Nerve recovery from treatment with a vascularized nerve graft compared to an autologous non-vascularized nerve graft in animal models: A systematic review and meta-analysis.

Berend O Broeren,Caroline A Hundepool,Liron S Duraku,Tim De Jong,Erik T Walbeehm,J Michiel Zuidam,Carlijn R Hooijmans,Leila Harhaus

doi:10.1371/journal.pone.0252250

Abstract

Treatment of nerve injuries proves to be a worldwide clinical challenge. Vascularized nerve grafts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous non-vascularized nerve graft. However, there is no adequate clinical evidence for the beneficial effect of vascularized nerve grafts and they are still disputed in clinical practice. To systematically review whether vascularized nerve grafts give a superior nerve recovery compared to non-vascularized nerve autografts regarding histological and electrophysiological outcomes in animal models. PubMed and Embase were systematically searched. The inclusion criteria were as follows: 1) the study was an original full paper which presented unique data; 2) a clear comparison between a vascularized and a non-vascularized autologous nerve transfer was made; 3) the population study were animals of all genders and ages. A standardized mean difference and 95% confidence intervals for each comparison was calculated to estimate the overall effect. Subgroup analyses were conducted on graft length, species and time frames. Fourteen articles were included in this review and all were included in the meta-analyses. A vascularized nerve graft resulted in a significantly larger diameter, higher nerve conduction velocity and axonal count compared to an autologous non-vascularized nerve graft. However, during sensitivity analysis the effect on axonal count disappeared. No significant difference was observed in muscle weight. Treating a nerve gap with a vascularized graft results in superior nerve recovery compared to non-vascularized nerve autografts in terms of axon count, diameter and nerve conduction velocity. No difference in muscle weight was seen. However, this conclusion needs to be taken with some caution due to the inherent limitations of this meta-analysis. We recommend future studies to be performed under conditions more closely resembling human circumstances and to use long nerve defects.

Highlights

Treatment of nerve injuries proves to be a worldwide clinical challenge
Fourteen articles were included in this review and all were included in the meta-analyses
No significant difference was observed in muscle weight

Summary

Introduction

Treatment of nerve injuries proves to be a worldwide clinical challenge. Even though adequately treated, affected patients may suffer from chronic pain or lasting motor and sensory deficits [1]. For clinical situations in which it is necessary to bridge a nerve gap and when a tensionless coaptation is not possible, the current gold standard is an autologous non-vascularized (conventional) nerve graft. Treatment with a nerve graft always has a worse nerve recovery compared to primary coaptation, due to two anastomosis sides which increases the surface that needs to regenerate, ischemia of the graft and frequently a poor wound bed [2]. Grafted nerves need considerable energy to regenerate and to maintain function. This energy is delivered by the intraneural vascular system, which is connected to extrinsic vessels. Vascularized nerve grafts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous non-vascularized nerve graft. There is no adequate clinical evidence for the beneficial effect of vascularized nerve grafts and they are still disputed in clinical practice

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Conclusion