The development of glycosaminoglycan-based materials to promote chondrogenic differentiation of mesenchymal stem cells
Lim, Jeremy James
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Tissue engineering strategies represent exciting potential therapies to repair cartilage injuries; however, difficulty regenerating the complex extracellular matrix (ECM) organization of native cartilage remains a significant challenge. Cartilaginous ECM molecules, specifically chondroitin sulfate (CS) glycosaminoglycan, may possess the ability to promote and direct MSC differentiation down a chondrogenic lineage. CS may interact with the stem cell microenvironment through its highly negative charge, generation of osmotic pressure, and sequestration of growth factors; however, the role of CS in directing differentiation down a chondrogenic lineage remains unclear. The overall goal of this dissertation was to develop versatile biomaterial platforms to control CS presentation to mesenchymal stem cells (MSCs) in order to improve understanding of the interactions with CS that promote chondrogenic differentiation. To investigate chondrogenic response to a diverse set of CS materials, progenitor cells were cultured in the presence of CS proteoglycans and CS chains in a variety of 2D and 3D material systems. Surfaces were coated with aggrecan proteoglycan to alter cell morphology, CS-based nano- and microspheres were developed as small particle carriers for growth factor delivery, and desulfated chondroitin hydrogels were synthesized to examine electrostatic interactions with growth factors and the role of sulfation in the chondrogenic differentiation of MSCs. Together these studies provided valuable insight into the unique ability of CS-based materials to control cellular microenvironments via morphological and material cues to promote chondrogenic differentiation in the development of tissue engineering strategies for cartilage regeneration and repair.