Hydrogels for Engineering of Perfusable Vascular Networks

Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation.

[1]  S. Andreadis,et al.  Engineering of fibrin-based functional and implantable small-diameter blood vessels. , 2005, American journal of physiology. Heart and circulatory physiology.

[2]  Jiandi Wan,et al.  Microfluidic-Based Synthesis of Hydrogel Particles for Cell Microencapsulation and Cell-Based Drug Delivery , 2012 .

[3]  Joe Tien,et al.  Effect of cyclic AMP on barrier function of human lymphatic microvascular tubes. , 2008, Microvascular research.

[4]  Arndt F Schilling,et al.  Mechanical properties of native and tissue-engineered cartilage depend on carrier permeability: a bioreactor study. , 2013, Tissue engineering. Part A.

[5]  Jos Malda,et al.  The roles of hypoxia in the in vitro engineering of tissues. , 2007, Tissue engineering.

[6]  Kemal Arda,et al.  Quantitative assessment of normal soft-tissue elasticity using shear-wave ultrasound elastography. , 2011, AJR. American journal of roentgenology.

[7]  W. Bentley,et al.  Transglutaminase crosslinked gelatin as a tissue engineering scaffold. , 2007, Journal of biomedical materials research. Part A.

[8]  Chaoliang He,et al.  In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[9]  T. Reh,et al.  Guiding the morphogenesis of dissociated newborn mouse retinal cells and hES cell-derived retinal cells by soft lithography-patterned microchannel PLGA scaffolds. , 2012, Biomaterials.

[10]  J. Beamish,et al.  The effects of monoacrylated poly(ethylene glycol) on the properties of poly(ethylene glycol) diacrylate hydrogels used for tissue engineering. , 2009, Journal of biomedical materials research. Part A.

[11]  I. Campbell,et al.  Fibronectin structure and assembly. , 1994, Current opinion in cell biology.

[12]  Feng Xu,et al.  Engineering three-dimensional cell mechanical microenvironment with hydrogels , 2012, Biofabrication.

[13]  D J Beebe,et al.  Gelatin based microfluidic devices for cell culture. , 2006, Lab on a chip.

[14]  Vladimir Mironov,et al.  Organ printing: tissue spheroids as building blocks. , 2009, Biomaterials.

[15]  Michael Simons,et al.  The extracellular matrix and blood vessel formation: not just a scaffold , 2007, Journal of cellular and molecular medicine.

[16]  James G Truslow,et al.  The role of cyclic AMP in normalizing the function of engineered human blood microvessels in microfluidic collagen gels. , 2010, Biomaterials.

[17]  H. Ohgushi,et al.  BMP-induced osteogenesis on the surface of hydroxyapatite with geometrically feasible and nonfeasible structures: topology of osteogenesis. , 1998, Journal of biomedical materials research.

[18]  K. Anseth,et al.  Hydrogel Cell Cultures , 2007, Science.

[19]  Jennifer L West,et al.  Design and characterization of poly(ethylene glycol) photopolymerizable semi-interpenetrating networks for chondrogenesis of human mesenchymal stem cells. , 2007, Tissue engineering.

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

[21]  D. Beebe,et al.  Protocol for the fabrication of enzymatically crosslinked gelatin microchannels for microfluidic cell culture , 2007, Nature Protocols.

[22]  H. Aro,et al.  Pore diameter of more than 100 μm is not requisite for bone ingrowth in rabbits , 2001 .

[23]  Joseph D. Bronzino,et al.  Tissue engineering : principles and practices , 2012 .

[24]  Ali Khademhosseini,et al.  Sequential assembly of cell‐laden hydrogel constructs to engineer vascular‐like microchannels , 2011, Biotechnology and bioengineering.

[25]  Shinji Sakai,et al.  An injectable, in situ enzymatically gellable, gelatin derivative for drug delivery and tissue engineering. , 2009, Biomaterials.

[26]  Ali Khademhosseini,et al.  Fabrication of three-dimensional porous cell-laden hydrogel for tissue engineering , 2010, Biofabrication.

[27]  Ali Khademhosseini,et al.  Progress in tissue engineering. , 2009, Scientific American.

[28]  S. Bryant,et al.  Cell encapsulation in biodegradable hydrogels for tissue engineering applications. , 2008, Tissue engineering. Part B, Reviews.

