Repair strategies for injured peripheral nerve: Review

Abstract

Compromised functional regains in about half of the patients following surgical nerve repair pose a serious socioeconomic burden to the society. Although surgical strategies such as end-to-end neurorrhaphy, nerve grafting and nerve transfer are widely applied in distal injuries leading to optimal recovery; however in proximal nerve defects functional outcomes remain unsatisfactory. Biomedical engineering approaches unite the efforts of the surgeons, engineers and biologists to develop regeneration facilitating structures such as extracellular matrix based supportive polymers and tubular nerve guidance channels. Such polymeric structures provide neurotrophic support from injured nerve stumps, retard the fibrous tissue infiltration and guide regenerating axons to appropriate targets. The development and application of nerve guidance conduits (NGCs) to treat nerve gap injuries offer clinically relevant and feasible solutions. Enhanced understanding of the nerve regeneration processes and advances in NGCs design, polymers and fabrication strategies have led to developing modern NGCs with superior regeneration-conducive capacities. Current review focuses on the advances in surgical and engineering approaches to treat peripheral nerve injuries. We suggest the incorporation of endothelial cell growth promoting cues and factors into the NGC interior for its possible enhancement effects on the axonal regeneration process that may result in substantial functional outcomes.

Introduction

The ultimate goal of the peripheral nerve repair strategies is to achieve maximal functional regains and shortening the recovery duration. Billions ($150) of dollars are spent annually for the treatment and repair procedures of injured peripheral nerve in the United States [1]. Although mounting evidence suggests the substantial functional regains in mild and moderate nerve injuries through pharmacological, medicinal plant-derivatives and genetic manipulations [[2], [3], [4]], however the application of said strategies is limited in severe nerve trauma. Thus, surgical engineering and combined-therapy approaches are employed in severe nerve injuries to cope the grim situation [1,[5], [6], [7], [8]].

Nerve injuries are classified based on the extent and severity of damage caused [9]. Neuropraxia is the mildest and 1st type of nerve injury and involves no damage to the nerve, except transient changes in myelin and altering the activities of the ion channel to block the nerve conduction. Axonotmesis is the 2nd type of nerve injury and involves the disruption of axonal components of the nerve. Discontinued axons in the distal stump need to be cleared through a process of Wallerian degeneration before the advancements of the regenerating nerve fibers. Neurotemesis is the 3rd and most severe type of nerve injury and involves the complete transection of the nerve trunk, recovery is nearly impossible without surgical intervention [10]. Nerve fiber bundles (fascicles) constitute the nerve trunk, the failure to re-establish the correct fascicle alignment following transection injury is a critical defect leading to poor functional outcomes [11]. It necessitates the advances in microsurgical procedures for effective repair strategies.