A novel, biodegradable polymer conduit delivers neurotrophins and promotesnerve regeneration

Objective/Hypothesis: A wide variety of substances have been shown to promo te neuritic extension after nerve injury, An obstacle to achieving the maxi mal benefit from these substances has been the difficulty in effectively de livering the substances over a protracted time course that promotes maximal , directed growth. In this study the delivery of a growth-promoting substan ce through a biodegradable conduit, using materials originally designed for drug delivery applications, was hypothesized to promote more robust neural regeneration than through conduits lacking the substance. The objectives o f this study were to create a growth factor-loaded biodegradable nerve guid ance conduit, and to assess in vivo nerve regeneration through the conduit compared with that through conduits lacking the substance. Materials/Method s: Inosine, a purine analogue thought to promote axonal extension following neural injury, was loaded into cylindrical polymer foams composed of a pol ylactide-co-glycolide copolymer. First, in vitro extravasation of inosine w as measured over a several week period using spectrophotometry. Second, the foams were fashioned into single-channel cylindrical nerve guidance condui ts via a novel, low-pressure injection molding technique. The conduits were then used to bridge 7-mm defects in the rat sciatic nerve (n=8), Control c onduits lacking inosine were implanted into another set of animals as contr ols (n=12). Results: In vitro spectrophotometric measurements indicated app reciable leaching of inosine from the loaded foams over a period of at leas t 9 weeks. In the in vivo model, after 10 weeks, a higher percentage cross sectional area composed of neural tissue existed through the inosine-loaded conduits compared with controls (mean 44%, SD 7.5% vs. 36%, SD 8.6%, respe ctively). A difference was also found in mean fiber diameter between the tw o groups, with the inosine-loaded tubes showing a statistically significant ly larger diameter than controls (P < .05), Conclusions: A nerve regenerati on conduit was successfully created that delivers growth promoting substanc es over a protracted time course, In an in vivo model, the presence of inos ine, a purine analogue, yielded neural regeneration whose histological feat ures suggest possible superior long-term motor function.