropylacrylamide) and chondrocyte immobilization. , 2006, Biomaterials.

[17]  A K Capulli,et al.  Fibrous scaffolds for building hearts and heart parts. , 2016, Advanced drug delivery reviews.

[18]  N. Ferrara Binding to the Extracellular Matrix and Proteolytic Processing: Two Key Mechanisms Regulating Vascular Endothelial Growth Factor Action , 2010, Molecular biology of the cell.

[19]  Sanjay Kumar,et al.  Biofunctionalization of Hydrogels for Engineering the Cellular Microenvironment , 2014 .

[20]  A. Khademhosseini,et al.  Cell‐laden Microengineered and Mechanically Tunable Hybrid Hydrogels of Gelatin and Graphene Oxide , 2013, Advanced materials.

[21]  M. Goto,et al.  Enzymatically prepared redox‐responsive hydrogels as potent matrices for hepatocellular carcinoma cell spheroid formation , 2016, Biotechnology journal.

[22]  M. Shoichet,et al.  Differentiation of neural stem cells in three-dimensional growth factor-immobilized chitosan hydrogel scaffolds. , 2011, Biomaterials.

[23]  C. Rider Heparin/heparan sulphate binding in the TGF-β cytokine superfamily , 2006 .

[24]  Michiya Matsusaki,et al.  Novel functional biodegradable polymer IV: pH-sensitive controlled release of fibroblast growth factor-2 from a poly(gamma-glutamic acid)-sulfonate matrix for tissue engineering. , 2005, Biomacromolecules.

[25]  Covalently tethered transforming growth factor beta in PEG hydrogels promotes chondrogenic differentiation of encapsulated human mesenchymal stem cells , 2012, Drug Delivery and Translational Research.

[26]  J. Werkmeister,et al.  Bone regeneration using photocrosslinked hydrogel incorporating rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles. , 2014, Biomaterials.

[27]  Christopher N. Bowman,et al.  Relative reactivity and selectivity of vinyl sulfones and acrylates towards the thiol–Michael addition reaction and polymerization , 2013 .

[28]  J. Klawitter,et al.  Application of porous ceramics for the attachment of load bearing internal orthopedic applications , 1971 .

[29]  F. Liu,et al.  In vitro selection of novel RNA ligands that bind human cytomegalovirus and block viral infection. , 2000, RNA.

[30]  A. Khademhosseini,et al.  Carbon nanotube reinforced hybrid microgels as scaffold materials for cell encapsulation. , 2012, ACS nano.

[31]  Amir A. Zadpoor,et al.  Additive Manufacturing of Biomaterials, Tissues, and Organs , 2016, Annals of Biomedical Engineering.

[32]  A. Smerieri,et al.  Improved scaffold biocompatibility through anti-Fibronectin aptamer functionalization. , 2016, Acta biomaterialia.

[33]  Z. Qian,et al.  Synthesis, characterization, and application of reversible PDLLA-PEG-PDLLA copolymer thermogels in vitro and in vivo , 2016, Scientific Reports.

[34]  杨朝勇 Aptamers evolved from live cells as effective molecular probes for cancer study , 2006 .

[35]  P. Genever,et al.  Collagen-Poly(N-isopropylacrylamide) Hydrogels with Tunable Properties. , 2016, Biomacromolecules.

[36]  Matthew S. Rehmann,et al.  Tunable and dynamic soft materials for three-dimensional cell culture , 2013, Soft matter.

[37]  Martin Ehrbar,et al.  Cell‐demanded release of VEGF from synthetic, biointeractive cell‐ingrowth matrices for vascularized tissue growth , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[38]  M. Kurisawa,et al.  Injectable biodegradable hydrogels: progress and challenges. , 2013, Journal of materials chemistry. B.

[39]  Yining Wang,et al.  Synthesis and characterization of an injectable and self-curing poly(methyl methacrylate) cement functionalized with a biomimetic chitosan–poly(vinyl alcohol)/nano-sized hydroxyapatite/silver hydrogel , 2016 .

[40]  H. Kim,et al.  Collagen hydrogels incorporated with surface-aminated mesoporous nanobioactive glass: Improvement of physicochemical stability and mechanical properties is effective for hard tissue engineering. , 2013, Acta biomaterialia.