[29]  Tatsuya Osaki,et al.  Rapid engineering of endothelial cell-lined vascular-like structures in in situ crosslinkable hydrogels , 2014, Biofabrication.

[30]  Pablo Fernandez,et al.  The compaction of gels by cells: a case of collective mechanical activity. , 2009, Integrative biology : quantitative biosciences from nano to macro.

[31]  Glenn D Prestwich,et al.  Modular extracellular matrices: solutions for the puzzle. , 2008, Methods.

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

[33]  F. Nicolas,et al.  Denatured thiolated collagen. I. Synthesis and characterization. , 1997, Biomaterials.

[34]  George M. Whitesides,et al.  Cell Encapsulation in Sub-mm Sized Gel Modules Using Replica Molding , 2008, PloS one.

[35]  L. Shea,et al.  Interpenetrating fibrin-alginate matrices for in vitro ovarian follicle development. , 2009, Biomaterials.

[36]  Yufan Xu,et al.  Fluid and cell behaviors along a 3D printed alginate/gelatin/fibrin channel , 2015, Biotechnology and bioengineering.

[37]  Joe Tien,et al.  Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element. , 2007, Lab on a chip.

[38]  M. Lutolf Biomaterials: Spotlight on hydrogels. , 2009, Nature materials.

[39]  Ying Zheng,et al.  In vitro microvessels for the study of angiogenesis and thrombosis , 2012, Proceedings of the National Academy of Sciences.

[40]  J. Kopeček Hydrogel biomaterials: a smart future? , 2007, Biomaterials.

[41]  F. Nicolas,et al.  Denatured thiolated collagen. II. Cross-linking by oxidation. , 1997, Biomaterials.

[42]  Shuguang Zhang,et al.  Designer self-assembling peptide nanofiber biological materials. , 2010, Chemical Society reviews.

[43]  J. Lewis,et al.  Chaotic mixing in three-dimensional microvascular networks fabricated by direct-write assembly , 2003, Nature materials.

[44]  Luca Gasperini,et al.  Natural polymers for the microencapsulation of cells , 2014, Journal of The Royal Society Interface.

[45]  Junzhu Xiao,et al.  Surface Modification of Poly(dimethylsiloxane) Using Ionic Complementary Peptides to Minimize Nonspecific Protein Adsorption. , 2015, Langmuir : the ACS journal of surfaces and colloids.

[46]  A. Tekinay,et al.  Self-assembled peptide amphiphile nanofibers and peg composite hydrogels as tunable ECM mimetic microenvironment. , 2015, Biomacromolecules.

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

[48]  K. Chennazhi,et al.  Fabrication of poly (L-lactic acid)/gelatin composite tubular scaffolds for vascular tissue engineering. , 2015, International journal of biological macromolecules.

[49]  P. Ma,et al.  Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: part 1. Structure, gelation rate and mechanical properties. , 2001, Biomaterials.

[50]  Alison P McGuigan,et al.  Modular tissue engineering: fabrication of a gelatin‐based construct , 2007, Journal of Tissue Engineering and Regenerative Medicine.

[51]  Joe Tien,et al.  Formation of perfused, functional microvascular tubes in vitro. , 2006, Microvascular research.

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

[53]  Aaron R Wheeler,et al.  A circular cross-section PDMS microfluidics system for replication of cardiovascular flow conditions. , 2010, Biomaterials.

[54]  Eleanor Stride,et al.  Controlled microchannelling in dense collagen scaffolds by soluble phosphate glass fibers. , 2007, Biomacromolecules.

[55]  R. Langer,et al.  Designing materials for biology and medicine , 2004, Nature.

[56]  Ahmad S. Khalil,et al.  Functional endothelialized microvascular networks with circular cross-sections in a tissue culture substrate , 2010, Biomedical microdevices.

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

[58]  Shy Shoham,et al.  Laser photoablation of guidance microchannels into hydrogels directs cell growth in three dimensions. , 2009, Biophysical journal.

[59]  Brahatheeswaran Dhandayuthapani,et al.  Fabrication and characterization of chitosan-gelatin blend nanofibers for skin tissue engineering. , 2010, Journal of biomedical materials research. Part B, Applied biomaterials.

[60]  Glenn D Prestwich,et al.  Bioprinting vessel-like constructs using hyaluronan hydrogels crosslinked with tetrahedral polyethylene glycol tetracrylates. , 2010, Biomaterials.

