Ethylene Oxide Sterilization Preserves Bioactivity and Attenuates Burst Release of Encapsulated Glial Cell Line...

Synthetic nerve guides are widely utilized to reconstruct peripheral nerve defects that are less than three centimeters. However, there are no clinically available nerve guides that are approved to promote repair over long gaps (>3 cm). Many currently available guides are unable to sustain large defect regeneration either because of limitations in fabrication or short degradation times in vivo. Furthermore, current clinically available nerve guides do not contain neurotrophic factor delivery systems to promote nerve tissue regeneration over long gaps. The purpose of this paper is to describe the manufacturing parameters and sterilization procedures of a 5.2 cm poly(caprolactone) nerve conduit with embedded polymeric microspheres that encapsulate glial cell line-derived neurotrophic factor (GDNF) for implantation into a preclinical rhesus macaque 5 cm median nerve defect model. Nerve conduits were sterilized with room temperature ethylene oxide (RT EtO) and assessed for morphology as well as maintenance of porosity. Release kinetics and bioactivity of GDNF were also assessed in RT EtO sterilized guides. Scanning electron microscopy indicated that RT EtO treatment did not affect morphology and porosity percentage of nerve guides. Furthermore, RT EtO had no effect on GDNF bioactivity based on Schwannoma cell migration studies. RT EtO guides exhibited significantly slowed GDNF release compared to GDNF release from nonsterile guides indicating that EtO treatment may enhance the long-term delivery kinetics of GDNF from polymeric microspheres within the nerve guide.