Porcine urinary bladder matrix does not generate appreciable de novo muscle tissue in rat models of volumetric muscle loss injury

Abstract

Event Abstract Back to Event Porcine urinary bladder matrix does not generate appreciable de novo muscle tissue in rat models of volumetric muscle loss injury Amit Aurora1, Janet L. Roe1, Benjamin T. Corona1 and Thomas J. Walters1 1 US Army Institute of Surgical Research, Extremity Trauma Research and Regenerative Medicine, United States Background: The high prevalence of volumetric muscle loss (VML) among battlefield injuries has stimulated research efforts aimed at regenerating muscle de novo using tissue engineering approaches. Extracellular matrix (ECM) scaffolds, in particular, have been extensively used based on their ability to provide a bio-inductive platform that supports endogenous cell recruitment, proliferation, and differentiation, ultimately improving healing of the tissue[1][2]. Recently, surgeons have used commercially available porcine derived urinary bladder matrix (UBM) to repair lower extremity VML in a small cohort of patients[3][4]. The porcine UBM scaffold has clinically been used for surgical reinforcement of soft tissue where weakness exits and general wound management-indications for which it has been approved by the U.S. Food and Drug Administration. However, there is need to establish evidence that will support further clinical use of the scaffold for the repair of traumatic muscle injuries. The overarching objective of this study is to investigate the efficacy of the porcine UBM scaffold as a tissue engineered strategy for the repair of traumatic muscle injuries. Methods: A musculotendinous junction (MTJ) or volumetric muscle loss (VML) injury was created in Lewis rats. For the MTJ injury, the defect created either received no repair or was repaired with a 6-layer MatriStem Surgical Matrix PSMX (time points: 2, 4, or 8 weeks). For the VML injury, the defect created received no repair, repaired with autograft tissue or with a 3-layer MatriStem Surgical Matrix PSM (time points: 2, 8, or 16 weeks). The m-ECM was only investigated at 2 weeks. Upon finding that the porcine UBM scaffold partially restored the muscle function in VML injury at eight weeks; a second study was performed to determine if physical rehabilitation during an eight week period would further improve function. The porcine UBM repaired rats were given free access to running wheels beginning at one week or four weeks post - injury. In vivo function testing was done (MTJ injury: 4 weeks post-injury; VML injury: 8 and 16 weeks post-injury) followed by tissue harvest for histological analysis. Results and Discussion: The porcine UBM scaffold did not promote appreciable muscle tissue regeneration as demonstrated in two distinct models of extremity VML. The porcine UBM scaffold completely resorbed when used as an interpositional graft for MTJ repair. When used to augment a VML defect surrounded by muscle and fascia, the porcine UBM scaffold improves the contractile properties of the injured limb by 17%, but does so without significant muscle fiber regeneration compared to autograft that showed robust regeneration (A-C). Finally, inclusion of physical rehabilitation (i.e., voluntary wheel running) did not improve tissue remodeling or functional improvements observed with scaffold implantation alone. Conclusions: The scaffold may not be suitable for clinical repair of MTJ injuries. The porcine UBM scaffold when used for VML repair may hasten functional recovery not due to significant muscle regeneration, but through force transmission via scaffold mediated fibrosis. The study suggests that if appreciable muscle generation is to be realized, combinatorial approaches that incorporate myogenic cells, a myoconductive scaffold, and a vasculogenic accelerant need to be developed.