Delivery of Immunomodulatory Microparticles in a Murine Model of Rotator Cuff Tear.

Full thickness rotator cuff tears (RCT) and the associated muscle degeneration that results due to this injury presents a significant clinical burden. The prevention or recovery from this degeneration requires the synchronized behavior of many cells that participate in regeneration. Strategies that tune the inflammatory cascade that is initiated after injury serves as a powerful way to influence tissue repair. Here, we use the local, sustained delivery of the immunomodulatory small molecule FTY720 to examine whether the recruitment of pro-regenerative myeloid cells affects the healing outcome. We find that PLGA microparticles have an atrophic effect on the muscle that is ameliorated with the release of FTY720. However, the inability of FTY720 delivery to induce pro-regenerative monocyte and macrophage recruitment and our findings demonstrating enrichment of CD4+ T cells suggest that effects of this small molecule are context dependent and that the underlying mechanisms behind this RCT associated muscle degeneration require further studies.