Decellularized extracellular matrix repair of volumetric muscle loss injury impairs adjacent bone healing in a rat model of complex musculoskeletal trauma.

Background: Traumatic muscle loss (i.e., volumetric muscle loss injury; VML) impairs adjacent fracture healing, but is often left untreated. A promising therapy for this application is a decellularized extracellular matrix (ECM) due their capacity to regenerate a vascularized tissue bed. This study tested the hypothesis that repair of VML concomitant to fracture with a small intestine submucosa (SIS)-ECM improves musculoskeletal healing. Methods: In male Lewis rats (~375 grams), a 3 mm segmental tibia defect (SBD) was created in concomitance with a 6 mm full thickness VML injury to the adjacent tibialis anterior (TA) muscle. For all rats (n=10), the SBD was treated with internal plate fixation and delivery of rhBMP-2 (1 [mu]g) on a collagen sponge. The VML either had No Repair or SIS-ECM repair (n=5/group). Bone regeneration within the SBD (BV/TV) was assessed via in vivo [mu]CT at 2, 4, and 6 weeks and histology at 6 weeks post-injury. TA muscle in vivo strength and histological assessments were performed at 6 weeks post-injury. Results: Compared to No Repair, SIS-ECM presented -21% (p=0.09) and -27% (p=0.004) BV/TV at 4 and 6 weeks post-injury, respectively. At 6 weeks, the SBD gap length was shorter for the No Repair than the SIS-ECM (2.64+/-0.30 and 3.67+/-0.41 mm, respectively; p=0.09), while the distances from the end of each cortical segment to the center of the first stabilization screw were longer (1.86+/-0.25 and 0.85+/-0.30 mm, respectively; p=0.035), indicating enhanced resorption in the SIS-ECM group. Both groups presented similar magnitude TA muscle strength deficits compared to their contralateral limbs (10-150 Hz: No Repair, -58-67%; SIS-ECM, -51-74%). The TA muscle of the SIS-ECM group was remarkable for it presentation of fibrosis, edema, and immune cell presence. Conclusions: SIS-ECM VML repair impaired open fracture healing and failed to improve skeletal muscle strength. (C) 2016 Lippincott Williams & Wilkins, Inc.

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