Peer-reviewed veterinary case report
Structural Features of Nerve Guidance Conduits and Scaffolds in Preventing Axonal Misdirection: A Systematic Review of Retrograde Tracing Studies.
By Mićić A et al.·2026·Faculty of Medicine·View original on Europe PMC →
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Plain-English summary
This study looked at how different designs of nerve guidance conduits (NGCs) and nerve scaffolds (NSCs) might help in repairing damaged nerves by preventing axons (nerve fibers) from going the wrong way. Researchers reviewed many studies involving animals that had their nerves cut and then repaired using either their own tissue (autografts) or artificial materials. They found that while structured designs of NGCs and NSCs seemed to work better than simpler designs, the overall evidence was weak and inconsistent. Many studies did not report on how well they prevented axonal misdirection, making it hard to draw solid conclusions. In the end, the study suggests that while structured designs might be better, there's not enough reliable evidence to say any one design is the best choice for nerve repair.
Abstract
<b>Background:</b> Axonal misdirection remains a major limitation in peripheral nerve repair. While nerve guidance conduits (NGCs) and nerve scaffolds (NSCs) have advanced structurally, it is unclear whether these designs effectively reduce misdirection compared to autografts (ANGs). This systematic review evaluates the impact of NGC and NSC structural features on axonal dispersion and reinnervation accuracy using retrograde tracing animal models. <b>Methods:</b> A systematic search was performed through Medline (PubMed), Scopus (EBSCOhost), and the Cochrane Library from inception to December 2024. Eligible studies included mammalian in vivo models of peripheral nerve transection repaired by direct coaptation, autografts, or artificial conduits and assessed with retrograde axonal tracing. Data on neurons labeling, innervation accuracy, and histomorphometric parameters were extracted, and misdirection rates were calculated. Risk of bias was assessed using the SYRCLE tool. Due to heterogeneity, data were synthesized narratively following the SWiM framework. <b>Results:</b> Out of 4043 records identified through database searching and 37 through citation searching, 19 studies (49 experimental groups) met the inclusion criteria. Motoneuron counts were consistently reported across all arms, but no outcome assessing axonal misdirection was reported in more than half. Structured designs resulted in outcomes more closely aligned with ANG repair, while unstructured generally underperformed, and certainty of evidence was very low. <b>Discussion:</b> The evidence in this study was limited by high risk of bias, substantial inconsistency across heterogeneous study designs and outcomes, and imprecision from small animal models with sparse outcome measures. Despite the trend for structured designs to improve over basic hollow designs, current evidence does not support any structure as superior. Future research should be more standardized to provide reliable knowledge translational into clinical practice.
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Search related cases →Original publication on Europe PMC: https://europepmc.org/article/MED/41749759