Committee Members:
Edward A. Botchwey, PhD (Thesis Advisor)
Andrés J. García, PhD
Young C. Jang, PhD
Gabe A. Kwong, PhD
Gordon L. Warren, PhD

Immunomodulatory Biomaterials for Skeletal Muscle Regeneration

Though skeletal muscle possesses robust potential for healing after injury, large volumetric wounds that occur during combat, accidents or surgical resection often do not heal completely, resulting in fibrotic scarring and limited range of motion. Current standard of care involves the autologous transfer of tissue but exhibits limited success and complications at both the donor and injury site. We have developed strategies that encourage muscle defect healing by recruiting pro-regenerative monocytes to the injured area through local manipulation of microenvironmental cues. The overarching hypothesis of the proposed research is that local activation of sphingosine 1-phosphate receptors within volumetric muscle injury selectively recruits non-classical monocytes from blood to injured muscle where they serve as biased progenitors of wound healing macrophages to promote endogenous repair programs. We will investigate how tuning recruitment of non-classical monocytes impacts wound macrophage accumulation and function within a novel pre-clinical model of volumetric muscle loss in the murine spinotrapezius muscle. We will track interactions of monocytes/macrophages with muscle stem cells via whole-mount immunofluorescence. Restoration of function in regenerated muscle will be assessed using morphological assessments of muscle structure along with contractile force and biochemical measurements.