title: Autologous minced muscle grafts: a tissue engineering therapy for the volumetric loss of skeletal muscle.
abstract: Volumetric muscle loss (VML) results in a large void deficient in the requisite materials for regeneration for which there is no definitive clinical standard of care. Autologous minced muscle grafts (MG), which contain the essential components for muscle regeneration, may embody an ideal tissue engineering therapy for VML. The purpose of this study was to determine if orthotopic transplantation of MG acutely after VML in the tibialis anterior muscle of male Lewis rats promotes functional tissue regeneration. Herein we report that over the first 16 wk postinjury, MG transplantation 1) promotes remarkable regeneration of innervated muscle fibers within the defect area (i.e., de novo muscle fiber regeneration); 2) reduced evidence of chronic injury in the remaining muscle mass compared with nonrepaired muscles following VML (i.e., transplantation attenuated chronically upregulated transforming growth factor-β1 gene expression and the presence of centrally located nuclei in 30% of fibers observed in nonrepaired muscles); and 3) significantly improves net torque production (i.e., ∼55% of the functional deficit in nonrepaired muscles was restored). Additionally, voluntary wheel running was shown to reduce the heightened accumulation of extracellular matrix deposition observed within the regenerated tissue of MG-repaired sedentary rats 8 wk postinjury (collagen 1% area: sedentary vs. runner, ∼41 vs. 30%), which may have been the result of an augmented inflammatory response [i.e., M1 (CCR7) and M2 (CD163) macrophage expression was significantly greater in runner than sedentary MG-repaired muscles 2 wk postinjury]. These findings support further exploration of autologous minced MGs for the treatment of VML.
authors.affiliation: Extremity Trauma and Regenerative Medicine Research Program, United States Army Institute of Surgical Research, Fort Sam Houston, Texas.
authors.forename: B T
authors.initials: BT
authors.lastname: Corona
authors.forename: K
authors.initials: K
authors.lastname: Garg
authors.forename: C L
authors.initials: CL
authors.lastname: Ward
authors.forename: J S
authors.initials: JS
authors.lastname: McDaniel
authors.forename: T J
authors.initials: TJ
authors.lastname: Walters
authors.forename: C R
authors.initials: CR
authors.lastname: Rathbone
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D009043:Motor Activity; D009119:Muscle Contraction; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D012038:Regeneration; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014182:Transplantation, Autologous
chemical_list: D015415:Biomarkers; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1
keywords: minced muscle graft; skeletal muscle injury and damage; tissue engineering; tissue regeneration; volumetric muscle loss