INTELLECTUAL MERIT: The project seeks to increase the understanding of the effects of biomaterial surface properties on nerve regeneration. A nerve cell growth conduit fashioned from FDA approved, biodegradable poly(caprolactone) (PCL) will be modified on the inner surface with various peptides to test the hypothesis that the incorporation of a polypeptide that has shown preferential Schwann cell adhesion over fibroblast adhesion in vitro may improve nerve regeneration in vivo. Schwann cells play important roles in peripheral nerve regeneration, including delivery of cytokines and growth factors, whereas fibroblasts may induce scarring and inhibit nerve growth. The inner surface of the guide will be coated with synthetic peptides, i.e., laminin-derived arg-gly-asp (RGD) and poly(L-lysine) (PLL) known to promote Schwann cell adhesion. The effectiveness of the surface-modified guides will be assessed in vivo using a 1.5 cm sciatic nerve defect in a Lewis rat model.
BROADER IMPACTS: An improved guide for nerve cell regeneration could have important consequences for the 200,000 cases per year in the US where interventions for peripheral nerve injuries are required. In too many cases today the regeneration is so slow that the target muscle has atrophied before the nerve is reconnected. The PI will continue her practice of involving women and under represented minority graduate and undergraduate students in her research group. She will also continue to run the Research Opportunities for High School Students program (ROHSS), which she initiated in 2003 and which is geared toward female high school students. It is proposed now to enhance this program and extend it to an 8-week summer session. The PI involves her graduate students in this effort in order to encourage them to give back to the community as they pursue their own independent careers. The PI has also formed the Pittsburgh Biomaterials Group which is sponsored by the McGowan Institute for Regenerative Medicine. This group includes over 50 of the biomaterials researchers in the area. It meets monthly, and the ROHSS participants are invited to these meetings.