Hyaluronic Acid Hydrogels for Biomedical Applications

Hyaluronic acid (HA), an immunoneutral polysaccharide that is ubiquitous in the human body, is crucial for many cellular and tissue functions and has been in clinical use for over thirty years. When chemically modified, HA can be transformed into many physical forms-viscoelastic solutions, soft or stiff hydrogels, electrospun fibers, non-woven meshes, macroporous and fibrillar sponges, flexible sheets, and nanoparticulate fluids-for use in a range of preclinical and clinical settings. Many of these forms are derived from the chemical crosslinking of pendant reactive groups by addition/condensation chemistry or by radical polymerization. Clinical products for cell therapy and regenerative medicine require crosslinking chemistry that is compatible with the encapsulation of cells and injection into tissues. Moreover, an injectable clinical biomaterial must meet marketing, regulatory, and financial constraints to provide affordable products that can be approved, deployed to the clinic, and used by physicians. Many HA-derived hydrogels meet these criteria, and can deliver cells and therapeutic agents for tissue repair and regeneration. This progress report covers both basic concepts and recent advances in the development of HA-based hydrogels for biomedical applications.

[1]  Brendon M. Baker,et al.  Fabrication and modeling of dynamic multipolymer nanofibrous scaffolds. , 2009, Journal of biomechanical engineering.

[2]  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.

[3]  Kristi S Anseth,et al.  Three-dimensional growth and function of neural tissue in degradable polyethylene glycol hydrogels. , 2006, Biomaterials.

[4]  M. Horne,et al.  Review Paper: A Review of the Cellular Response on Electrospun Nanofibers for Tissue Engineering , 2009, Journal of biomaterials applications.

[5]  N. Washburn,et al.  Complex fluids based on methacrylated hyaluronic acid. , 2010, Biomacromolecules.

[6]  W. Hennink,et al.  Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the-art and novel application in organ printing. , 2007, Tissue engineering.

[7]  M. Rafailovich,et al.  Traction stresses and translational distortion of the nucleus during fibroblast migration on a physiologically relevant ECM mimic. , 2009, Biophysical journal.

[8]  G. Prestwich,et al.  Effect of Gelatin on Heparin Regulation of Cytokine Release from Hyaluronan-Based Hydrogels , 2008, Drug delivery.

[9]  Christine E Schmidt,et al.  Photopatterned collagen-hyaluronic acid interpenetrating polymer network hydrogels. , 2009, Acta biomaterialia.

[10]  Stephanie J Bryant,et al.  In situ forming degradable networks and their application in tissue engineering and drug delivery. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[11]  G. Prestwich,et al.  Bioreactor-free tissue engineering: directed tissue assembly by centrifugal casting , 2008 .

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

[13]  Lonnie D Shea,et al.  Non-viral vector delivery from PEG-hyaluronic acid hydrogels. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[14]  M. Goligorsky,et al.  Endothelial progenitors encapsulated in bioartificial niches are insulated from systemic cytotoxicity and are angiogenesis competent. , 2010, American journal of physiology. Renal physiology.

[15]  Jason A. Burdick,et al.  Controlling poly(β-amino ester) network properties through macromer branching , 2008 .

[16]  C. Yomota,et al.  Recyclable characteristics of hyaluronate-polyhydroxyethyl acrylate blend hydrogel for controlled releases. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[17]  Jason B. Shear,et al.  High‐Resolution Patterning of Hydrogels in Three Dimensions using Direct‐Write Photofabrication for Cell Guidance , 2009 .

[18]  Xingde Li,et al.  In Situ Characterization of the Degradation of PLGA Microspheres in Hyaluronic Acid Hydrogels by Optical Coherence Tomography , 2009, IEEE Transactions on Medical Imaging.

[19]  Krzysztof Matyjaszewski,et al.  Influence of the degree of methacrylation on hyaluronic acid hydrogels properties. , 2008, Biomaterials.

[20]  J. Burdick,et al.  The influence of degradation characteristics of hyaluronic acid hydrogels on in vitro neocartilage formation by mesenchymal stem cells. , 2009, Biomaterials.

