Engineering Skeletal Muscle with Biodegradable Hydrogels

Harvard University, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): There exists a significant need for skeletal muscle reconstruction or regeneration in a variety of diseases or following trauma, and a new approach to skeletal muscle regeneration is proposed in this application. This approach combines the localized presentation of specific growth factors with cell transplantation using biodegradable polymer vehicles. The vehicles will serve to control the availability of the factors to host and transplanted cells, control the activation and migration of the transplanted cells to repopulate and regenerate damaged host tissue, and regulate muscle vascularization and reinnervation to enhance transplanted and host cell survival. The specific hypothesis guiding this proposal is that the regeneration of damaged muscle tissue can be controlled by providing a sustained delivery of activated satellite cells to the damaged tissue, and regionally regulating VEGF signaling to enhance their survival and participation in regeneration. This hypothesis will be addressed with the following aims: (1) Determine whether sustained delivery of satellite cells leads to repopulation and regeneration of lacerated sternomastoid muscle when delivered using a vehicle designed to activate the cells (e.g., proliferate, migrate) but prevent their terminal differentiation until released. (2) Examine the ability of regionally available vascular endothelial growth factor (VEGF) to promote regeneration of lacerated sternomastoid muscle, and (3) Analyze the regeneration of lacerated sternomastoid muscle following sustained satellite cell delivery using vehicles that provide regional VEGF availability and locally regulate cell activation and migration. The successful completion of these aims will ead to new strategies for the regeneration of functional muscle tissue. This work will likely have significant applications in craniofacial reconstructive surgery, and will apply to the regeneration of muscle throughout the body. In a broader sense, this new approach to tissue regeneration, which focuses on repopulation of damaged tissues by the sustained delivery of cells competent to participate in regeneration in concert with revascularization will likely be broadly applicable to other tissues and organs in the body.