Recent Advances in 3D Tissue Models

Physiologically relevant tissue models that bridge the gap between 2D tissue culture and animal trials would be highly desirable to study the function of tissues in health and disease as well as for the validation of lead compounds during drug development. The field has made impressive advances in 3D culturing cells and organoids in naturally derived materials. Novel, rationally designed, biomimetic materials have been established, which allow the almost individual variation of matrix parameters, such as stiffness, cell adhesion, degradability, or growth factor binding and controlled release. The combination of innovative materials with novel technological platforms such as printing, microfluidics, and additive or preventive manufacturing provides a great potential to build unprecedented, complex tissue models. Here we review recent advances in the design of materials building blocks which allow the formation of 3D structured microenvironments. We will mainly focus on strategies to locally position cell-instructive molecular cues and discuss needs to generate models which would allow the investigator to controllably manipulate cells in their 3D context with the aim to generate complex but yet scalable tissue models.

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

[2]  Huaping Tan,et al.  Alginate-Based Biomaterials for Regenerative Medicine Applications , 2013, Materials.

[3]  Bin Wang,et al.  Human basic fibroblast growth factor fused with Kringle4 peptide binds to a fibrin scaffold and enhances angiogenesis. , 2009, Tissue engineering. Part A.

[4]  Feng Xu,et al.  Three‐Dimensional Magnetic Assembly of Microscale Hydrogels , 2011, Advanced materials.

[5]  Ralph Müller,et al.  Synthetic extracellular matrices for in situ tissue engineering , 2004, Biotechnology and bioengineering.

[6]  Kenneth M. Yamada,et al.  Taking Cell-Matrix Adhesions to the Third Dimension , 2001, Science.

[7]  R. Gelberman,et al.  Controlled-release kinetics and biologic activity of platelet-derived growth factor-BB for use in flexor tendon repair. , 2008, The Journal of hand surgery.

[8]  A A Poot,et al.  Improved endothelialization of vascular grafts by local release of growth factor from heparinized collagen matrices. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[9]  N Pallua,et al.  Modulation of angiogenic potential of collagen matrices by covalent incorporation of heparin and loading with vascular endothelial growth factor. , 2004, Tissue engineering.

[10]  J. Hubbell,et al.  Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[11]  T. Okano,et al.  Cell sheet engineering: a unique nanotechnology for scaffold‐free tissue reconstruction with clinical applications in regenerative medicine , 2010, Journal of internal medicine.

[12]  G. Ellis‐Davies,et al.  Caged compounds: photorelease technology for control of cellular chemistry and physiology , 2007, Nature Methods.

[13]  Georg N Duda,et al.  Biomaterial delivery of morphogens to mimic the natural healing cascade in bone. , 2012, Advanced drug delivery reviews.

[14]  J. Hubbell,et al.  Engineered aprotinin for improved stability of fibrin biomaterials. , 2011, Biomaterials.

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

[16]  Christopher Haslett,et al.  Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: A mechanism for small cell lung cancer growth and drug resistance in vivo , 1999, Nature Medicine.

[17]  Stephen J. Weiss,et al.  Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited , 2009, The Journal of cell biology.

[18]  J. Hubbell,et al.  Neurite extension and in vitro myelination within three-dimensional modified fibrin matrices. , 2005, Journal of neurobiology.

[19]  F A Auger,et al.  A completely biological tissue‐engineered human blood vessel , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  P. Messersmith,et al.  Hydrogels cross-linked by native chemical ligation. , 2009, Biomacromolecules.

[21]  Ursula Graf-Hausner,et al.  Synthetic 3D multicellular systems for drug development. , 2012, Current opinion in biotechnology.

[22]  J. Feijen,et al.  Tissue Regenerating Capacity of Carbodiimide-Crosslinked Dermal Sheep Collagen during Repair of the Abdominal Wall , 1994, The International journal of artificial organs.