[21]  J. Burdick,et al.  Macromer density influences mesenchymal stem cell chondrogenesis and maturation in photocrosslinked hyaluronic acid hydrogels. , 2009, Osteoarthritis and cartilage.

[22]  Andrew Gouldstone,et al.  Mechanically strong double network photocrosslinked hydrogels from N,N-dimethylacrylamide and glycidyl methacrylated hyaluronan. , 2008, Biomaterials.

[23]  S. Shi,et al.  Tumor-Like Stem Cells Derived from Human Keloid Are Governed by the Inflammatory Niche Driven by IL-17/IL-6 Axis , 2009, PloS one.

[24]  J. Yoon,et al.  Fabrication of Hyaluronic Acid Hydrogel Beads for Cell Encapsulation , 2006, Biotechnology progress.

[25]  G. Prestwich,et al.  Synthetic Extracellular Matrix Enhances Tumor Growth and Metastasis in an Orthotopic Mouse Model of Pancreatic Adenocarcinoma , 2008, Journal of Gastrointestinal Surgery.

[26]  R. Barbucci,et al.  Protein adsorption on derivatives of hyaluronic acid and subsequent cellular response. , 2009, Journal of biomedical materials research. Part A.

[27]  Jason A Burdick,et al.  Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration. , 2009, Tissue engineering. Part B, Reviews.

[28]  E. Caterson,et al.  Human marrow-derived mesenchymal progenitor cells , 2002, Molecular biotechnology.

[29]  Jason A Burdick,et al.  Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. , 2002, Biomaterials.

[30]  T. Park,et al.  Controlled release of plasmid DNA from photo-cross-linked pluronic hydrogels. , 2005, Biomaterials.

[31]  G. Vunjak‐Novakovic,et al.  Engineered microenvironments for controlled stem cell differentiation. , 2009, Tissue engineering. Part A.

[32]  Nicola Elvassore,et al.  Micro-bioreactor array for controlling cellular microenvironments. , 2007, Lab on a chip.

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

[34]  Vladimir Mironov,et al.  Rapid biofabrication of tubular tissue constructs by centrifugal casting in a decellularized natural scaffold with laser-machined micropores , 2009, Journal of materials science. Materials in medicine.

[35]  Glenn D Prestwich,et al.  Synthesis of hyaluronan haloacetates and biology of novel cross-linker-free synthetic extracellular matrix hydrogels. , 2007, Biomacromolecules.

[36]  Glenn D Prestwich,et al.  Tumor engineering: orthotopic cancer models in mice using cell-loaded, injectable, cross-linked hyaluronan-derived hydrogels. , 2007, Tissue engineering.

[37]  Glenn D Prestwich,et al.  Synthesis and characterization of novel thiol-reactive poly(ethylene glycol) cross-linkers for extracellular-matrix-mimetic biomaterials. , 2007, Biomacromolecules.

[38]  G. Prestwich,et al.  Rheological properties of cross-linked hyaluronan-gelatin hydrogels for tissue engineering. , 2009, Macromolecular bioscience.

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

[40]  Robert Langer,et al.  Synthesis and Characterization of in Situ Cross-Linkable Hyaluronic Acid-Based Hydrogels with Potential Application for Vocal Fold Regeneration , 2004 .

[41]  Kristi S. Anseth,et al.  New Directions in Photopolymerizable Biomaterials , 2002 .

[42]  C. Werner,et al.  Matrix elasticity regulates the secretory profile of human bone marrow-derived multipotent mesenchymal stromal cells (MSCs). , 2009, Biochemical and biophysical research communications.

[43]  J. Fraser,et al.  Hyaluronan: its nature, distribution, functions and turnover , 1997, Journal of internal medicine.

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

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

[46]  Vladimir Mironov,et al.  Fabrication of tubular tissue constructs by centrifugal casting of cells suspended in an in situ crosslinkable hyaluronan‐gelatin hydrogel , 2005, Biomaterials.

