The effect of microsphere delivered Nerve Growth Factor (NGF) in a poly-lactic-co-glycolic-acid (PLGA) 85/15 nerve conduit bridging a 10 mm rat sciatic nerve gap was assessed, comparing nine groups... Show moreThe effect of microsphere delivered Nerve Growth Factor (NGF) in a poly-lactic-co-glycolic-acid (PLGA) 85/15 nerve conduit bridging a 10 mm rat sciatic nerve gap was assessed, comparing nine groups (n = 6): PLGA conduits filled with saline, saline and NGF, saline with blank microspheres; four different NGF microspheres (5, 20, 50, and 100 mg/ml); an autologous graft and sciatic nerve gap. Histomorphometry, retrograde tracing, electrophysiology, and functional outcomes were evaluated up to 16 weeks. The autologous graft showed the largest fascicular area (0.65 mm(2)) and had a significantly greater number of myelinated fibers (P < 0.0001). Electrophysiology showed Compound Muscle Action Potential (CMAP) recordings for the autologous graft returning at 6 weeks after nerve transection, reaching their highest amplitude of 3.6 mV at endpoint. No significant differences were found in functional evaluation between groups or between conduits with microspheres and the saline filled conduit. A PLGA 85/15 nerve conduit is capable of sustaining nerve regeneration. The microsphere delivery system does not interfere with regeneration. (C) 2011 Wiley-Liss, Inc. Microsurgery 31:293-302, 2011. Show less
Regeneration of peripheral nerves after injury is suboptimal. We now report the long term delivery of nerve growth factor (NGF) by biodegradable poly-lactic-co-glycolic acid (PLGA) microspheres in... Show moreRegeneration of peripheral nerves after injury is suboptimal. We now report the long term delivery of nerve growth factor (NGF) by biodegradable poly-lactic-co-glycolic acid (PLGA) microspheres in vitro and in vivo. Lactic to glycolic acid ratios of 50:50 and 85:15 were fabricated using the double emulsion solvent, evaporation technique. Three different inherent viscosities (0.1 dL g(-1):1A 0.4 dL g(-1):4A, 0.7 dL g(-1):7A) were analyzed. In vitro, release of NGF for 23 days was measured. Electron microscopy demonstrated intact spheres for at least 7 days (50:50 1A), 14 days (50:50 4A), or 35 days (50:50 7A and 85:15 7A). In vitro release kinetics was characterized by burst release, followed by release of NGF at a rate of 0.6-1.6% a day. Release curves for 50:50 1A and 85:15 7A differed significantly from other compositions (p < 0.01). In vivo, release was characterized by a novel radionuclide tracking assay. Release rates varied from 0.9 to 2.2% per day with linear kinetics. All but the 85:15 type of spheres showed different release profiles in vivo compared to in vitro conditions. On the basis of the surface morphology and release profiles, we found microspheres fabricated from 50:50 4A PLGA to be best suited for the use in a rat sciatic nerve injury model. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 95A: 1067-1073,2010. Show less
Single channel conduits are used clinically in nerve repair as an alternative to the autologous nerve graft. Axons regenerating across single channel tubes, however, may disperse resulting in... Show moreSingle channel conduits are used clinically in nerve repair as an alternative to the autologous nerve graft. Axons regenerating across single channel tubes, however, may disperse resulting in inappropriate target reinnervation. This dispersion may be limited by multichannel nerve conduits as they resemble the structure of nerve multiple basal lamina tubes. In this study, we investigated the influence of channel number on the axonal regeneration using a series of 1-, 2-, 4-, and 7-channel collagen conduits and commercial (NeuraGen (R)) single channel conduits. Nerve conduits were implanted in rats with a 1 cm gap of sciatic nerve. After four months, quantitative results of regeneration were evaluated with nerve morphometry and the accuracy of regeneration was assessed using retrograde tracing: two tracers being applied simultaneously to tibial and peroneal nerves to determine the percentage of motor neurons with double projections. Recovery of function was investigated with compound muscle action potential recordings and ankle motion analysis. We showed that the fabricated 1-channel and 4-channel conduits are superior to other types of conduits in axonal regeneration. Simultaneous tracing showed a significantly lower percentage of motor neurons with double projections after 2- and 4-channel compared with 1-channel conduit repair. This study shows the potential influence of multichannel guidance on limiting dispersion without decreasing quantitative results of regeneration. (C) 2010 Elsevier Ltd. All rights reserved. Show less
