Reorganization and orientation of peripheral nerve fibers regenerating through a multiple-lumen silicone rubber cuff: An experimental study using the sciatic nerve of rats

A silicone rubber double-tube, seven-lumen nerve cuff was designed and fabricated. In vivo studies were done to test its feasibility for peripheral nerve repair. The right sciatic nerve was transected at the mid-thigh level in adult male Sprague-Dawley rats. The proximal and distal stumps were inserted into both ends of the seven-lumen cuff to form a 5 mm gap between stumps in sixteen animals for 8, 12, 16, and 24 weeks implantation periods. The gap was successfully bridged by regenerating nerve tissue in the seven-lumen cuff repairs at all four post-implantation periods. Histological studies showed that the regenerating axons formed between one and seven nerve bundles as they regenerated across the gap in the seven-lumen cuff repairs. Each of these nerve bundles infiltrated a lumen in the seven-lumen cuff. The spatial arrangement or orientation of these nerve bundles inside the seven-lumen cuffs was determined by the pattern of holes in the cuffs. The histologic structure of these nerve bundles showed a two zone reorganization with an outer peripheral zone constituted mainly of connective tissue and numerous blood vessels and an inner central zone which contained mostly axons in different stages of maturation. A marked difference between the experimental seven-lumen cuff repairs and control silicone rubber single-lumen cuff repairs and end-to-end anastomosis repairs was evident in the distal stump's reorganization. In the control single-lumen cuff and end-to-end repairs, the nerve regenerated through the distal stump forming one central, large nerve bundle. In the seven-lumen cuff repairs, the regenerating axons formed several much smaller nerve bundles whose orientation followed the same pattern as seen at the middle of the repair site in the seven-lumen cuffs. Regenerated axon populations at middle and distal repair regions were comparable in the seven-lumen cuffs to that seen in the single-lumen controls in spite of a 2.5x reduction in total cross-sectional area in the seven-lumen cuff vs. single-lumen cuff. This indicated higher densities of regenerated axons in the seven-lumen cuff repairs as compared to the single-lumen cuff repairs. At 16 and 24 weeks post-operatively, integrated compound action potential area ratios were comparable among the seven-lumen cuff repairs and the single-lumen and end-to-end repair controls. At 16 and 24 weeks, functional recovery assessments, from video recordings of the animals with the seven-lumen cuff repairs, were closer to normal control rats than the assessments obtained from animals with the single-lumen and end-to-end repairs.