Browsing by Subject "Functional recovery"
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Item The development of immunomodulatory approaches to restore skeletal muscle function after injury(2015-05) Rybalko, Viktoriya Yurievna; Farrar, Roger P.; Suggs, Laura J; Brothers, Robert M; Thompson, Wesley J; Adamo, Martin LEfficient restoration of skeletal muscle function after severe injury is a major goal of intervention therapies. Ischemia/reperfusion (I/R) injury to skeletal muscle leads to exaggerated inflammatory response and significant ultrastructural tissue damage slowing restoration of muscular structure and function. Herein, we used animal model of tourniquet-induced ischemia/reperfusion injury (TK-I/R) to test the effects of exogenously delivered growth factors and cells on skeletal muscle regeneration. The delivery of PEGylated fibrin along with stromal cell derived factor-1α and/or insulin-like growth factor-I into acutely injured muscle, differentially affected functional muscle regeneration. These data suggest that local balance and release kinetics of growth factors in the tissue microenvironment can significantly impact the success of skeletal muscle repair. Cell-mediated treatment of I/R-injured muscle demonstrated significant tissue regeneration using adoptively transferred and in vitro polarized macrophages. Functional activation status of transplanted macrophage populations impacted the outcome of muscle repair. We showed that increasing macrophage populations at the site of injury in temporally regulated manner is beneficial for efficient recovery of muscle force and function.Item Natural biomaterials for enhanced oligodendrocyte differentiation and spinal cord injury repair(2014-08) Geissler, Sydney Amelia; Stachowiak, Jeanne Casstevens; Schmidt, Christine E.Spinal cord injury is a devastating source of suffering in the spectrum of human pathophysiology; advancement for clinical therapy in this area has been stagnant in comparison to modern medical development. Current treatments are palliative, and functional recovery is minimal. During the first two weeks after injury, dense glial scar forms that is impenetrable by regenerating axons. Intervention is imperative to minimize scar formation and provide a supportive environment for axonal regeneration. Oligodendrocytes are critical to maintain the health of growing axons during development and after injury. Obtaining these cells through differentiation of neural progenitor cells (NPCs) is a viable option, but current clinical trials involving stem cells are plagued by poor cell survival and undirected differentiation. Research indicates that local extracellular matrix (ECM) is vital to progenitor differentiation and tissue regeneration. During development, spinal cord ECM is comprised of high concentrations of laminin and hyaluronic acid (HA), which provide essential cues to direct NPC migration and differentiation. The purpose of this research is to create a biomaterial optimized to direct NPC differentiation to oligodendrocytes. Natural biomaterials were optimized from distinct combinations of collagen I, HA, and laminin I to model the native ECM signals found during oligodendrocyte maturation. Four material combinations (collagen, collagen-HA-laminin, collagen-HA, and collagen-laminin) were fabricated into injectable hydrogels to mimic the range of compressive and shear mechanical properties present in neonatal central nervous system (CNS) tissue. Differentiation was assessed by culturing rodent fetal NPCs in these materials without specific soluble factors to direct cellular behavior. The three-component hydrogel performed optimally and achieved a 66% oligodendrocyte differentiation rate compared to approximately 15% in the collagen alone hydrogel. An in vivo study was then conducted using a rat contusion model of spinal cord injury with intervention using the injectable, three-component hydrogel seeded with rat NPCs. Functional recovery was assessed using six behavioral tests. Significant recovery was observed using two behavioral tests six weeks post-treatment. Lesion size was measured and correlated well with behavioral outcomes. The data obtained in this research indicate that a multi-component hydrogel mimicking native, developmental CNS tissue may address problems associated with current clinical practice.