[23]  Tze Chiun Lim,et al.  Patterned prevascularised tissue constructs by assembly of polyelectrolyte hydrogel fibres , 2013, Nature Communications.

[24]  Valerie M. Weaver,et al.  The extracellular matrix at a glance , 2010, Journal of Cell Science.

[25]  P. Kincade,et al.  CD44 and its interaction with extracellular matrix. , 1993, Advances in immunology.

[26]  E. Rosenzweig,et al.  Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[27]  Adrian Ranga,et al.  Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix , 2013, Proceedings of the National Academy of Sciences.

[28]  Erkki Ruoslahti,et al.  Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule , 1984, Nature.

[29]  Jason A. Burdick,et al.  Patterning hydrogels in three dimensions towards controlling cellular interactions , 2011 .

[30]  Milica Radisic,et al.  Vascular endothelial growth factor immobilized in collagen scaffold promotes penetration and proliferation of endothelial cells. , 2008, Acta biomaterialia.

[31]  Wendelin Jan Stark,et al.  Crosslinking metal nanoparticles into the polymer backbone of hydrogels enables preparation of soft, magnetic field-driven actuators with muscle-like flexibility. , 2009, Small.

[32]  Jangwook P. Jung,et al.  Multifactorial optimization of endothelial cell growth using modular synthetic extracellular matrices. , 2011, Integrative biology : quantitative biosciences from nano to macro.

[33]  Hideo Namiki,et al.  The effect of micropores in the surface of temperature-responsive culture inserts on the fabrication of transplantable canine oral mucosal epithelial cell sheets. , 2006, Biomaterials.

[34]  Pierre-Alexandre Vidi,et al.  Three-dimensional culture of human breast epithelial cells: the how and the why. , 2013, Methods in molecular biology.

[35]  P. Roughley,et al.  Cartilage proteoglycans: Structure and potential functions , 1994, Microscopy research and technique.

[36]  S. Sakiyama-Elbert,et al.  Fibrin-based tissue engineering scaffolds enhance neural fiber sprouting and delay the accumulation of reactive astrocytes at the lesion in a subacute model of spinal cord injury. , 2010, Journal of biomedical materials research. Part A.

[37]  Robin Shattock,et al.  In Vitro and In Vivo: The Story of Nonoxynol 9 , 2005, Journal of acquired immune deficiency syndromes.

[38]  Martin Ehrbar,et al.  Biomimetic hydrogels for controlled biomolecule delivery to augment bone regeneration. , 2012, Advanced drug delivery reviews.

[39]  J. Hubbell,et al.  Bone healing induced by local delivery of an engineered parathyroid hormone prodrug. , 2009, Biomaterials.

[40]  M. Lutolf,et al.  Patterning of cell-instructive hydrogels by hydrodynamic flow focusing. , 2013, Lab on a chip.

[41]  E. Furst,et al.  Growth factor mediated assembly of cell receptor-responsive hydrogels. , 2007, Journal of the American Chemical Society.

[42]  R. Hynds,et al.  Concise Review: The Relevance of Human Stem Cell‐Derived Organoid Models for Epithelial Translational Medicine , 2013, Stem cells.

[43]  N. Cordes,et al.  Radiobiology goes 3D: how ECM and cell morphology impact on cell survival after irradiation. , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[44]  Glenn D Prestwich,et al.  Injectable glycosaminoglycan hydrogels for controlled release of human basic fibroblast growth factor. , 2005, Biomaterials.

[45]  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.

[46]  S. Koch,et al.  Enhancing angiogenesis in collagen matrices by covalent incorporation of VEGF , 2006, Journal of materials science. Materials in medicine.

[47]  James H Henderson,et al.  Dynamic cell behavior on shape memory polymer substrates. , 2011, Biomaterials.

[48]  J. Feijen,et al.  In vivo recruitment of hematopoietic cells using stromal cell-derived factor 1 alpha-loaded heparinized three-dimensional collagen scaffolds. , 2009, Tissue engineering. Part A.

