COX-2 inhibition does not alter wound healing outcomes of a volumetric muscle loss injury treated with a biologic scaffold.

Abstract

Volumetric muscle loss (VML) injuries are characterized by a heightened immune response that alters canonical wound healing outcomes and results in a chronic reduction of both total myofiber number and functional capacity. Preclinical and clinical investigations aimed at repairing VML injuries have largely utilized biologic scaffolds (BSs) as a potential therapeutic intervention. BSs rely on the recruitment of a myriad of host-derived immune, stem, and stromal cells to induce a wound healing response that has been routinely characterized as largely fibrous matrix deposition and limited myofiber regeneration at the site of the defect. While the mechanisms by which this occurs are not fully elucidated, the role of the immune response and modulation thereof is believed to be critical to BS-mediated wound healing outcomes. Given the known roles of nonsteroidal anti-inflammatory drugs (NSAIDs) on cyclooxygenase (COX) signaling and of COX signaling on macrophage polarization and myogenesis, it is plausible that prescription of NSAIDs could alter BS-mediated VML repair. To study the effect of COX-2 inhibition on BS-mediated repair of VML, an established rat model of VML was acutely treated with BSs with and without adjunct administration of mavacoxib, a COX-2-specific inhibitor. Evaluation of the function of the affected musculature as well as the tissue-level histomorphology, evaluated at 14 and 90 days postoperatively, suggested that COX-2 inhibition does not alter the baseline repair outcomes of the BS therapy. These studies provide useful information to clinicians regarding the postoperative prescription of NSAIDS in concert with a BS therapy in the treatment of VML.