A porous collagen-GAG scaffold promotes muscle regeneration following volumetric muscle loss injury

Adriana C. Panayi, Lucindi Smit, Nicole Hays, Kodi Udeh, Yori Endo, Bin Li, Dharaniya Sakthivel, Ali Tamayol, Ronald L. Neppl, Dennis P. Orgill, Kristo Nuutila, Indranil Sinha

Research output: Contribution to journalArticle

Abstract

Volumetric muscle loss (VML) is a segmental loss of skeletal muscle which commonly heals with fibrosis, minimal muscle regeneration, and loss of muscle strength. Treatment options for these wounds which promote functional recovery are currently lacking. This study was designed to investigate whether the collagen-GAG scaffold (CGS) promotes functional muscle recovery following VML. A total of 66 C57/Bl6 mice were used in a three-stage experiment. First, 24 animals were split into three groups which underwent sham injury or unilateral quadriceps VML injury with or without CGS implantation. Two weeks post-surgery, muscle was harvested for histological and gene expression analysis. In the second stage, 18 mice underwent bilateral quadriceps VML injury, followed by weekly functional testing using a treadmill. In the third stage, 24 mice underwent sham or bilateral quadriceps VML injury with or without CGS implantation, with tissue harvested six weeks post-surgery for histological and gene expression analysis. VML mice treated with CGS demonstrated increased remnant fiber hypertrophy versus both the VML with no CGS and uninjured groups. Both VML groups showed greater muscle fiber hypertrophy than non-injured muscle. This phenomenon was still evident in the longer-term experiment. The gene array indicated that the CGS promoted upregulation of factors involved in promoting wound healing and regeneration. In terms of functional improvement, the VML mice treated with CGS ran at higher maximum speeds than VML without CGS. A CGS was shown to enhance muscle hypertrophy in response to VML injury with a resultant improvement in functional performance. A gene array highlighted increased gene expression of multiple growth factors following CGS implantation. This suggests that implantation of a CGS could be a promising treatment for VML wounds.

Original languageEnglish (US)
Pages (from-to)61-74
Number of pages14
JournalWound Repair and Regeneration
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2020

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ASJC Scopus subject areas

  • Surgery
  • Dermatology

Cite this

Panayi, A. C., Smit, L., Hays, N., Udeh, K., Endo, Y., Li, B., Sakthivel, D., Tamayol, A., Neppl, R. L., Orgill, D. P., Nuutila, K., & Sinha, I. (2020). A porous collagen-GAG scaffold promotes muscle regeneration following volumetric muscle loss injury. Wound Repair and Regeneration, 28(1), 61-74. https://doi.org/10.1111/wrr.12768