Cell-Derived Extracellular Matrix Fiber Scaffolds Improve Recovery from Volumetric Muscle Loss

There are currently no surgical procedures that effectively address the treatment of volumetric muscle loss (VML) injuries that has motivated the development of implantable scaffolding. In this study, the effectiveness of an allogenic scaffold fabricated using fibers built from the extracellular matrix (ECM) collected from muscle fibroblast cells during growth in culture was explored using a hindlimb VML injury (tibialis anterior muscle) in a rat model. Recovery outcomes (8 weeks) were explored in comparison with unrepaired controls as well previously examined allogenic scaffolds prepared from decellularized skeletal muscle (DSM) tissue (n = 9/sample group). At 8-week follow-up, we found that the repair of VML injuries using ECM fiber scaffolds in combination with an autogenic mince muscle (MM) paste significantly improved the recovery of peak contractile torque (79% +/- 13% of uninjured contralateral muscle) when compared with unrepaired VML controls (57% +/- 13%). Similar significant improvements were measured for muscle mass restoration (93% +/- 10%) in response to ECM fiber+MM repair when compared with unrepaired VML controls (73% +/- 13%). Of note, mass and contractile strength recovery outcomes for ECM fiber scaffolds were not significantly different from DSM+MM repair controls. These in vivo findings support the further exploration of cell-derived ECM fiber scaffolds as a promising strategy for the repair of VML injury with recovery outcomes that compare favorably with current tissue-sourced ECM scaffolds. Furthermore, although the therapeutic potential of ECM fibers as a treatment strategy for muscle injury was explored in this study, they could be adapted for high-throughput fabrication methods developed and routinely used by the textile industry to create a broad range of woven implants (e.g., hernia meshes) for even greater clinical impact. Impact statementVolumetric muscle loss (VML) overwhelms the body's natural ability to repair itself and still has no effective treatment. In this article, we present a novel method of generating fibers from extracellular matrix (ECM) proteins released by muscle-derived fibroblasts in vitro. The fibers can be assembled into scaffolds that replicate the structure of native muscle. Testing in animal models shows that the ECM fibers created through this method have the potential to be used to repair VML injuries, among other possible applications.