Volumetric muscle loss (VML) injuries present chronic loss of muscle fibers followed by expansive fibrotic tissue deposition. Regenerative medicine therapies are under development to promote regeneration. However, mitigation of the expansive fibrous tissue is required for integration with the remaining muscle. Using a porcine VML model, delayed debridement of injury fibrosis was performed 3 months post-VML and observed for an additional 4 weeks. A second group underwent the initial VML and was observed for 4 weeks, allowing comparison of initial fibrosis formation and debrided groups. The following salient observations were made: (i) debridement neither exacerbated nor ameliorated strength deficits; (ii) debridement results in recurrent fibrotic tissue deposition of a similar magnitude and composition as acute VML injury; and (iii) similarly upregulated transcriptional fibrotic and transcriptional pathways persist 4 weeks after initial VML or delayed debridement. This highlights the need for future studies to investigate adjunctive antifibrotic treatments for the fibrosed musculature.
Bibliographical noteFunding Information:
We gratefully acknowledge the USAISR Veterinary Support and Comparative Pathology Branches, Monica Jalomo, and Javier Chapa for technical assistance in the completion of these studies. Studies were funded through the Congressionally Directed Medical Research Program (Award #MR140099 awarded to B.T.C.). The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army, the Department of Defense, or the United States Government. B.T.C. and S.M.G. wrote the manuscript. B.T.C. and S.M.G. designed the research. B.T.C., J.C.R., and S.M.G. performed the research. B.T.C. and S.M.G. analyzed the data.
Source of Funding. Studies were funded through the Congressionally Directed Medical Research Program (Award #MR140099 awarded to B.T.C.).
© 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics
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