[47]  G. Prestwich,et al.  Nuclear Magnetic Resonance Metabolomic Footprinting of Human Hepatic Stem Cells and Hepatoblasts Cultured in Hyaluronan‐Matrix Hydrogels , 2008, Stem cells.

[48]  Lori A. Setton,et al.  Photocrosslinkable Hyaluronan as a Scaffold for Articular Cartilage Repair , 2004, Annals of Biomedical Engineering.

[49]  Jason A Burdick,et al.  Review: photopolymerizable and degradable biomaterials for tissue engineering applications. , 2007, Tissue engineering.

[50]  Glenn D Prestwich,et al.  The generation of 3-D tissue models based on hyaluronan hydrogel-coated microcarriers within a rotating wall vessel bioreactor. , 2010, Biomaterials.

[51]  C. Mummery,et al.  Feeder‐Free Monolayer Cultures of Human Embryonic Stem Cells Express an Epithelial Plasma Membrane Protein Profile , 2008, Stem cells.

[52]  Glenn D Prestwich,et al.  Electrospun three-dimensional hyaluronic acid nanofibrous scaffolds. , 2006, Biomaterials.

[53]  Ali Khademhosseini,et al.  Mechanically robust and bioadhesive collagen and photocrosslinkable hyaluronic acid semi-interpenetrating networks. , 2009, Tissue engineering. Part A.

[54]  Glenn D Prestwich,et al.  Engineered extracellular matrices with cleavable crosslinkers for cell expansion and easy cell recovery. , 2008, Biomaterials.

[55]  Jason A Burdick,et al.  Hydrolytically degradable hyaluronic acid hydrogels with controlled temporal structures. , 2008, Biomacromolecules.

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

[57]  Xinqiao Jia,et al.  Structural Analysis and Mechanical Characterization of Hyaluronic Acid-Based Doubly Cross-Linked Networks. , 2009, Macromolecules.

[58]  Darren M Brey,et al.  Electrospinning of photocrosslinked and degradable fibrous scaffolds. , 2008, Journal of biomedical materials research. Part A.

[59]  W McIntosh,et al.  Transdermal photopolymerization for minimally invasive implantation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Christine E Schmidt,et al.  Characterization of protein release from photocrosslinkable hyaluronic acid-polyethylene glycol hydrogel tissue engineering scaffolds. , 2005, Biomaterials.

[61]  A. Khademhosseini,et al.  Microscale technologies for tissue engineering and biology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[62]  Fabio Palumbo,et al.  Disulfide-crosslinked hyaluronan-gelatin hydrogel films: a covalent mimic of the extracellular matrix for in vitro cell growth. , 2003, Biomaterials.

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

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

[65]  Robert Langer,et al.  Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks. , 2005, Biomacromolecules.

[66]  G. Prestwich,et al.  Synthesis and in vitro degradation of new polyvalent hydrazide cross-linked hydrogels of hyaluronic acid. , 1997, Bioconjugate chemistry.

[67]  J. West,et al.  Cell migration through defined, synthetic extracellular matrix analogues , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[68]  Kristyn S Masters,et al.  Crosslinked hyaluronan scaffolds as a biologically active carrier for valvular interstitial cells. , 2005, Biomaterials.

[69]  S. Ishikawa,et al.  Evaluation of in vivo biocompatibility and biodegradation of photocrosslinked hyaluronate hydrogels (HADgels). , 2004, Journal of biomedical materials research. Part A.

[70]  Glenn D Prestwich,et al.  Disulfide cross-linked hyaluronan hydrogels. , 2002, Biomacromolecules.

[71]  J. Burdick,et al.  Influence of three-dimensional hyaluronic acid microenvironments on mesenchymal stem cell chondrogenesis. , 2009, Tissue engineering. Part A.

[72]  M. Grinstaff,et al.  Photocrosslinkable polysaccharides for in situ hydrogel formation. , 2001, Journal of biomedical materials research.

[73]  B. Toole,et al.  Hyaluronan: from extracellular glue to pericellular cue , 2004, Nature Reviews Cancer.

