Tolerized Dendritic Cells Delivered via PEG-4MAL Hydrogels for Amelioration of Multiple Sclerosis
Multiple Sclerosis (MS) is an autoimmune disease that causes neurodegeneration and destruction of myelin in the CNS, resulting in physical and cognitive impairments. Currently there is no cure for MS and present treatment strategies can only slow disease progression and come with a myriad of complicated side effects. The purpose of this project is to (1) elucidate structure-function relationships between PEG-4MAL scaffolds and encapsulated dendritic cells (DCs), (2) incorporate adhesive and immunological cues to promote sustained function of tolerogenic DCs post-injection, and (3) evaluate the efficacy of hydrogel-delivered tolerogenic DCs to ameliorate autoimmune disease in a murine model of MS. Work outlined herein will uncover previously uncharacterized relationships between mechanical and adhesive properties of matrices on DC tolerogenicity for informed design of biomaterial delivery strategies. Proposed work will also provide a proof-of-concept treatment strategy for antigen-specific, DC-mediated treatment of MS. Immunological studies are expected to illustrate underlying mechanisms of amelioration and provide insight for further development of treatment strategies against autoimmunity.