Optimizing Muscle Function in Composite Tissue Injuries with Segmental Bone Defects
Abstract
The goal of this proposal is to determine how treatment of a segmental bone defect (SBD) affects function and composition of adjacent muscle in a porcine composite tissue injury (CTI) model. To date, the majority of CTI investigations have focused on the effects of muscle injury on bone healing. In our current ongoing work and have determined that a SBD leads to loss of myogenic proteins, increases in fibrosis, and loss of strength in adjacent uninjured muscle. This opens investigative opportunities to improve muscle function in limbs with CTI. We propose to investigate how two strategies, currently used clinically for SBD management, affect function and composition of the adjacent muscle. Our project is aligned with the PRORP Focus Area: Composite Tissue Regeneration specifically investigating techniques aimed at improving outcomes following high-energy extremity trauma, with a focus on improving neuromuscular recovery following CTI. We have developed an in vivo CTI model in Yucatan minipigs that includes a tibial diaphyseal SBD and an adjacent volumetric muscle defect (VML). Our model offers a translational vehicle uniquely designed to quantify biologic tissue interactions between muscle and bone. In our most recent work, pigs with SBDs, with or without an adjacent VML injury, lost 50% of muscle torque and had nearly identical adverse changes in muscle protein and fibrous composition three months after injury in muscle adjacent to the SBD. Collectively our data indicate that an untreated SBD is a primary source of muscle deterioration in a CTI injury. In current clinical practice SBDs are typically treated acutely with either 1) staged therapy predicated by sterilizing the SBD with antibiotic-impregnated polymethylmethacrylate (PMMA) followed by delayed bone grafting or 2) with therapies designed to acutely reconstitute bone healing, typically with autogenous bone grafting or bone-morphogenetic protein.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2024
- Accession Number
- AD1230227
Entities
People
- Roman M Natoli
Organizations
- Indiana University