From Bench to Bedside: Recent Progress and Challenges in Translating Bioengineered Nerve Grafts for Peripheral Nerve Repair to Human Trials—A Comprehensive Scoping Review

Abstract

Peripheral nerve injuries (PNIs) can lead to long-term disability and impose a substantial economic burden. To overcome limitations of current gold-standard reconstruction, tissue-engineered nerve grafts (TENGs) have been developed and demonstrate promising results in experimental models. Our group detailed the most promising TENGs in a 2018 review article, but the extent of translation to clinical trials is unclear. The objective of this scoping literature review is to provide an update on clinical translation and a brief bibliometric analysis of progress through the first quarter of the 21st century.

A comprehensive literature search for PNI and tissue engineering was conducted across multiple databases in November 2025 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Articles evaluating PNI reconstruction with TENGs in human participants were included. Articles published since 2000 were categorized, and yearly publications were analyzed.

Twenty-nine of 754 screened articles met inclusion criteria. Since 2017, most articles evaluated bioengineered conduits (n = 16) and acellular nerve grafts (ANGs; n = 9). Only three publications compared outcomes between various TENGs. There were no studies identified that evaluated ANG modification (cellularization or enriching with neurotrophic factors) nor conduit modification (incorporation of extracellular matrix proteins or elongated dorsal root ganglion neurons). Visualization of yearly publications in the field does not demonstrate the warranted increase in clinical trials.

Our comprehensive literature search reveals a persistent substantial gap between promising experimental results and rigorous clinical trials of TENGs for reconstructing PNIs. Challenges in bridging this gap are discussed, and suggestions to overcome them are provided.