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

[62]  Alison P McGuigan,et al.  Design and fabrication of sub-mm-sized modules containing encapsulated cells for modular tissue engineering. , 2007, Tissue engineering.

[63]  A. Khademhosseini,et al.  A cell-laden microfluidic hydrogel. , 2007, Lab on a chip.

[64]  Stephanie J Bryant,et al.  Encapsulating chondrocytes in degrading PEG hydrogels with high modulus: Engineering gel structural changes to facilitate cartilaginous tissue production , 2004, Biotechnology and bioengineering.

[65]  M Cornelissen,et al.  Structural and rheological properties of methacrylamide modified gelatin hydrogels. , 2000, Biomacromolecules.

[66]  Ernest S Kim,et al.  A biodegradable microvessel scaffold as a framework to enable vascular support of engineered tissues. , 2013, Biomaterials.

[67]  James G Truslow,et al.  Effect of mechanical factors on the function of engineered human blood microvessels in microfluidic collagen gels. , 2010, Biomaterials.

[68]  Alessandro Tocchio,et al.  Versatile fabrication of vascularizable scaffolds for large tissue engineering in bioreactor. , 2015, Biomaterials.

[69]  Jason A. Burdick,et al.  Hyaluronic Acid Hydrogels for Biomedical Applications , 2011, Advanced materials.

[70]  B. Hinz,et al.  The nano-scale mechanical properties of the extracellular matrix regulate dermal fibroblast function. , 2014, The Journal of investigative dermatology.

[71]  Jason P. Gleghorn,et al.  Microfluidic scaffolds for tissue engineering. , 2007, Nature materials.

[72]  C. Watson,et al.  Collagen-hyaluronic acid scaffolds for adipose tissue engineering. , 2010, Acta biomaterialia.

[73]  Ali Khademhosseini,et al.  Microengineered hydrogels for tissue engineering. , 2007, Biomaterials.

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

[75]  Lauran R. Madden,et al.  Proangiogenic scaffolds as functional templates for cardiac tissue engineering , 2010, Proceedings of the National Academy of Sciences.

[76]  S. Bhatia,et al.  Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[77]  A. Khademhosseini,et al.  Cell-laden microengineered gelatin methacrylate hydrogels. , 2010, Biomaterials.

[78]  J. Hubbell,et al.  Incorporation of adhesion peptides into nonadhesive hydrogels useful for tissue resurfacing. , 1998, Journal of biomedical materials research.

[79]  Yi Yan Yang,et al.  Synthetic hydrogels for controlled stem cell differentiation , 2010 .

[80]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[81]  J. Elisseeff,et al.  Hydrogels for musculoskeletal tissue engineering , 2006 .

[82]  H. Ijima,et al.  Fabrication of endothelialized tube in collagen gel as starting point for self‐developing capillary‐like network to construct three‐dimensional organs in vitro , 2006, Biotechnology and bioengineering.

[83]  Vitoantonio Bevilacqua,et al.  Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering , 2009, BMC Bioinformatics.

[84]  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.

[85]  Robert Langer,et al.  Three‐Dimensional Microfluidic Tissue‐Engineering Scaffolds Using a Flexible Biodegradable Polymer , 2006, Advanced materials.

[86]  Ali Khademhosseini,et al.  Progress in tissue. , 2009 .

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

[88]  In-Yong Kim,et al.  Chitosan and its derivatives for tissue engineering applications. , 2008, Biotechnology advances.

[89]  Feng Xu,et al.  Engineering hydrogels as extracellular matrix mimics. , 2010, Nanomedicine.

[90]  J. Lewis,et al.  Direct-write assembly of biomimetic microvascular networks for efficient fluid transport , 2010 .

[91]  J. Hunt,et al.  Biomimetic materials processing for tissue-engineering processes , 2007 .

[92]  Marcia Simon,et al.  Hydrogels for Regenerative Medicine , 2016 .

[93]  A. Ramamurthi,et al.  Ultraviolet light-induced modification of crosslinked hyaluronan gels. , 2003, Journal of biomedical materials research. Part A.

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

[95]  Alicia C B Allen,et al.  Multilayer microfluidic PEGDA hydrogels. , 2010, Biomaterials.

[96]  G. Prestwich,et al.  Photocrosslinkable hyaluronan-gelatin hydrogels for two-step bioprinting. , 2010, Tissue engineering. Part A.