[49]  Wilfried Weber,et al.  Pharmacologically Controlled Protein Switch for ON-OFF Regulation of Growth Factor Activity , 2013, Scientific Reports.

[50]  Tessa Lühmann,et al.  The induction of cell alignment by covalently immobilized gradients of the 6th Ig-like domain of cell adhesion molecule L1 in 3D-fibrin matrices. , 2009, Biomaterials.

[51]  T. Okano,et al.  Structural characterization of bioengineered human corneal endothelial cell sheets fabricated on temperature-responsive culture dishes. , 2006, Biomaterials.

[52]  Aaron D Baldwin,et al.  Production of heparin-functionalized hydrogels for the development of responsive and controlled growth factor delivery systems. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[53]  Bing Chen,et al.  Improved neovascularization and wound repair by targeting human basic fibroblast growth factor (bFGF) to fibrin , 2008, Journal of Molecular Medicine.

[54]  H. Clevers,et al.  SnapShot: The Intestinal Crypt , 2013, Cell.

[55]  Daniel J. Gould,et al.  Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly(ethylene glycol) hydrogels. , 2011, Acta biomaterialia.

[56]  S. Bryant,et al.  Thermoresponsive, in situ cross-linkable hydrogels based on N-isopropylacrylamide: fabrication, characterization and mesenchymal stem cell encapsulation. , 2011, Acta biomaterialia.

[57]  Ralph Müller,et al.  Engineering the Growth Factor Microenvironment with Fibronectin Domains to Promote Wound and Bone Tissue Healing , 2011, Science Translational Medicine.

[58]  N. Pallua,et al.  Tissue Substitutes with Improved Angiogenic Capabilities: An in vitro Investigation with Endothelial Cells and Endothelial Progenitor Cells , 2009, Cells Tissues Organs.

[59]  W. Murphy,et al.  Modulating growth factor release from hydrogels via a protein conformational change , 2009 .

[60]  Rashid Bashir,et al.  Three-dimensional photopatterning of hydrogels using stereolithography for long-term cell encapsulation. , 2010, Lab on a chip.

[61]  N A Peppas,et al.  Devices based on intelligent biopolymers for oral protein delivery. , 2004, International journal of pharmaceutics.

[62]  M. Goto,et al.  Enzymatic preparation of streptavidin-immobilized hydrogel using a phenolated linear poly(ethylene glycol) , 2013 .

[63]  A A Poot,et al.  Binding and release of basic fibroblast growth factor from heparinized collagen matrices. , 2001, Biomaterials.

[64]  M. Fussenegger,et al.  Synthesis and characterization of PEG-based drug-responsive biohybrid hydrogels. , 2012, Macromolecular rapid communications.

[65]  J. Hubbell,et al.  Heterophilic interactions between cell adhesion molecule L1 and αv β3-integrin induce HUVEC process extension in vitro and angiogenesis in vivo , 2004, Angiogenesis.

[66]  Jennifer L. West,et al.  Tethered-TGF-β increases extracellular matrix production of vascular smooth muscle cells , 2001 .

[67]  G. Prestwich,et al.  Microvascular maturity elicited in tissue treated with cytokine-loaded hyaluronan-based hydrogels. , 2008, Biomaterials.

[68]  Nic D. Leipzig,et al.  Functional immobilization of interferon-gamma induces neuronal differentiation of neural stem cells. , 2009, Journal of biomedical materials research. Part A.

[69]  Maria Karlsson,et al.  A generic strategy for pharmacological caging of growth factors for tissue engineering. , 2013, Chemical communications.

[70]  G. Prestwich,et al.  Stimulation of in vivo angiogenesis using dual growth factor-loaded crosslinked glycosaminoglycan hydrogels. , 2006, Biomaterials.

