Tacrolimus as an adjunct to autologous minced muscle grafts for the repair of a volumetric muscle loss injury

Benjamin T Corona,Sarah M Greising,Jessica C Rivera,Joseph C Wenke

doi:10.1186/s40634-017-0112-6

Benjamin T Corona, Sarah M Greising + Show 2 more

Open Access

https://doi.org/10.1186/s40634-017-0112-6

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Abstract

BackgroundVolumetric muscle loss (VML) following extremity orthopaedic trauma or surgery results in chronic functional deficits and disability. A current translational approach to address the devastating functional limitations due to VML injury is the use of an autologous minced muscle graft (~1 mm3 pieces of muscle tissue) replacement into the injured defect area, although limitations related to donor site morbidity are still unaddressed. This study was designed to explore adjunct pharmacological immunomodulation to enhance graft efficacy and promote muscle function following VML injury, and thereby reduce the amount of donor tissue required.FindingsUsing a validated VML porcine injury model in which 20% of the muscle volume was surgically removed, this study examined muscle function over 3 months post-VML injury. In vivo isometric torque of the peroneus teritus (PT) muscle was not different before surgery among sham, non-repaired, non-repaired with tacrolimus, graft-repaired, and graft-repaired with tacrolimus VML groups. Bi-weekly torque analysis of the VML injured musculature presented a significant strength deficit of ~26% compared to pre-injury in the non-repaired, non-repaired with tacrolimus, and graft-repaired groups. Comparatively, the strength deficit in the graft-repair with systemic tacrolimus was marginally improved (~19%; p = 0.056). Both of the minced graft repaired groups presented a greater proportion of muscle tissue in full-thickness histology specimen.ConclusionsWe demonstrate that adjunctive use of tacrolimus with an ~50% minced muscle graft replacement resulted in modest improvements in muscle function 3 months after injury and repair, but the magnitude of improvement is not expected to elicit clinically meaningful functional improvements.

Highlights

We demonstrate that adjunctive use of tacrolimus with an ~50% minced muscle graft replacement resulted in modest improvements in muscle function 3 months after injury and repair, but the magnitude of improvement is not expected to elicit clinically meaningful functional improvements
Extremity orthopaedic trauma that results in volumetric muscle loss (VML) presents chronic and persistent functional muscle deficits, restricted joint range of motion, and fibrosis, which manifest as chronic disability (Mase et al 2010; Corona et al 2015; Garg et al 2015; Rivera and Corona 2016)
Sections from peroneus teritus (PT) muscles that were repaired with a muscle graft presented noticeably lesser fibrotic tissue and greater muscle tissue than non-repaired Volumetric muscle loss (VML) injured muscles, regardless of tacrolimus delivery

Summary

Introduction

Extremity orthopaedic trauma that results in volumetric muscle loss (VML) presents chronic and persistent functional muscle deficits, restricted joint range of motion, and fibrosis, which manifest as chronic disability (Mase et al 2010; Corona et al 2015; Garg et al 2015; Rivera and Corona 2016). Recent basic and translational research efforts are aimed at promoting de novo regeneration of the muscle tissue to ameliorate musculoskeletal regeneration and to promote long-term improvements in muscle and limb function (Corona and Greising 2016). In both small and large animal models treatment of VML injuries with autologous minced muscle grafts (~1 mm pieces of muscle tissue) have the ability to improve muscle function (Corona et al 2013; Garg et al 2014; Li et al 2014; Aurora et al 2015; Ward et al 2015; Kasukonis et al 2016; Ward et al 2016). This study was designed to explore adjunct pharmacological immunomodulation to enhance graft efficacy and promote muscle function following VML injury, and thereby reduce the amount of donor tissue required

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