Over 2 million surgical operations are carried out on the central nervous system each year in the United States including over 125,000 laminectomies exposing the spinal cord. Adhesive scarring between the dura and surrounding tissues, as well as tethering of the spinal cord to the dura, are serious complications of spinal cord surgery. In blunt-impact spinal cord injury, the incidence of dural adhesion is especially high due to local injury to the meninges. We hypothesize that a synthetic, degradable, porous, cell-impermeable electrospun barrier device will effectively prevent subdural and epidural adhesions. Device design will be optimized through tailored chemical composition and architecture. Tyrosine- derived polycarbonate chemistry can be modified through copolymerization to vary protein adsorption and degradation rate. The electrospinning process can produce cell permeable and cell impermeable architectures. The biological performance of a two-by-two matrix of permeable versus non-permeable architecture and protein adsorbent versus non-adsorbent chemistry will be evaluated. The primary criteria for device design are to prevent the production of a continuous scar across the device and minimal inflammatory response around the implant. In vitro, test scaffolds will be evaluated for fibroblast penetration into and cytoskeletal organization on the membrane by fluorescence microscopy. As an in vitro predictor of inflammatory response, macrophage cytokine secretion will be measured by RayBio Rat Cytokine Antibody Array assays and verified by quantitative real time reverse transcriptase polymerase chain reaction assays for production of cytokine mRNAs. Test scaffold epidural adhesion performance will be evaluated in a rat non-injury laminectomy model. Mallory trichrome staining will reveal if a continuous collagen scar is formed across the device, and severity of inflammatory response will be evaluated by thickness of fibrous capsule, macrophage density, and presence of foreign body giant cells. With these results, either refinements will be made to the scaffold chemistry or architecture, or the scaffold will be tested for epidural and subdural anti-adhesion performance in a rat spinal cord injury model, scored by the Keck Center's adhesion scoring system. The proposed work will provide interdisciplinary training in support of the applicant's career goals while addressing a significant clinical need in spinal cord surgery. ? ? ?
