| A number of biomedical devices are being used or developed for the treatment of central nervous system (CNS) disorders including drainage shunts, catheters, dural substitutes, stimulating and recording electrodes, drug delivery systems, cell encapsulation devices, and nerve bridging and guidance devices. Regardless of the application, most indwelling devices by necessity traverse the meningeal covering of the brain or spinal cord. In some cases, contact with adjacent meningeal tissue is chronic, eliciting a fibrotic wound healing response that culminates in formation of a glial-fibroblastic scar composed of interwoven cell processes and disorganized extracellular matrix (ECM). Scar formation can reduce the effectiveness of many therapeutic devices including inhibiting neuronal regeneration in nerve guidance devices.; Device function and the regeneration of damaged neurons may be improved through strategies that mediate the fibrotic response. Toward this end, we hypothesized that surface chemistry can influence meningeal colonization, and that biomaterial nanotopographic features can alter the organization of secreted meningeal matrix proteins to alter the outgrowth of adjacent regenerating sensory nerve fibers. This work encompasses three major phases of research. Phase I describes the isolation and characterization of an early postnatal rat meningeal culture. Phase II investigates whether substrate surface chemistry is sufficient to alter meningeal cell behavior and matrix production. Phase III examined whether substrate topography is sufficient to alter the organization of meningeal cells and if so whether the changes altered the organization of adjacent regenerating sensory neurons. Results indicated that initial differences were apparent in meningeal attachment, spread cell area, and proliferation as a function of substrate hydrophobicity. Over time, however, the meningeal cultures produced abundant ECM and reached confluence on most of the materials, regardless of underlying surface chemistry. Grooved substrate nanotopography induced organization in the meningeal monolayer and its secreted matrix, such that adherent neurons expressed lengthened outgrowth with orientation biased in the direction of the grooves. These studies suggest that material physicochemical properties may be influential in directing the fibrotic response for improved neuronal regeneration at the host-material interface. |