[41]  Jun Lin,et al.  Up-conversion cell imaging and pH-induced thermally controlled drug release from NaYF4/Yb3+/Er3+@hydrogel core-shell hybrid microspheres. , 2012, ACS nano.

[42]  J. Feijen,et al.  Release of model proteins and basic fibroblast growth factor from in situ forming degradable dextran hydrogels. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[43]  R. C. Johnson,et al.  Neovascularization of synthetic membranes directed by membrane microarchitecture. , 1995, Journal of biomedical materials research.

[44]  C. van Nostrum,et al.  Novel crosslinking methods to design hydrogels. , 2002, Advanced drug delivery reviews.

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

[46]  X Chris Le,et al.  Selection of aptamers against live bacterial cells. , 2008, Analytical chemistry.

[47]  Horst Kessler,et al.  RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. , 2003, Biomaterials.

[48]  R. McLemore,et al.  In situ forming, resorbable graft copolymer hydrogels providing controlled drug release. , 2013, Journal of biomedical materials research. Part A.

[49]  D. Mooney,et al.  Alginate: properties and biomedical applications. , 2012, Progress in polymer science.

[50]  Yong Wang,et al.  Aptamer-functionalized superporous hydrogels for sequestration and release of growth factors regulated via molecular recognition. , 2014, Biomaterials.

[51]  Yong Wang,et al.  Aptamer-functionalized in situ injectable hydrogel for controlled protein release. , 2010, Biomacromolecules.

[52]  R. Marchant,et al.  Design properties of hydrogel tissue-engineering scaffolds , 2011, Expert review of medical devices.

[53]  David J. Mooney,et al.  Harnessing Traction-Mediated Manipulation of the Cell-Matrix Interface to Control Stem Cell Fate , 2010, Nature materials.

[54]  Steven C George,et al.  Prevascularization of a fibrin-based tissue construct accelerates the formation of functional anastomosis with host vasculature. , 2009, Tissue engineering. Part A.

[55]  Cindi M Morshead,et al.  Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels. , 2011, Nature materials.

[56]  Wutian Wu,et al.  Functional Self-Assembling Peptide Nanofiber Hydrogels Designed for Nerve Degeneration. , 2016, ACS applied materials & interfaces.

[57]  You-Lo Hsieh,et al.  Ultra-fine polyelectrolyte hydrogel fibres from poly(acrylic acid)/poly(vinyl alcohol) , 2005 .

[58]  Ali Khademhosseini,et al.  Direct 3D bioprinting of perfusable vascular constructs using a blend bioink. , 2016, Biomaterials.

[59]  Cynthia A. Reinhart-King,et al.  Tensional homeostasis and the malignant phenotype. , 2005, Cancer cell.

[60]  Nic D. Leipzig,et al.  In vivo assessment of guided neural stem cell differentiation in growth factor immobilized chitosan-based hydrogel scaffolds. , 2014, Biomaterials.

[61]  Brendon M. Baker,et al.  Cell-mediated fiber recruitment drives extracellular matrix mechanosensing in engineered fibrillar microenvironments , 2015, Nature materials.

[62]  Edward S Boyden,et al.  Simple Precision Creation of Digitally Specified, Spatially Heterogeneous, Engineered Tissue Architectures , 2013, Advanced materials.

[63]  Alexander Revzin,et al.  Heparin-based hydrogel as a matrix for encapsulation and cultivation of primary hepatocytes. , 2010, Biomaterials.

[64]  Rocky S Tuan,et al.  Multilayered polycaprolactone/gelatin fiber-hydrogel composite for tendon tissue engineering. , 2016, Acta biomaterialia.

[65]  Ali Khademhosseini,et al.  3D Bioprinting for Tissue and Organ Fabrication , 2016, Annals of Biomedical Engineering.

[66]  Jay C. Sy,et al.  Maleimide Cross‐Linked Bioactive PEG Hydrogel Exhibits Improved Reaction Kinetics and Cross‐Linking for Cell Encapsulation and In Situ Delivery , 2012, Advanced materials.

[67]  Jason A Burdick,et al.  Nanofibrous Hydrogels with Spatially Patterned Biochemical Signals to Control Cell Behavior , 2015, Advanced materials.

[68]  Bernadette A. Thomas,et al.  Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 , 2015, The Lancet.

[69]  Deok‐Ho Kim,et al.  Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink , 2014, Nature Communications.

