The development of glycosaminoglycan coatings for mesenchymal stem cell-based culture applications
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Mesenchymal stem cells are multipotent cells that have the ability to differentiate down multiple lineages as well as secrete trophic and anti-inflammatory factors. These qualities make MSCs a promising cell source for cell-based therapies to treat a variety of injuries and pathologies. Biomaterials are often used to control and direct stem cell behavior by engineering a desired environment around the cells. Recent research has focused on using the naturally derived sulfated glycosaminoglycan (GAG), heparin as a biomaterial due to its negative charge and ability to sequester and bind positively charged growth factors. Engineering a heparin coating that can mimic the native heparan sulfate proteoglycan structure found at cell surfaces can be used as a novel platform to present GAGs to cells to direct cell behavior. The overall goal of this dissertation was to develop GAG-based coatings on MSC spheroids in order to study the role of heparin and its derivatives on MSC culture applications. To investigate the role of heparin in coating form on MSC behavior, the ability of the coating to sequester positively charged growth factors was characterized. Given the role of sulfation in the negative charge density of heparin and growth factor interactions, a desulfated heparin coating was develop and used to examine how presentation of coatings with native and no sulfation levels could potentiate response to growth factors in the surrounding environment. Additionally, heparin and growth factor binding in coating presentation was explored to develop a novel platform to assemble MSC-based microtissues. Together these studies provided valuable insight into a novel approach to direct cell behavior by engineering a coating that harnesses heparin interactions with the surrounding environment.