Safety and efficacy of an injectable nerve-specific hydrogel in a rodent crush injury model.

2021 
INTRODUCTION/AIMS While the peripheral nervous system has the inherent ability to recover following injury, results are often unsatisfactory, resulting in permanent functional deficits and disability. Therefore, methods that enhance regeneration are of significant interest. The present study investigates an injectable nerve-tissue-specific hydrogel as a biomaterial for nerve regeneration in a rat nerve crush model. METHODS Nerve specific hydrogels were injected into the subepineurial space in uninjured and crushed sciatic nerves of rats to assess safety and efficacy, respectively. The animals were followed longitudinally for 12 weeks using sciatic functional index and kinematic measures. At 12 weeks, electrophysiologic examination was performed, followed by harvest of the nerve and muscle tissues for histologic assessment. RESULTS No differences in sciatic functional index, kinematic function, or axon counts were noted when the hydrogel was injected into a healthy nerve. A slight reduction in muscle fiber diameter was observed in the hydrogel-injected animals, but overall muscle area and kinematic function were not affected. Following nerve crush, multiple modest improvements were observed in sciatic functional index and kinematic function with an earlier return to normal function observed in hydrogel treated animals as compared to untreated controls. While no improvements in supramaximal compound motor action potential were observed in hydrogel treated animals, increased axon counts were observed on histologic assessment. DISCUSSION These improvements in functional and histologic outcomes in a rapidly and fully recovering model suggest that injection of a nerve specific hydrogel is safe and has the potential to improve outcomes following nerve injury. This article is protected by copyright. All rights reserved.
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