Peripheral nerve regeneration through tubular devices : a comparison of assays of device effectiveness

Abstract

Peripheral nerve injury affects nearly 200,000 patients annually in the United States and unless treated results in paralysis of skeletal muscle and loss of sensation. Previous studies in this laboratory have focused on comparing the effectiveness of various tubular devices in repairing experimental nerve injuries in an animal model. The devices were rank-ordered based on clinically relevant assays of regeneration such as number regenerated nerve fibers and electrophysiological conduction properties of the regenerated nerves. Such assays provide a useful measure of the clinical efficacy of devices but require long-term (up to 60-week) studies in order to obtain meaningful results. There exists a need for a short-term (less than 12-week) assay with which nerve repair devices can be compared. The overall goal of this thesis was to establish an experimental assay that can be used to detect statistically significant differences among nerve repair devices in short-term studies. In this thesis, four different assays of nerve regeneration were compared on the basis of their appropriateness to quantify the regeneration promoted by nerve repair devices in studies less than 12 weeks in duration. An acceptable assay must reach a plateau with time during short-term studies and must yield a quantitative metric with which nerve devices can be compared. The results of this thesis suggest that an assay based on ability of a nerve repair device to promote reinnervation across nerve gaps of various lengths meets the criteria for an acceptable assay. The data also indicate that the characteristic gap length (Lc), which is derived from curve-fitting the experimental data for reinnervation versus gap length, can be used as a quantitative metric of nerve regeneration. The experimental data indicate that for the silicone tube device, the value of Lc reached a plateau with time before 9 weeks, and the standard error in L was less than 5 percent of the value in two different nerve repair models (single-leg and crossanastomosis). The data also suggest that statistically significant differences between the silicone tube device and a collagen-based device (the CG device) are obtainable during short-term (12-week) studies.