Browsing by Subject "PEGylated fibrin"
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Item Functional recovery of a volumetric skeletal muscle loss injury using mesenchymal stem cells in a PEGylated fibrin gel seeded on an extracellular matrix(2012-12) Merscham, Melissa Marie; Farrar, Roger P.; Suggs, Laura JThis study investigated the effect of bone marrow derived mesenchymal stem cells (MSCs) in a PEGylated fibrin gel (PEG) seeded into a decellularized extracellular matrix (ECM) on recovery of skeletal muscle following a volumetric muscle loss (VML) injury. Six to nine month old male Sprague-Dawley rats were used in this study. Approximately one-third of the skeletal muscle mass of the lateral gastrocnemius (LGAS) was removed from the LGAS, which was immediately replaced with an acellular ECM of the same dimensions. Seven days after injury, animals were injected with one of four solutions: saline (SAL), MSCs (MSC), PEGylated fibrin hydrogel (PEG), or MSCs in PEG (PEG+MSC). Maximal isometric tetanic tension (Po) of the LGAS was assessed fifty-six days after VML injury, followed by histological evaluation. VML injury resulted in a functional impairment of the LGAS capable of producing 76.1± 4.9% of the force generated in the non-injured contralateral LGAS. Tetanic tension of the PEG+MSC treated group was significantly higher compared to all other treatment groups (p < 0.05), although specific tension (N/cm2) in the PEG+MSC group (79.7±4.0%) was only significantly higher compared to SAL (58.2±3.0) and PEG (64.0±2.1%) treated groups (p < 0.05). However, LGAS mass was significantly higher in the PEG+MSC group compared to all other groups (p < 0.05). These findings suggest the combination of the PEG+MSC did not lead to a significant increase in muscle function compared to MSC treatment alone, and demonstrates the importance of MSCs in skeletal muscle regeneration in VML injury models. However, as evident by the significant increase in LGAS mass, PEG+MSC treatment may lead to histological differences not evaluated in this study. Gross morphology of the repaired gastrocnemius was indistinguishable from the contralateral control.Item SDF-1/IGF-1 conjugated to a PEGylated fibrin matrix as a treatment for an ischemia reperfusion injury in skeletal muscle repair(2012-12) Pham, Chantal Bich Phuong; Farrar, Roger P.; Suggs, Laura JIschemia/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.