Date of Graduation

12-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Engineering (PhD)

Degree Level

Graduate

Department

Biomedical Engineering

Advisor/Mentor

Jeffrey Wolchok

Committee Member

Timothy Muldoon

Second Committee Member

Tyrone Washington

Third Committee Member

Morten Jensen

Keywords

Applied sciences, Fibrosis, Muscle volume, Skeletal muscle repair

Abstract

Volumetric muscle loss (VML) is an injury to skeletal muscle characterized by a loss of more than 20% of a muscles volume. The combination of the bulk loss of tissue, transection and separation of myofibers proximal and distal to the injury, loss of innervation and blood supply, and the depletion of muscle progenitor cells results in permanent fibrosis and functional deficits due to loss of contractile tissue. Scaffolds, cells, and engineered constructs have been explored as potential therapeutic interventions to induce myogenesis at the site of a VML injury in animal models, in addition to limited clinical trials. This dissertation summarizes the current state of the field and explores possible strategies for repairing VML and understanding the mechanisms underlying the regenerative response of VML-damaged muscle. The challenges currently facing the skeletal muscle tissue engineering are presented along with potential approaches to further the field and deliver effective treatment options for patients and their physicians.

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