Advancing Peripheral Nerve Regeneration (Nerve SPACE 2025)

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Peripheral nerve injuries remain a major clinical challenge due to slow axonal regeneration, rapid Wallerian degeneration (WD), and degeneration of target organs prior to reinnervation. Where are we now? Strategies to enhance regeneration can be broadly divided into three categories: preventing or delaying WD, speeding up axonal regeneration, and improving the molecular environment at the injury site. Approaches to delay WD include polyethylene glycol-mediated axonal fusion, which may restore early axonal continuity and conduction, and inhibition of sterile alpha and TIR motif-containing 1, the central executioner of WD, with small-molecule inhibitors now in clinical trials. Methods to accelerate axon regrowth include brief intraoperative electrical stimulation, which activates regeneration-associated gene programs and improves motor and sensory recovery in both preclinical and early clinical studies, and pharmacologic augmentation with 4-aminopyridine, which enhances conduction across demyelinated fibers and promotes remyelination. Where do we need to go? Optimizing the local microenvironment through cellular and molecular adjuncts, including mesenchymal stem cells, Schwann cells, exosomes, surgical angiogenesis, and local delivery of neuroregenerative drugs such as FK506, has also shown promise in experimental models. Across all approaches, progress is hindered by heterogeneo

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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