| Following trauma from high-energy blasts, a population of multipotent progenitor cells (MPCs) can be derived from the debrided muscle tissue. Given the non-intrusive nature of MPC isolation, MPCs represent an attractive clinical alternative to the more widely used mesenchymal stem cells derived from bone marrow and other tissue sources. This dissertation presents work which further defines the utility and limitations of MPCs in applications relevant to the repair of extremity injuries, including angiogenesis, peripheral nerve repair, and bone formation.;Neurotrophically-induced MPCs, in combination with endothelial cells (ECs) co-cultured on aligned, nanofibrous scaffolds or via secretome interactions, supported neurite outgrowth and extension of chick embryonic dorsal root ganglia. These findings suggest that products of induced MPCs may be useful to enhance nerve guide conduit-based repair of peripheral nerves.;ECs influenced earlier and stronger MPC osteogenic gene expression, and IL-1â was associated with increased mineralization. The use of MPCs in bone replacement applications may thus result in mineralization without functional bone formation, depending on the level of inflammation at the site of construct implantation.;Taken together, this work extends the potential utility of MPCs for limb regenerative applications, especially for enhanced vessel or nerve recruitment. Caution must be exercised as MPCs may be influenced towards a mineralizing phenotype by the tissue environment, likely contributing to the heterotopic ossification pathology commonly seen following blast trauma.;The secretome of MPCs enhanced in vitro angiogenesis, in a manner dependent on MPC production of vascular endothelial growth factor-A (VEGF). Encapsulated within mechanically tunable injectable hydrogel constructs, MPCs retained strong pro-angiogenic activity when implanted in vivo, supporting potential clinical use when enhanced vessel recruitment is desired. |