[70]  Tal Dvir,et al.  Tissue engineering on the nanoscale: lessons from the heart. , 2013, Current opinion in biotechnology.

[71]  Santanu Dhara,et al.  Stimulus-Responsive, Biodegradable, Biocompatible, Covalently Cross-Linked Hydrogel Based on Dextrin and Poly(N-isopropylacrylamide) for in Vitro/in Vivo Controlled Drug Release. , 2015, ACS applied materials & interfaces.

[72]  S. Yoo,et al.  Creating perfused functional vascular channels using 3D bio-printing technology. , 2014, Biomaterials.

[73]  Younan Xia,et al.  Electrospun Nanofibers for Regenerative Medicine , 2012, Advanced healthcare materials.

[74]  Hossein Hosseinkhani,et al.  Self-assembled proteins and peptides for regenerative medicine. , 2013, Chemical reviews.

[75]  C. Werner,et al.  FGF-2 and VEGF functionalization of starPEG-heparin hydrogels to modulate biomolecular and physical cues of angiogenesis. , 2010, Biomaterials.

[76]  L. Claesson‐Welsh,et al.  Heparin Amplifies Platelet-derived Growth Factor (PDGF)- BB-induced PDGF α-Receptor but Not PDGF β-Receptor Tyrosine Phosphorylation in Heparan Sulfate-deficient Cells , 2002, The Journal of Biological Chemistry.

[77]  J. Hubbell,et al.  Enhanced proteolytic degradation of molecularly engineered PEG hydrogels in response to MMP-1 and MMP-2. , 2010, Biomaterials.

[78]  Ali Khademhosseini,et al.  Hierarchical Fabrication of Engineered Vascularized Bone Biphasic Constructs via Dual 3D Bioprinting: Integrating Regional Bioactive Factors into Architectural Design , 2016, Advanced healthcare materials.

[79]  Alessandro Giacomello,et al.  Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction. , 2015, Biomaterials.

[80]  R. Hajjar,et al.  Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair , 2007, Nature Medicine.

[81]  A. López-Requena,et al.  In vivo site-specific biotinylation of proteins within the secretory pathway using a single vector system , 2008, BMC biotechnology.

[82]  G. Schreiber Methods for studying the interaction of barnase with its inhibitor barstar. , 2001, Methods in molecular biology.

[83]  H. Low,et al.  Planar and tubular patterning of micro and nano-topographies on poly(vinyl alcohol) hydrogel for improved endothelial cell responses. , 2016, Biomaterials.

[84]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[85]  Sébastien Perrier,et al.  Smart hybrid materials by conjugation of responsive polymers to biomacromolecules. , 2015, Nature materials.

[86]  G. Schneider,et al.  Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[87]  A. Khademhosseini,et al.  Hydrogels in Regenerative Medicine , 2009, Advanced materials.

[88]  Yanfei Xu,et al.  Genipin cross-linked decellularized tracheal tubular matrix for tracheal tissue engineering applications , 2016, Scientific Reports.

[89]  Harald C Ott,et al.  Organ engineering based on decellularized matrix scaffolds. , 2011, Trends in molecular medicine.

[90]  J. Lewis,et al.  3D Bioprinting of Vascularized, Heterogeneous Cell‐Laden Tissue Constructs , 2014, Advanced materials.

[91]  C. Mason,et al.  A brief definition of regenerative medicine. , 2008, Regenerative medicine.

[92]  A. Mikos,et al.  In vitro and in vivo evaluation of self-mineralization and biocompatibility of injectable, dual-gelling hydrogels for bone tissue engineering. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[93]  Robert J. Linhardt,et al.  Heparin—Protein Interactions , 2002 .

[94]  A. Rich,et al.  Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[95]  K. Christman,et al.  Controlling stem cell behavior with decellularized extracellular matrix scaffolds. , 2016, Current opinion in solid state & materials science.

[96]  Manish K Jaiswal,et al.  Bioactive nanoengineered hydrogels for bone tissue engineering: a growth-factor-free approach. , 2015, ACS nano.

[97]  Yong Wang,et al.  Chimeric Aptamer-Gelatin Hydrogels as an Extracellular Matrix Mimic for Loading Cells and Growth Factors. , 2016, Biomacromolecules.

[98]  Antonios G Mikos,et al.  Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair. , 2014, Biomaterials.

