title: Hydrolytically degradable hyaluronic acid hydrogels with controlled temporal structures.
abstract: Polysaccharides are being processed into biomaterials for numerous biological applications due to their native source in numerous tissues and biological functions. For instance, hyaluronic acid (HA) is found abundantly in the body, interacts with cells through surface receptors, and can regulate cellular behavior (e.g., proliferation, migration). HA was previously modified with reactive groups to form hydrogels that are degraded by hyaluronidases, either added exogenously or produced by cells. However, these hydrogels may be inhibitory and their applications are limited if the appropriate enzymes are not present. Here, for the first time, we synthesized HA macromers and hydrogels that are both hydrolytically (via ester group hydrolysis) and enzymatically degradable. The hydrogel degradation and growth factor release was tailored through the hydrogel cross-linking density (i.e., macromer concentration) and copolymerization with purely enzymatically degradable macromers. When mesenchymal stem cells (MSCs) were encapsulated in the hydrogels, cellular organization and tissue distribution was influenced by the copolymer concentration. Importantly, the distribution of released extracellular matrix molecules (e.g., chondroitin sulfate) was improved with increasing amounts of the hydrolytically degradable component. Overall, this new macromer allows for enhanced control over the structural evolution of the HA hydrogels toward applications as biomaterials.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Sujata
authors.initials: S
authors.lastname: Sahoo
authors.forename: Cindy
authors.initials: C
authors.lastname: Chung
authors.forename: Sudhir
authors.initials: S
authors.lastname: Khetan
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D001853:Bone Marrow / Q000378:metabolism; D002470:Cell Survival; D002809:Chondroitin Sulfates / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004952:Esters / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006821:Hyaluronoglucosaminidase; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D007124:Immunoenzyme Techniques; D009682:Magnetic Resonance Spectroscopy; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004952:Esters; D020100:Hydrogels; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D006821:Hyaluronoglucosaminidase