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

[72]  N. Peppas,et al.  Physicochemical foundations and structural design of hydrogels in medicine and biology. , 2000, Annual review of biomedical engineering.

[73]  P. Friedl,et al.  The Journal of Cell Biology , 2002 .

[74]  Martin Fussenegger,et al.  Scaffold-free cell delivery for use in regenerative medicine. , 2010, Advanced drug delivery reviews.

[75]  S. Sakiyama-Elbert,et al.  Controlled Release of Neurotrophin-3 and Platelet-Derived Growth Factor from Fibrin Scaffolds Containing Neural Progenitor Cells Enhances Survival and Differentiation into Neurons in a Subacute Model of SCI , 2010, Cell transplantation.

[76]  Adrian Ranga,et al.  Engineering 3D cell instructive microenvironments by rational assembly of artificial extracellular matrices and cell patterning. , 2011, Integrative biology : quantitative biosciences from nano to macro.

[77]  Lucie Germain,et al.  Tissue-engineered vascular adventitia with vasa vasorum improves graft integration and vascularization through inosculation. , 2010, Tissue engineering. Part A.

[78]  Zhifeng Xiao,et al.  Collagen membranes loaded with collagen-binding human PDGF-BB accelerate wound healing in a rabbit dermal ischemic ulcer model , 2007, Growth factors.

[79]  Jason A. Burdick,et al.  Sequential crosslinking to control cellular spreading in 3-dimensional hydrogels , 2009 .

[80]  Allan S Hoffman,et al.  Injectable pH- and temperature-responsive poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers for delivery of angiogenic growth factors. , 2010, Biomacromolecules.

[81]  Giovanny F. Acosta-Vélez,et al.  Hybrid Photopatterned Enzymatic Reaction (HyPER) for in Situ Cell Manipulation , 2014, Chembiochem : a European journal of chemical biology.

[82]  Christopher S. Chen,et al.  Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. , 2004, Developmental cell.

[83]  Jean Dubé,et al.  A novel single-step self-assembly approach for the fabrication of tissue-engineered vascular constructs. , 2010, Tissue engineering. Part A.

[84]  Zhifeng Xiao,et al.  Linear ordered collagen scaffolds loaded with collagen-binding brain-derived neurotrophic factor improve the recovery of spinal cord injury in rats. , 2009, Tissue engineering. Part A.

[85]  W. Weber,et al.  Pharmacologically tunable polyethylene-glycol-based cell growth substrate. , 2013, Acta biomaterialia.

[86]  A. Metters,et al.  Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: Engineering cell-invasion characteristics , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[87]  J. Hubbell,et al.  Engineered fibrin matrices for functional display of cell membrane-bound growth factor-like activities: study of angiogenic signaling by ephrin-B2. , 2004, Biomaterials.

[88]  Laura J Suggs,et al.  Controlled release of stromal cell-derived factor-1 alpha in situ increases c-kit+ cell homing to the infarcted heart. , 2007, Tissue engineering.

[89]  C. Werner,et al.  Defined Polymer–Peptide Conjugates to Form Cell‐Instructive starPEG–Heparin Matrices In Situ , 2013, Advanced materials.

[90]  Kwideok Park,et al.  Chondrocyte 3D-culture in RGD-modified crosslinked hydrogel with temperature-controllable modulus , 2011, Macromolecular Research.

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

[92]  J. Feijen,et al.  In vivo biocompatibility of carbodiimide-crosslinked collagen matrices: Effects of crosslink density, heparin immobilization, and bFGF loading. , 2001, Journal of biomedical materials research.

[93]  Robert Langer,et al.  Principles of tissue engineering , 2014 .

[94]  D Seliktar,et al.  MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing. , 2004, Journal of biomedical materials research. Part A.