[99]  Wei Sun,et al.  Bioprinting three-dimensional cell-laden tissue constructs with controllable degradation , 2016, Scientific Reports.

[100]  U. Krishnan,et al.  The Integration of Nanotechnology and Biology for Cell Engineering: Promises and Challenges , 2013 .

[101]  Ali Khademhosseini,et al.  3D biofabrication strategies for tissue engineering and regenerative medicine. , 2014, Annual review of biomedical engineering.

[102]  Ali Khademhosseini,et al.  Engineering microscale topographies to control the cell-substrate interface. , 2012, Biomaterials.

[103]  Brian Derby,et al.  Printing and Prototyping of Tissues and Scaffolds , 2012, Science.

[104]  J. Park,et al.  Freestanding stacked mesh-like hydrogel sheets enable the creation of complex macroscale cellular scaffolds. , 2016, Biotechnology journal.

[105]  P. Carmeliet,et al.  VEGF-loaded injectable hydrogel enhances plasticity in the injured spinal cord , 2013 .

[106]  James C. Weaver,et al.  Hydrogels with tunable stress relaxation regulate stem cell fate and activity , 2015, Nature materials.

[107]  K. Anseth,et al.  Synthetic hydrogel niches that promote hMSC viability. , 2005, Matrix biology : journal of the International Society for Matrix Biology.

[108]  Akhilesh K. Gaharwar,et al.  Mechanically Stiff Nanocomposite Hydrogels at Ultralow Nanoparticle Content. , 2016, ACS nano.

[109]  Uma Maheswari Krishnan,et al.  Electrospun Nanofibers as Scaffolds for Skin Tissue Engineering , 2014 .

[110]  K. Anseth,et al.  Spatially patterned matrix elasticity directs stem cell fate , 2016, Proceedings of the National Academy of Sciences.

[111]  Ali Khademhosseini,et al.  Controlling the porosity and microarchitecture of hydrogels for tissue engineering. , 2010, Tissue engineering. Part B, Reviews.

[112]  Jos Malda,et al.  Reinforcement of hydrogels using three-dimensionally printed microfibres , 2015, Nature Communications.

[113]  Mingzhu Liu,et al.  Preparation and controlled degradation of oxidized sodium alginate hydrogel , 2009 .

[114]  Yan Zhang,et al.  Engineering Nanoscale Stem Cell Niche: Direct Stem Cell Behavior at Cell–Matrix Interface , 2015, Advanced healthcare materials.

[115]  M. Shoichet,et al.  A covalently modified hydrogel blend of hyaluronan–methyl cellulose with peptides and growth factors influences neural stem/progenitor cell fate , 2012 .

[116]  Jussi Taipale,et al.  Growth factors in the extracellular matrix , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[117]  A. E. El Haj,et al.  Sustained PDGF-BB release from PHBHHx loaded nanoparticles in 3D hydrogel/stem cell model. , 2015, Journal of biomedical materials research. Part A.

[118]  C H Heldin,et al.  Inhibitory DNA ligands to platelet-derived growth factor B-chain. , 1996, Biochemistry.

[119]  A. J. Grodzinsky,et al.  Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: Implications for cartilage tissue repair , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[120]  Jennifer L West,et al.  Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration. , 2005, Biomaterials.

[121]  Ali Khademhosseini,et al.  Electrospun scaffolds for tissue engineering of vascular grafts. , 2014, Acta biomaterialia.

[122]  J. Yeh,et al.  Effect of hydroxyapatite particles on the rheological behavior of poly(ethylene glycol)-poly(lactic-co-glycolic acid) thermosensitive hydrogels , 2015 .

[123]  R. J. McMurtrey Patterned and functionalized nanofiber scaffolds in three-dimensional hydrogel constructs enhance neurite outgrowth and directional control , 2014, Journal of neural engineering.

[124]  C. Laurencin,et al.  Regenerative Engineering , 2012, Science Translational Medicine.

[125]  Yang Liu,et al.  A self-assembling peptide reduces glial scarring, attenuates post-traumatic inflammation and promotes neurological recovery following spinal cord injury. , 2013, Acta biomaterialia.

[126]  D. Rifkin,et al.  Interaction of heparin with human basic fibroblast growth factor: Protection of the angiogenic protein from proteolytic degradation by a glycosaminoglycan , 1989, Journal of cellular physiology.

