TY - JOUR
T1 - Autologous minced muscle grafts improve endogenous fracture healing and muscle strength after musculoskeletal trauma
AU - Hurtgen, Brady J.
AU - Ward, Catherine L.
AU - Leopold Wager, Chrissy M.
AU - Garg, Koyal
AU - Goldman, Stephen M.
AU - Henderson, Beth E.P.
AU - McKinley, Todd O.
AU - Greising, Sarah M.
AU - Wenke, Joseph C.
AU - Corona, Benjamin T.
N1 - Publisher Copyright:
© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
KW - Inflammation
KW - insulin-like growth factor-1
KW - orthopedic trauma
KW - regenerative medicine
KW - skeletal muscle injury
KW - volumetric muscle loss
UR - http://www.scopus.com/inward/record.url?scp=85026318293&partnerID=8YFLogxK
U2 - 10.14814/phy2.13362
DO - 10.14814/phy2.13362
M3 - Article
C2 - 28747511
AN - SCOPUS:85026318293
SN - 2051-817X
VL - 5
JO - Physiological Reports
JF - Physiological Reports
IS - 14
M1 - e13362
ER -