Deconstruction of cellular dynamics after treatment of volumetric muscle loss injury with extracellular matrix
Year: 2025
Type: article
Abstract: The acute loss of critical skeletal muscle volume or volumetric muscle loss (VML) results in persistent inflammation, fibrotic scarring, permanent strength deficits and long-term disability. The molecular mechanisms that drive fibrosis following VML injury have primarily been evaluated in rodent models, however, translation of these findings to large animals remains underexplored. Herein, we utilized a canine model of VML and a mesoscopic approach to evaluate how treatment with an extracellular matrix hydrogel impacts the early cellular circuitry regulating inflammation, fibrosis and muscle regeneration. We observed treatment with extracellular matrix dampens inflammation and fibrosis by spatially confining the immune reaction to the superficial surface of the wound. Simultaneously, extracellular matrix treatment improved muscle stem cell and regenerative progenitor infiltration into the VML defect and limited degeneration of intact myofibers. These results establish a spatially informed framework for understanding how extracellular matrix hydrogel treatment impacts regenerative trajectories and cellular communities post-VML.
Source: npj Regenerative Medicine
Authors: Adrienne A. Giannone, Shanae A.-M. Butler, Jacqueline A. Larouche, Paula M. Fraczek, Grace Kenney, Scott A. Johnson, Clint D. Skillen, Pranav Rao, Jessie Jin, Teja Chaparala, Mangesh Kulkarni, Robert J. Tower, Benjamin Levi, Stephen F. Badylak, Bryan N. Brown, Carlos A. Aguilar
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: Hevolution Foundation, National Science Foundation, U.S. Department of Defense, U.S. Department of the Interior, National Institutes of Health, Directorate for Engineering, Defense Advanced Research Projects Agency, Genentech, Horace H. Rackham School of Graduate Studies, University of Michigan, Advanced Research Projects Agency, Interior Business Center, Congressionally Directed Medical Research Programs, Biological Technologies Office
Awards: G2101069996, G2252481087, G2357065241, G4166482221, G4678855261, Immunotargeting and Metabolic Therapeutic Strategies to Improve Muscle Recovery After Severe Trauma, G51574577, G5212437691, G6671297155, Graduate Research Fellowship Program (GRFP), CAREER: Understanding the Interdependence of the Microenvironment and Nuclear Organization in Stem Cell Aging, G7677753315, Graduate Research Fellowship Program (GRFP), G9000024900, G9000270865
OpenAlex ID: W4414601760