[127]  D. Melton,et al.  Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[128]  James J. Yoo,et al.  Bioprinted Amniotic Fluid‐Derived Stem Cells Accelerate Healing of Large Skin Wounds , 2012, Stem cells translational medicine.

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

[130]  Guillaume Charras,et al.  Physical influences of the extracellular environment on cell migration , 2014, Nature Reviews Molecular Cell Biology.

[131]  Eben Alsberg,et al.  Photofunctionalization of alginate hydrogels to promote adhesion and proliferation of human mesenchymal stem cells. , 2013, Tissue engineering. Part A.

[132]  Mikaël M. Martino,et al.  In Situ Cell Manipulation through Enzymatic Hydrogel Photopatterning , 2013 .

[133]  Chaenyung Cha,et al.  25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine , 2014, Advanced materials.

[134]  Atu Agawu,et al.  An in situ forming collagen-PEG hydrogel for tissue regeneration. , 2012, Acta biomaterialia.

[135]  Cato T Laurencin,et al.  Micro- and nanofabrication of chitosan structures for regenerative engineering. , 2014, Acta biomaterialia.

[136]  J. West,et al.  Effects of Epidermal Growth Factor on Fibroblast Migration through Biomimetic Hydrogels , 2003, Biotechnology progress.

[137]  Silviya P Zustiak,et al.  Hydrolytically degradable poly(ethylene glycol) hydrogel scaffolds with tunable degradation and mechanical properties. , 2010, Biomacromolecules.

[138]  M. Yamada,et al.  Fabrication of multilayered vascular tissues using microfluidic agarose hydrogel platforms , 2016, Biotechnology journal.

[139]  Joydip Kundu,et al.  Decellularized retinal matrix: Natural platforms for human retinal progenitor cell culture. , 2016, Acta biomaterialia.

[140]  Murat Guvendiren,et al.  Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics , 2012, Nature Communications.

[141]  A. Khademhosseini,et al.  Bioactive Silicate Nanoplatelets for Osteogenic Differentiation of Human Mesenchymal Stem Cells , 2013, Advanced materials.

[142]  Y. S. Zhang,et al.  Reduced Graphene Oxide-GelMA Hybrid Hydrogels as Scaffolds for Cardiac Tissue Engineering. , 2016, Small.

[143]  Diane Hoffman-Kim,et al.  Topography, cell response, and nerve regeneration. , 2010, Annual review of biomedical engineering.

[144]  Carsten Werner,et al.  A star-PEG-heparin hydrogel platform to aid cell replacement therapies for neurodegenerative diseases. , 2009, Biomaterials.

[145]  Wesley R. Legant,et al.  Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels , 2013, Nature materials.

[146]  Douglas A Lauffenburger,et al.  Microarchitecture of three-dimensional scaffolds influences cell migration behavior via junction interactions. , 2008, Biophysical journal.

[147]  Thomas Hankemeier,et al.  Microfluidic 3D cell culture: from tools to tissue models. , 2015, Current opinion in biotechnology.

[148]  Edward Y Lee,et al.  Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[149]  Wutian Wu,et al.  Three-Dimensional Nanofiber Hybrid Scaffold Directs and Enhances Axonal Regeneration after Spinal Cord Injury. , 2016, ACS biomaterials science & engineering.

[150]  M. Tuszynski,et al.  Freeze-dried agarose scaffolds with uniaxial channels stimulate and guide linear axonal growth following spinal cord injury. , 2006, Biomaterials.

[151]  Christopher D Spicer,et al.  Selective chemical protein modification , 2014, Nature Communications.

[152]  Zu-wei Ma,et al.  Thermally responsive injectable hydrogel incorporating methacrylate-polylactide for hydrolytic lability. , 2010, Biomacromolecules.

[153]  Marcel A. Heinrich,et al.  Rapid Continuous Multimaterial Extrusion Bioprinting , 2017, Advanced materials.

[154]  Robert Langer,et al.  Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation , 1999, The Lancet.

[155]  V. Truong,et al.  In situ-forming robust chitosan-poly(ethylene glycol) hydrogels prepared by copper-free azide-alkyne click reaction for tissue engineering. , 2014, Biomaterials science.