[95]  J. Feijen,et al.  Endothelial cell seeding of (heparinized) collagen matrices: effects of bFGF pre-loading on proliferation (after low density seeding) and pro-coagulant factors. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[96]  Hanna M. Wischhusen,et al.  A Versatile Approach to Engineering Biomolecule‐Presenting Cellular Microenvironments , 2013, Advanced healthcare materials.

[97]  Mikaël M. Martino,et al.  Growth Factors Engineered for Super-Affinity to the Extracellular Matrix Enhance Tissue Healing , 2014, Science.

[98]  J. Vörös,et al.  Electrochemical Control of the Enzymatic Polymerization of PEG Hydrogels: Formation of Spatially Controlled Biological Microenvironments , 2014, Advanced healthcare materials.

[99]  Fan Yang,et al.  Engineering interpenetrating network hydrogels as biomimetic cell niche with independently tunable biochemical and mechanical properties. , 2014, Biomaterials.

[100]  Sangeeta N Bhatia,et al.  Multiplexed, high-throughput analysis of 3D microtissue suspensions. , 2010, Integrative biology : quantitative biosciences from nano to macro.

[101]  J. Hubbell,et al.  The role of actively released fibrin-conjugated VEGF for VEGF receptor 2 gene activation and the enhancement of angiogenesis. , 2008, Biomaterials.

[102]  J. Hubbell,et al.  SPARC-derived protease substrates to enhance the plasmin sensitivity of molecularly engineered PEG hydrogels. , 2011, Biomaterials.

[103]  Franz E Weber,et al.  Bone repair with a form of BMP-2 engineered for incorporation into fibrin cell ingrowth matrices. , 2005, Biotechnology and bioengineering.

[104]  A. Hoffman,et al.  Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH , 1995, Nature.

[105]  Kristi S Anseth,et al.  Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. , 2009, Biomaterials.

[106]  J. Hubbell,et al.  Development of fibrin derivatives for controlled release of heparin-binding growth factors. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

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

[108]  K. J. Grande-Allen,et al.  Review. Hyaluronan: a powerful tissue engineering tool. , 2006, Tissue engineering.

[109]  D. Eberli,et al.  Long-term biostability and bioactivity of "fibrin linked" VEGF121in vitro and in vivo. , 2014, Biomaterials science.

[110]  Kristi S. Anseth,et al.  Photodegradable Hydrogels for Dynamic Tuning of Physical and Chemical Properties , 2009, Science.

[111]  D. Schmaljohann Thermo- and pH-responsive polymers in drug delivery. , 2006, Advanced drug delivery reviews.

[112]  Janos Vörös,et al.  pH-controlled recovery of placenta-derived mesenchymal stem cell sheets. , 2011, Biomaterials.

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

[114]  Samuel K Sia,et al.  Direct patterning of composite biocompatible microstructures using microfluidics. , 2007, Lab on a chip.

[115]  Glenn D Prestwich,et al.  Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing , 2007, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[116]  S. Sakiyama-Elbert,et al.  Effect of controlled delivery of neurotrophin-3 from fibrin on spinal cord injury in a long term model. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[117]  Marcin Maruszewski,et al.  Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study , 2009, The Lancet.

[118]  Zhifeng Xiao,et al.  Collagen-binding human epidermal growth factor promotes cellularization of collagen scaffolds. , 2009, Tissue engineering. Part A.

[119]  Jeffrey A. Hubbell,et al.  Cell-Demanded Liberation of VEGF121 From Fibrin Implants Induces Local and Controlled Blood Vessel Growth , 2004, Circulation research.

[120]  J. Mcdonald,et al.  Controlled release of neurotrophin-3 from fibrin gels for spinal cord injury. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

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

[122]  J. Mano,et al.  Development of bioactive and biodegradable chitosan-based injectable systems containing bioactive glass nanoparticles. , 2009, Acta biomaterialia.

[123]  H. Bentz,et al.  Improved local delivery of TGF-beta2 by binding to injectable fibrillar collagen via difunctional polyethylene glycol. , 1998, Journal of biomedical materials research.

