Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

Abstract

Skeletal muscle is capable of robust self-repair following mild trauma, yet in cases of traumatic volumetric muscle loss (VML), where more than 20% of a muscle's mass is lost, this capacity is overwhelmed. Current autogenic whole muscle transfer techniques are imperfect, which has motivated the exploration of implantable scaffolding strategies. In this study, the use of an allogeneic decellularized skeletal muscle (DSM) scaffold with and without the addition of minced muscle (MM) autograft tissue was explored as a repair strategy using a lower-limb VML injury model (n = 8/sample group). We found that the repair of VML injuries using DSM + MM scaffolds significantly increased recovery of peak contractile force (81 -3% of normal contralateral muscle) compared to unrepaired VML controls (62 -4%). Similar significant improvements were measured for restoration of muscle mass (88 -3%) in response to DSM + MM repair compared to unrepaired VML controls (79 -3%). Histological findings revealed a marked decrease in collagen dense repair tissue formation both at and away from the implant site for DSM + MM repaired muscles. The addition of MM to DSM significantly increased MyoD expression, compared to isolated DSM treatment (21-fold increase) and unrepaired VML (37-fold) controls. These findings support the further exploration of both DSM and MM as promising strategies for the repair of VML injury.

Contribution of minced muscle graft progenitor cells to muscle fiber formation after volumetric muscle loss injury in wild‐type and immune deficient mice

“…; Kasukonis et al. ) have demonstrated muscle fiber regeneration following minced graft implantation in a VML defect, and herein we have definitively demonstrated a significant contribution of donor muscle progenitor/stem cell in this mouse model. Collectively, these findings support the biological requirement of myogenic stem/progenitor cell co‐delivery with a myoconductive scaffold to achieve appreciable muscle fiber regeneration after VML injury, for example, approximately one‐third of the muscle fibers lost after injury (Figs.…”

“…; Kasukonis et al. ). However, minced graft repair of the quadriceps did not improve strength earlier post‐injury (~1 month) despite some histological indication of muscle fiber regeneration (Li et al.…”

“…In previous studies, the repair of TA muscle VML injury using minced grafts has promoted significant functional improvements at 2-4 months post-injury (Corona et al 2013a;Garg et al 2014b;Kasukonis et al 2016). However, minced graft repair of the quadriceps did not improve strength earlier post-injury (~1 month) despite some histological indication of muscle fiber regeneration (Li et al 2014).…”

“…While this approach has various potential biological and practical strengths, autologous minced muscle grafts are currently limited to the repair of small VML defects due to availability of and morbidity with sourcing autologous muscle tissue. However, the strengths and weaknesses of autologous minced muscle grafts and acellular biological scaffolds may complement each other, wherein biological scaffolds may offer volume expansion to minced grafts and the minced grafts provide a in situ source of myogenic progenitors and stem cells Kasukonis et al 2016).…”

Decellularized Tissue for Muscle Regeneration

“…Based on the above points, it is not surprising that acellular scaffolds derived form a range of different tissues have already been tested in animal models [20,21,22,23,24,25,26,27,28,29,30,31,32,33,34] and in small cohorts of patients affected by VML [35,36]. …”