The 2003 Annual Meeting of OASYS_NEW

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In Vivo and in Vitro Evaluation of a Synthetic Hydrogel Tube to Repair Rat Sciatic Nerve Injury Gaps

Belkas J1, Munro CA2, Dalton P3, Enescu C3, Goraltchouk A3, Shoichet M3, and Midha R2. (1) Division of Neurosurgery, University of Toronto, Sunnybrook and Women's College of Health Sciences Centre, 2075 Bayview Avenue, A131, Toronto, ON, Canada, (2) Division of Neurosurgery, Sunnybrook & Women's College HSC, University of Toronto, R106, 2075 Bayview Ave, Toronto, ON, Canada, (3) Dept. of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada

Artificial grafts are promising alternatives to nerve grafts for peripheral nerve repair, but require optimization of biomechanical properties for long-term success. We have synthesized poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous tubes and studied their efficacy in vivo. Specifically we studied the short and long-term stability, biocompatibility and regenerative capacity of 12mm long tubes for the repair of surgically created 10 mm nerve gaps in rat sciatic nerves. Tubes were analysed in vitro for their mechanical properties. Specifically, a micro-mechanical tester was used to measure the compressive modulus of tubes prior to implantation. Tubes with varying moduli were compared in terms of displacement achieved with load applied and these results served as a calibration curve for tube compression in vivo. For example, using the in vitro data, we created a calibration curve for load vs. displacement of y=6.6247x + 0.0321 (R2=0.9503, n=28). Using this curve, we were able to estimate the load applied in vivo at 8 weeks to be 1.94g ± 0.45g based on morphometric analysis of tubes, where a displacement was estimated at 0.288mm ± 0.0629mm (n=5). In on-going research, we are determining the loads applied in vivo after 4, 8, and 16 weeks. In vivo, tubes were assessed for collapse and for their ability to support nerve regeneration. Degree of collapse was determined with morphometry while nerve regeneration was assessed electrophysiologically, histologically and by the dry mass of the reinnervated lateral gastrocnemius (LG) muscle. At the 4 and 8 week timepoints, no collapse was seen but by 16 weeks 65 % of the tubes were at least partially collapsed. A regenerative tissue cable was seen in all tubes at all timepoints. Regeneration through autografts at 16 weeks was significanlty better (p <0.05) than through tubes by electrophysiologic analysis and dry LG mass. Histologic analysis is ongoing. Overall, we found that PHEMA-MMA tubes maintain their structural integrity at the early timepoints but partially collapse with time in vivo. To overcome this, we are pursuing two strategies: (1) improving the tube design to overcome patency issues; and (2) designing new polymers that will degrade over time to overcome the effects of time on collapse.