[74]  Jason A. Burdick,et al.  Differential maturation and structure-function relationships in mesenchymal stem cell- and chondrocyte-seeded hydrogels. , 2009, Tissue engineering. Part A.

[75]  Xinqiao Jia,et al.  Perlecan domain I-conjugated, hyaluronic acid-based hydrogel particles for enhanced chondrogenic differentiation via BMP-2 release. , 2009, Biomaterials.

[76]  Richard Heller,et al.  Generation of a tumor spheroid in a microgravity environment as a 3D model of melanoma , 2009, In Vitro Cellular & Developmental Biology - Animal.

[77]  James I. Fells,et al.  Dual activity lysophosphatidic acid receptor pan-antagonist/autotaxin inhibitor reduces breast cancer cell migration in vitro and causes tumor regression in vivo. , 2009, Cancer research.

[78]  R. Lamanna,et al.  Novel hydrogels via click chemistry: synthesis and potential biomedical applications. , 2007, Biomacromolecules.

[79]  S. Carmichael,et al.  Hydrogel Matrix to Support Stem Cell Survival After Brain Transplantation in Stroke , 2010, Neurorehabilitation and neural repair.

[80]  Glenn D Prestwich,et al.  Simplifying the extracellular matrix for 3‐D cell culture and tissue engineering: A pragmatic approach , 2007, Journal of cellular biochemistry.

[81]  Seung Jin Lee,et al.  Electrospinning of polysaccharides for regenerative medicine. , 2009, Advanced drug delivery reviews.

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

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

[84]  G. Prestwich,et al.  Chemically-modified HA for therapy and regenerative medicine. , 2008, Current pharmaceutical biotechnology.

[85]  G. Prestwich,et al.  Dynamically Crosslinked Gold Nanoparticle – Hyaluronan Hydrogels , 2010, Advanced materials.

[86]  Robert Langer,et al.  Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells , 2007, Proceedings of the National Academy of Sciences.

[87]  K. Anseth,et al.  Sequential Click Reactions for Synthesizing and Patterning 3D Cell Microenvironments , 2009, Nature materials.

[88]  Kristi S. Anseth,et al.  The effect of bioactive hydrogels on the secretion of extracellular matrix molecules by valvular interstitial cells. , 2008, Biomaterials.

[89]  L. Álvarez-Vallina,et al.  Tumor Immunotherapy Using Gene-Modified Human Mesenchymal Stem Cells Loaded into Synthetic Extracellular Matrix Scaffolds , 2009, Stem cells.

[90]  B. Toole,et al.  Hyaluronan in morphogenesis. , 2001, Journal of internal medicine.

[91]  Christine E Schmidt,et al.  Development of photocrosslinkable hyaluronic acid-polyethylene glycol-peptide composite hydrogels for soft tissue engineering. , 2004, Journal of biomedical materials research. Part A.

[92]  C. Schmidt,et al.  Photopatterned anisotropic swelling of dual-crosslinked hyaluronic acid hydrogels. , 2009, Acta biomaterialia.

[93]  C. Schmidt,et al.  Crystal templating dendritic pore networks and fibrillar microstructure into hydrogels. , 2010, Acta biomaterialia.

[94]  Differential behavior of auricular and articular chondrocytes in hyaluronic acid hydrogels. , 2008 .

[95]  Ali Khademhosseini,et al.  Micromolding of shape-controlled, harvestable cell-laden hydrogels. , 2006, Biomaterials.

[96]  Robert Langer,et al.  Stimulation of neurite outgrowth by neurotrophins delivered from degradable hydrogels. , 2006, Biomaterials.

[97]  Christine E Schmidt,et al.  Photocrosslinked hyaluronic acid hydrogels: natural, biodegradable tissue engineering scaffolds. , 2003, Biotechnology and bioengineering.

[98]  Vladimir Mironov,et al.  Bioprinting living structures , 2007 .

[99]  Shouren Ge,et al.  Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties. , 2007, Biomaterials.

[100]  Robert Langer,et al.  Micromolding of photocrosslinkable hyaluronic acid for cell encapsulation and entrapment. , 2006, Journal of biomedical materials research. Part A.

