Autologous minced muscle grafts improve endogenous fracture healing and muscle strength after musculoskeletal trauma

Brady J. Hurtgen, Catherine L. Ward, Chrissy M. Leopold Wager, Koyal Garg, Stephen M. Goldman, Beth E.P. Henderson, Todd O. McKinley, Sarah M. Greising, Joseph C. Wenke, Benjamin T. Corona*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


The deleterious impact of concomitant muscle injury on fracture healing and limb function is commonly considered part of the natural sequela of orthopedic trauma. Recent reports suggest that heightened inflammation in the surrounding traumatized musculature is a primary determinant of fracture healing. Relatedly, there are emerging potential therapeutic approaches for severe muscle trauma (e.g., volumetric muscle loss [VML] injury), such as autologous minced muscle grafts (1 mm3 pieces of muscle; GRAFT), that can partially prevent chronic functional deficits and appear to have an immunomodulatory effect within VML injured muscle. The primary goal of this study was to determine if repair of VML injury with GRAFT rescues impaired fracture healing and improves the strength of the traumatized muscle in a male Lewis rat model of tibia open fracture. The most salient findings of the study were: (1) tibialis anterior (TA) muscle repair with GRAFT improved endogenous healing of fractured tibia and improved the functional outcome of muscle regeneration; (2) GRAFT repair attenuated the monocyte/macrophage (CD45+CDllb+) and T lymphocyte (CD3+) response to VML injury; (3) TA muscle protein concentrations of MCP1, IL-10, and IGF-1 were augmented in a proregenerative manner by GRAFT repair; (4) VML injury concomitant with osteotomy induced a heightened systemic presence of alarmins (e.g., soluble RAGE) and leukocytes (e.g., monocytes), and depressed IGF-1 concentration, which GRAFT repair ameliorated. Collectively, these data indicate that repair of VML injury with a regenerative therapy can modulate the inflammatory and regenerative phenotype of the treated muscle and in association improve musculoskeletal healing.

Original languageEnglish
Article numbere13362
JournalPhysiological Reports
Issue number14
StatePublished - Jul 2017
Externally publishedYes


  • Inflammation
  • insulin-like growth factor-1
  • orthopedic trauma
  • regenerative medicine
  • skeletal muscle injury
  • volumetric muscle loss


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