Deconstruction of cellular dynamics after treatment of volumetric muscle loss injury with extracellular matrix
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.
Authors
- Grace E. Kenney (ORCID: https://orcid.org/0000-0002-9579-3351)
- Paula Fraczek (ORCID: https://orcid.org/0000-0002-9897-0720)
- Sandra S. Butler (ORCID: https://orcid.org/0000-0002-0264-5000)
- Bryan N. Brown (ORCID: https://orcid.org/0000-0002-0845-7828)
- Jacqueline Larouche (ORCID: https://orcid.org/0000-0001-9380-3547)
- Carlos A. Aguilar (ORCID: https://orcid.org/0000-0003-3830-0634)
- Clint D. Skillen
- Jiamin Jin (ORCID: https://orcid.org/0000-0003-2725-840X)
- Robert J. Tower (ORCID: https://orcid.org/0000-0001-5856-5758)
- Adrienne A. Giannone (ORCID: https://orcid.org/0000-0002-7177-261X)
- Stephen F. Badylak (ORCID: https://orcid.org/0000-0003-3555-0689)
- Benjamin Levi (ORCID: https://orcid.org/0000-0002-0508-1765)
- Scott A. Johnson (ORCID: https://orcid.org/0000-0002-0164-6802)
- Ponugoti Vasantha Rao (ORCID: https://orcid.org/0000-0001-5470-9785)
- Mangesh M. Kulkarni (ORCID: https://orcid.org/0000-0003-3872-9772)
- Teja Chaparala
Institutions
- University of Pittsburgh (US)
- University of Michigan (US)
- Presbyterian Hospital (US)
- UPMC Presbyterian (US)
- University of Pittsburgh Medical Center (US)
- BioSurfaces (United States) (US)
- McGowan Institute for Regenerative Medicine (US)
- Organogenesis (United States) (US)
Publication Details
- Journal
- npj Regenerative Medicine
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1038/s41536-025-00429-8
- Citations
- 2
- Primary Topic
- Tissue Engineering and Regenerative Medicine
- Type
- article
- Field-Weighted Citation Impact
- 4.01