Oligodendrocyte Progenitor Cells in 3D Hyaluronic Acid Scaffolds

Demyelinating disorders of the central nervous system have few solutions based primarily on immunosuppressive/modulatory therapies. Tissue engineering is known for providing localized treatments where cells in a supporting scaffold can be implanted with the advantage of adaptability to time and space inside the host. In this work, we seek to understand the applications of oligodendrocyte progenitor cells in supporting scaffolds as these may be crucial to understanding complex pathological phenomena associated with this cell type, such as myelination. Chapter 1 focuses on the broad biomaterials applications already developed with these precursor cells and their myelinating differentiated counterparts to elucidate therapies for several disease pathologies. Finding structure property relationships to understand the degree of myelination that occurs as a function of mechanical cues has its challenges, however emerging 3D models are advocated as bridging contributions to the 2D in vitro and in vivo models already devised. Chapter 2 presents the use of oligodendrocyte progenitor cells in hyaluronic acid scaffolds where stiffness in the range of brain tissue is the independent variable and proliferation, metabolic activity, and viability are the dependent variables. This experimentation is important to understand the potential for using hyaluronic acid in this application in comparison to other scaffolding materials. We conclude that the most compliant hydrogels result in the greatest metabolic activity per cell, but all stiffness hydrogels support cells adequately. Once these basic relationships are developed, future work can focus on incorporating axon mimics into these hydrogels and trying to induce myelination to occur starting with process extension to the axon mimics. Hyaluronic acid scaffolds with hyaluronic acid axon mimics have shown promise as a biomaterial combination that promotes oligodendrocyte progenitor cell process extension and increased metabolic activity per cell in comparison to hyaluronic acid without axon mimics.