[124]  Kristi S Anseth,et al.  Photoreversible Patterning of Biomolecules within Click-Based Hydrogels , 2011, Angewandte Chemie.

[125]  G. Prestwich,et al.  Recruitment of endogenous stem cells for tissue repair. , 2008, Macromolecular bioscience.

[126]  Kenneth M. Yamada,et al.  Modeling Tissue Morphogenesis and Cancer in 3D , 2007, Cell.

[127]  Matthias P Lutolf,et al.  Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering. , 2007, Biomaterials.

[128]  M. Meuli,et al.  Modified plastic compression of collagen hydrogels provides an ideal matrix for clinically applicable skin substitutes. , 2012, Tissue engineering. Part C, Methods.

[129]  Kristi L Kiick,et al.  Manipulation of hydrogel assembly and growth factor delivery via the use of peptide-polysaccharide interactions. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[130]  Wolfgang Moritz,et al.  Towards automated production and drug sensitivity testing using scaffold-free spherical tumor microtissues. , 2011, Biotechnology journal.

[131]  F. Veronese Peptide and protein PEGylation: a review of problems and solutions. , 2001, Biomaterials.

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

[133]  C. Wise Epithelial cell culture protocols , 2002 .

[134]  J. Hubbell,et al.  Incorporation of heparin‐binding peptides into fibrin gels enhances neurite extension: an example of designer matrices in tissue engineering , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[135]  Sung Hye Kim,et al.  Cell-mediated Delivery and Targeted Erosion of Vascular Endothelial Growth Factor-Crosslinked Hydrogels. , 2010, Macromolecular rapid communications.

[136]  Robert J Fisher,et al.  Heparin-regulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF. , 2006, Biomaterials.

[137]  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.

[138]  Mitsuo Umezu,et al.  In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels , 2013, Nature Communications.

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

[140]  M. Fussenegger,et al.  Drug-sensing hydrogels for the inducible release of biopharmaceuticals. , 2008, Nature materials.

[141]  J. Hubbell,et al.  Development of growth factor fusion proteins for cell‐triggered drug delivery , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[142]  H. Clevers,et al.  Single Lgr5 stem cells build crypt–villus structures in vitro without a mesenchymal niche , 2009, Nature.

[143]  P. Friedl,et al.  The biology of cell locomotion within three-dimensional extracellular matrix , 2000, Cellular and Molecular Life Sciences CMLS.

[144]  G. Skjåk-Bræk,et al.  Alginate as immobilization matrix for cells. , 1990, Trends in biotechnology.

[145]  Brendon M. Baker,et al.  Rapid casting of patterned vascular networks for perfusable engineered 3D tissues , 2012, Nature materials.

[146]  Matthias P Lutolf,et al.  Biomolecular hydrogels formed and degraded via site-specific enzymatic reactions. , 2007, Biomacromolecules.

[147]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[148]  L. Griffith,et al.  Capturing complex 3D tissue physiology in vitro , 2006, Nature Reviews Molecular Cell Biology.

[149]  Samuel K Sia,et al.  Assembly of complex cell microenvironments using geometrically docked hydrogel shapes , 2013, Proceedings of the National Academy of Sciences.

[150]  Buddy D. Ratner,et al.  Biomaterials Science: An Introduction to Materials in Medicine , 1996 .

[151]  KR Stevens,et al.  InVERT molding for scalable control of tissue microarchitecture , 2013, Nature Communications.

[152]  E. Jabbari,et al.  Effect of grafting RGD and BMP-2 protein-derived peptides to a hydrogel substrate on osteogenic differentiation of marrow stromal cells. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[153]  H. Kleinman,et al.  Matrigel: basement membrane matrix with biological activity. , 2005, Seminars in cancer biology.

[154]  M. Fussenegger,et al.  Effects of Protein and Gene Transfer of the Angiopoietin-1 Fibrinogen-like Receptor-binding Domain on Endothelial and Vessel Organization* , 2005, Journal of Biological Chemistry.

