Bioresorbable filaments enhance nerve regeneration

Although axonal regeneration does occur after injury in the peripheral nervous system (PNS), growth across a gap and functional restoration is as yet an unmet challenge. To improve axonal and functional nerve regeneration, we examined bioresorbable neural stents designed to organize cellular migration and direct axon growth across a lesion. Extruded and drawn (6:1) poly(L-lactide) (PLLA) (MW 200 kD) filaments were bundled, placed into silicone tubes (2 mm O.D., 1.5 mm I.D.) and used to bridge a 10-mm gap in the rat sciatic nerve. Empty silicone tubes served as controls. In a companion experiment, filament packing densities of 0% (0 filament), 3.75% (16), 7.5% (32), 15% (64), and 30% (128) with wet-spun PLLA filaments (MW 200 kD) were tested. After 10 weeks, animals were perfused and implants were prepared for histological analyses. Light microscopy and TEM both showed improved regeneration for extruded and wet-spun filaments versus controls, in terms of nerve cable formation and number of myelinated axons bridging the gap. In addition, the morphology of the regenerated nerve segment was similar to the multifascicular structure of uninjured nerve. Filament packing densities of 3.75-7.5% gave the best in improvement of nerve regeneration. We demonstrate that PLLA filament bundles enhance the extent and consistency of nerve regeneration across a gap. The results suggest that our PLLA filament bundles might be used to establish functional connectivity after nerve injury.