A Novel, Biodegradable Polymer Conduit Delivers Neurotrophins and Promotes Nerve Regeneration

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Abstract
Objective/Hypothesis: A wide variety of substances have been shown to promote neuritic extension after nerve injury. An obstacle to achieving the maximal benefit from these substances has been the difficulty in effectively delivering the substances over a protracted time course that promotes maximal, directed growth. In this study the delivery of a growth-promoting substance 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 of this study were to create a growth factor-loaded biodegradable nerve guidance conduit, and to assess in vivo nerve regeneration through the conduit compared with that through conduits lacking the substance. Materials/Methods: Inosine, a purine analogue thought to promote axonal extension following neural injury, was loaded into cylindrical polymer foams composed of a polylactide-co-glycolide copolymer. First, in vitro extravasation of inosine was measured over a several week period using spectrophotometry. Second, the foams were fashioned into single-channel cylindrical nerve guidance conduits 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 conduits lacking inosine were implanted into another set of animals as controls (n=12). Results: In vitro spectrophotometric measurements indicated appreciable leaching of inosine from the loaded foams over a period of at least 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%, respectively). A difference was also found in mean fiber diameter between the two groups, with the inosine-loaded tubes showing a statistically significantly larger diameter than controls (P < .05). Conclusions: A nerve regeneration conduit was successfully created that delivers growth promoting substances over a protracted time course. In an in vivo model, the presence of inosine, a purine analogue, yielded neural regeneration whose histological features suggest possible superior long-term motor function.