SDF-1/IGF-1 conjugated to a PEGylated fibrin matrix as a treatment for an ischemia reperfusion injury in skeletal muscle repair
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Ischemia/reperfusion (I/R) injury causes extensive damage to skeletal muscle, often resulting in prolonged functional deficits. This current study determines the efficacy of controlled release of SDF-1α and IGF-1 by conjugation to biodegradable, polyethylene glycol, (PEG)ylated fibrin gel matrix in skeletal muscle repair of an I/R injury. Male Sprague-Dawley rats underwent a 2-hour tourniquet induced I/R injury on their hind limbs. Twenty-four hours post injury the following treatments were administered: PEGylated fibrin gel (PEG-Fib), SDF-1 conjugated PEGylated fibrin gel (PEG-Fib/SDF-1), or dual protein IGF-1 and SDF-1 conjugated PEGylated fibrin gel (PEG-Fibrin/SDF-1/IGF-1. Following 14 days after injury, functional and histological evaluations were performed. There was no significant difference in maximum tetanic force production recovery between PEG-Fib and PEG-Fib/SDF-1 groups. However, PEG-Fib/SDF-1/IGF-1 group resulted in significant improvement of force production relative to the other treatment groups. The same results were found for specific tension. Histological analysis revealed a greater distribution of small myofibers in the PEG-Fib/SDF-1 group than the PEG-Fib group, while the PEG-Fib/SDF-1/IGF-1 group had the smallest distribution of small fibers and similar to controls (uninjured). There were also a greater number of centrally located nuclei in the PEG-Fib/SDF-1 group than the PEG-Fib group, while the PEG-Fib/SDF-1/IGF-1 group had similar values to controls. Although these results confirm the protective role of exogenous IGF-1, SDF-1 did not have an effect on skeletal muscle repair.