Date of Award
Doctor of Philosophy
Chemical and Biological Engineering
Carole A. Heath
Nerve injuries complicate successful rehabilitation more than any other form of trauma because of loss of protective sensibility and tactile discrimination, denervation atrophy of muscles, and pain syndromes. While achieving full function and organ reinnervation after peripheral nerve injury is a challenge, a promising method of improving the rate and success of regeneration is the bioartificial nerve graft (BNG). The BNG developed in the laboratory consists of a porous bioresorbable tube containing cultured Schwann cells that help to direct and support nerve regeneration when used to bridge the gap between the ends of the severed nerve;To aid in the design of the BNG, a simple reaction and diffusion model has been developed to describe the transport and uptake of nutrients by cells in the graft. Implementation of the model has required experimental determination of several key parameters including nutrient diffusivities as a function of polymer porosity with and without the presence of Schwann cells, nutrient consumption rates, and productivity of nerve growth factor, a potent stimulator of regeneration;Conduits were created with varying porosities and wall thickness. Also, the effect of Schwann cell seeding density was evaluated. The ability of this bioartificial nerve graft to enhance the growth rate of neurons was then tested in vitro using dorsal root ganglia as the source of neurons. Growth was hindered in conduits with greater wall thicknesses and lower porosities. The computer model suggests that this is due to lack of oxygen within the lumen of the conduit. Maximum growth occurred at 75% porosity due to optimization of oxygen and nerve growth factor available to the axons. Reduction in growth for porosities above 75% is due to increased flux of growth factors out of the conduit. Higher Schwann cell seeding density enhances growth due to increased trophic support but leads to severe branching in both two- and three-dimensional systems.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Gregory Edward Rutkowski
Rutkowski, Gregory Edward, "Design of a bioartificial nerve graft " (1999). Retrospective Theses and Dissertations. 12163.