Therapeutic Effect of a Recombinant Human Fibronectin Construct in Skeletal Muscle Repair and Oxidative Stress.

Aging mice experience a depletion of muscle extracellular matrix fibronectin (FN). Therefore, enhancing FN expression in the aging tissue microenvironment may be able to maintain satellite cell function and facilitate the repair of damaged skeletal muscle. Herein, we have used molecular dynamics (MD) simulations to select FN functional domains, which were combined into a single construct, rhFN-NM (recombinant human Fibronectin-N-terminal module). The antioxidant properties of this construct were tested at the cellular level and included effects on cell adhesion, anti-aging, apoptosis and expression of aging-related proteins. When used in an animal skeletal muscle injury model, naturally aging mice, or in IL-10(-/-) gene knockout mice, this construct promoted skeletal muscle repair and improved the immune microenvironment of the tissue. Overall, we show that the construct rhFN-NM improves skeletal muscle repair and protects against oxidative stress.