[155]  Masayuki Yamato,et al.  Fabrication of transferable micropatterned-co-cultured cell sheets with microcontact printing. , 2009, Biomaterials.

[156]  Mikaël M. Martino,et al.  The 12th-14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain. , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

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

[158]  Matthias P Lutolf,et al.  The effect of matrix characteristics on fibroblast proliferation in 3D gels. , 2010, Biomaterials.

[159]  A. Khademhosseini,et al.  Micro‐Masonry: Construction of 3D Structures by Microscale Self‐Assembly , 2010, Advanced materials.

[160]  Hyoungshin Park,et al.  Mechanical properties and remodeling of hybrid cardiac constructs made from heart cells, fibrin, and biodegradable, elastomeric knitted fabric. , 2005, Tissue engineering.

[161]  R. Shah,et al.  Supramolecular design of self-assembling nanofibers for cartilage regeneration , 2010, Proceedings of the National Academy of Sciences of the United States of America.

[162]  S J Bryant,et al.  Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro , 2000, Journal of biomaterials science. Polymer edition.

[163]  K. Anseth,et al.  Heparin functionalized PEG gels that modulate protein adsorption for hMSC adhesion and differentiation. , 2005, Acta biomaterialia.

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

[165]  Kristi S Anseth,et al.  Controlling Affinity Binding with Peptide‐Functionalized Poly(ethylene glycol) Hydrogels , 2009, Advanced functional materials.

[166]  K. Hasegawa,et al.  In situ cross-linkable hydrogel of hyaluronan produced via copper-free click chemistry. , 2013, Biomacromolecules.

[167]  Lucie Germain,et al.  Human fibroblast-derived ECM as a scaffold for vascular tissue engineering. , 2012, Biomaterials.

[168]  J. Hubbell,et al.  Covalently conjugated VEGF--fibrin matrices for endothelialization. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[169]  Zev J Gartner,et al.  Directing the assembly of spatially organized multicomponent tissues from the bottom up. , 2012, Trends in cell biology.

[170]  Matthew J. Silva,et al.  PDGF‐BB released in tendon repair using a novel delivery system promotes cell proliferation and collagen remodeling , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[171]  Daniel J. Gould,et al.  Biomimetic hydrogels with immobilized ephrinA1 for therapeutic angiogenesis. , 2011, Biomacromolecules.

[172]  G. Prestwich,et al.  Controlled chemical modification of hyaluronic acid: synthesis, applications, and biodegradation of hydrazide derivatives. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[173]  Kristi S. Anseth,et al.  Peptide-Functionalized Click Hydrogels with Independently Tunable Mechanics and Chemical Functionality for 3D Cell Culture , 2010, Chemistry of materials : a publication of the American Chemical Society.

[174]  J. Hubbell,et al.  Engineered insulin-like growth factor-1 for improved smooth muscle regeneration. , 2012, Biomaterials.

[175]  S. Andreadis,et al.  Biomimetic delivery of keratinocyte growth factor upon cellular demand for accelerated wound healing in vitro and in vivo. , 2005, The American journal of pathology.

[176]  P. Keng,et al.  Enhancement of radiosensitivity in H1299 cancer cells by actin-associated protein cofilin. , 2005, Biochemical and biophysical research communications.

[177]  Martin Fussenegger,et al.  Tissue-transplant fusion and vascularization of myocardial microtissues and macrotissues implanted into chicken embryos and rats. , 2006, Tissue engineering.

[178]  Martin Ehrbar,et al.  Endothelial cell proliferation and progenitor maturation by fibrin-bound VEGF variants with differential susceptibilities to local cellular activity. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

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

[180]  N Pallua,et al.  Effects of Modified Collagen Matrices on Human Umbilical Vein Endothelial Cells , 2005, The International journal of artificial organs.