A collagen‐based nerve guide conduit for peripheral nerve repair: An electrophysiological study of nerve regeneration in rodents and nonhuman primates

Abstract

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS)

Assessment of Axonal Growth into Collagen Nerve Guides Containing VEGF‐Transfected Stem Cells in Matrigel

“…Axonal outgrowth, proceeding from the proximal stump through the substrate, is conditioned by the preceding events. The long-term functional recovery of nerve gaps in rodent and primate models using the collagen-based conduit are similar to primary anastomosis and autograft procedures (Archibald et al, 1991).…”

The sciatic nerve injury model in pre-clinical research

“…Yet, also SNI in primates has been used for pre-clinical testing of nerve scaffolds (Archibald et al, 1991) due to its closer similarities with human patients.…”

The Effect of Chick Embryo Cerebro-Spinal Fluid in Microwave Irradiated Collagen Guide Channel on Sciatic Nerve Regeneration in Rat

“…Artificial nerve conduit to bridge the gap between severed nerve stumps is widely accepted as a useful alternative that provides structural support and a favorable microenvironment for axonal regeneration [18]. The great advantage of collagen is very resorbable, and Archibald et al [19,20] described excellent regeneration following median nerve repair in monkeys as by. Its structure also offers biochemical support for nerve regeneration, as it has been showed that collagen is one of extra-cellular matrix (ESM) factors that has been shown to play a significant role in the process of nerve regeneration [6].…”