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

Beth E. Pollot, Stephen M. Goldman, Joseph C. Wenke, Benjamin T. Corona

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Traumatic muscle loss (i.e., volumetric muscle loss [VML] injury) impairs adjacent fracture healing but is often left untreated. A promising therapy for this application is a decellularized extracellular matrix (ECM) because of their capacity to regenerate a vascularized tissue bed. This study tested the hypothesis that repair ofVMLconcomitant to fracturewith a small intestine submucosa (SIS)-ECMimprovesmusculoskeletal healing. METHODS: In male Lewis rats (∼375 g), a 3-mmsegmental bone defect (SBD) was created in concomitancewith 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 recombinant human bone morphogenetic protein 2 (1μg) on a collagen sponge. TheVML either had no repair or SIS-ECM repair (n = 5/group). Bone regeneration within the SBD(BV/TV [bone volume as a fraction of total volume])was assessed via in vivomicro-computed tomography at 2, 4, and 6weeks and histology at 6 weeks after injury. Tibialis anterior muscle in vivo strength and histologic assessmentswere performed at 6 weeks after injury. RESULTS: Compared with no repair, SIS-ECMpresented -21%(p = 0.09) and -27%(p = 0.004) BV/TVat 4 and 6 weeks after injury, respectively. At 6 weeks, the SBD gap length was shorter for the no repair than that for the SIS-ECM (2.64 ± 0.30 and 3.67 ± 0.41 mm, respectively; p = 0.09), whereas the distances fromthe end of each cortical segment to the center of the first stabilization screw were longer (1.86 ± 0.25 and 0.85 ± 0.30mm, respectively; p = 0.035), indicating enhanced resorption in the SIS-ECMgroup. Both groups presented similar magnitude TA muscle strength deficits compared with their contralateral limbs (10-150 Hz: no repair, -58% to 67%; SIS-ECM, -51% to 74%). The TA muscle of the SIS-ECM group was remarkable for its presentation of fibrosis, edema, and immune cell presence. CONCLUSIONS: Small intestine submucosa-ECM VML repair impaired open fracture healing and failed to improve skeletal muscle strength. (J Trauma Acute Care Surg. 2016;81: S184-S190.

Original languageEnglish (US)
Pages (from-to)S184-S190
JournalJournal of Trauma and Acute Care Surgery
Issue number5
StatePublished - 2016
Externally publishedYes


  • Biological scaffold
  • Inflammation and resorption
  • Lewis rats
  • Open fracture
  • Skeletal muscle injury

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine


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