[101]  Aniq B. Darr,et al.  Synthesis and characterization of tyramine-based hyaluronan hydrogels , 2009, Journal of materials science. Materials in medicine.

[102]  G. Prestwich,et al.  Stimulation of in vivo angiogenesis by in situ crosslinked, dual growth factor-loaded, glycosaminoglycan hydrogels. , 2010, Biomaterials.

[103]  Jason A Burdick,et al.  Patterning network structure to spatially control cellular remodeling and stem cell fate within 3-dimensional hydrogels. , 2010, Biomaterials.

[104]  Anna Bershteyn,et al.  Bioactive Hydrogels with an Ordered Cellular Structure Combine Interconnected Macroporosity and Robust Mechanical Properties , 2005 .

[105]  Glenn D Prestwich,et al.  Osteochondral defect repair with autologous bone marrow-derived mesenchymal stem cells in an injectable, in situ, cross-linked synthetic extracellular matrix. , 2006, Tissue engineering.

[106]  Dietmar W Hutmacher,et al.  Advanced Tissue Sciences Inc.: learning from the past, a case study for regenerative medicine. , 2010, Regenerative medicine.

[107]  Glenn D Prestwich,et al.  Engineering a clinically-useful matrix for cell therapy , 2008, Organogenesis.

[108]  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.

[109]  Kristyn S Masters,et al.  Designing scaffolds for valvular interstitial cells: cell adhesion and function on naturally derived materials. , 2004, Journal of biomedical materials research. Part A.

[110]  G. Pitarresi,et al.  Photo-cross-linked hydrogels with polysaccharide-poly(amino acid) structure: new biomaterials for pharmaceutical applications. , 2006, Biomacromolecules.

[111]  C. Yeow,et al.  Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells. , 2010, Biomaterials.

[112]  D. Fang,et al.  Electrospinning of Hyaluronic acid (HA) and HA/Gelatin Blends , 2006 .

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

[114]  Terry Kim,et al.  A Photopolymerized Sealant for Corneal Lacerations , 2002, Cornea.

[115]  S. Massia,et al.  Assessment of the cytotoxicity of photocrosslinked dextran and hyaluronan-based hydrogels to vascular smooth muscle cells. , 2002, Biomaterials.

[116]  J. Elisseeff,et al.  Injectable cartilage tissue engineering , 2004, Expert opinion on biological therapy.

[117]  G. Prestwich,et al.  Evaluating dual activity LPA receptor pan-antagonist/autotaxin inhibitors as anti-cancer agents in vivo using engineered human tumors. , 2009, Prostaglandins & other lipid mediators.

[118]  Robert L. Thompson,et al.  Three-dimensional perfusion bioreactor culture supports differentiation of human fetal liver cells. , 2010, Tissue engineering. Part A.

[119]  Jason A. Burdick,et al.  Spatially controlled hydrogel mechanics to modulate stem cell interactions , 2010 .

[120]  G. Prestwich,et al.  Functionalized derivatives of hyaluronic acid oligosaccharides: drug carriers and novel biomaterials. , 1994, Bioconjugate chemistry.

[121]  Glenn D Prestwich,et al.  Synthesis and evaluation of injectable, in situ crosslinkable synthetic extracellular matrices for tissue engineering. , 2006, Journal of biomedical materials research. Part A.

[122]  R. Tuan,et al.  Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy , 2004, Journal of cellular and molecular medicine.

[123]  Glenn D Prestwich,et al.  Evaluating drug efficacy and toxicology in three dimensions: using synthetic extracellular matrices in drug discovery. , 2008, Accounts of chemical research.

[124]  Jason A Burdick,et al.  Influence of gel properties on neocartilage formation by auricular chondrocytes photoencapsulated in hyaluronic acid networks. , 2006, Journal of biomedical materials research. Part A.

[125]  Robert C Gorman,et al.  Injectable hydrogel properties influence infarct expansion and extent of postinfarction left ventricular remodeling in an ovine model , 2010, Proceedings of the National Academy of Sciences.