[156]  Mark A. Skylar-Scott,et al.  Three-dimensional bioprinting of thick vascularized tissues , 2016, Proceedings of the National Academy of Sciences.

[157]  L. Pellegrini,et al.  Role of heparan sulfate in fibroblast growth factor signalling: a structural view. , 2001, Current opinion in structural biology.

[158]  C. Rider Heparin/heparan sulphate binding in the TGF-beta cytokine superfamily. , 2006, Biochemical Society transactions.

[159]  Xiaofeng Cui,et al.  Inkjet-bioprinted acrylated peptides and PEG hydrogel with human mesenchymal stem cells promote robust bone and cartilage formation with minimal printhead clogging. , 2015, Biotechnology journal.

[160]  Jing Zhang,et al.  Synthesis and Characterization of pH- and Temperature-Sensitive Poly(methacrylic acid)/Poly(N-isopropylacrylamide) Interpenetrating Polymeric Networks , 2000 .

[161]  A. Khademhosseini,et al.  Highly Elastic Micropatterned Hydrogel for Engineering Functional Cardiac Tissue , 2013, Advanced functional materials.

[162]  Yong Wang,et al.  Hydrogel functionalization with DNA aptamers for sustained PDGF-BB release. , 2010, Chemical communications.

[163]  David F Williams,et al.  Neural tissue engineering options for peripheral nerve regeneration. , 2014, Biomaterials.

[164]  Junmin Zhu,et al.  Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. , 2010, Biomaterials.

[165]  S. Rizzi,et al.  Elucidating the role of matrix stiffness in 3D cell migration and remodeling. , 2011, Biophysical journal.

[166]  Robert L Sah,et al.  Tissue engineering of articular cartilage with biomimetic zones. , 2009, Tissue engineering. Part B, Reviews.

[167]  Changyong Wang,et al.  A chitosan-glutathione based injectable hydrogel for suppression of oxidative stress damage in cardiomyocytes. , 2013, Biomaterials.

[168]  M. Nikkhah,et al.  3D Cardiac Microtissues Encapsulated with the Co‐Culture of Cardiomyocytes and Cardiac Fibroblasts , 2015, Advanced healthcare materials.

[169]  Zhouping Wang,et al.  Screening and identification of DNA aptamers against T-2 toxin assisted by graphene oxide. , 2014, Journal of agricultural and food chemistry.

[170]  Gerald F. Joyce,et al.  Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA , 1990, Nature.

[171]  Ali Navaei,et al.  PNIPAAm-based biohybrid injectable hydrogel for cardiac tissue engineering. , 2016, Acta biomaterialia.

[172]  Daniel Scherman,et al.  Growth factor delivery approaches in hydrogels. , 2009, Biomacromolecules.

[173]  Andrés J. García,et al.  Bioartificial matrices for therapeutic vascularization , 2009, Proceedings of the National Academy of Sciences.

[174]  D J Mooney,et al.  Alginate hydrogels as synthetic extracellular matrix materials. , 1999, Biomaterials.

[175]  James J. Yoo,et al.  A 3D bioprinting system to produce human-scale tissue constructs with structural integrity , 2016, Nature Biotechnology.

[176]  S. Goldstein,et al.  The elastic moduli of human subchondral, trabecular, and cortical bone tissue and the size-dependency of cortical bone modulus. , 1990, Journal of biomechanics.

[177]  J. Arias Nanotechnology and Drug Delivery, Volume One : Nanoplatforms in Drug Delivery , 2014 .

[178]  C. Werner,et al.  Dual independent delivery of pro-angiogenic growth factors from starPEG-heparin hydrogels. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[179]  Geoffrey L Robb,et al.  Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps. , 2016, Acta Biomaterialia.

[180]  A. Khademhosseini,et al.  Carbon-nanotube-embedded hydrogel sheets for engineering cardiac constructs and bioactuators. , 2013, ACS nano.

[181]  Douglas A Lauffenburger,et al.  Marrow‐Derived stem cell motility in 3D synthetic scaffold is governed by geometry along with adhesivity and stiffness , 2010, Biotechnology and bioengineering.

[182]  Qi Li,et al.  A macroporous hydrogel for the coculture of neural progenitor and endothelial cells to form functional vascular networks in vivo. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[183]  Matthias Wessling,et al.  Gas foaming of segmented poly(ester amide) films , 2005 .