AUTHOR=Foy Christian A. , Kuffler Damien P. TITLE=Limitations to clinically restoring meaningful peripheral nerve function across gaps and overcoming them JOURNAL=Experimental Biology and Medicine VOLUME=Volume 250 - 2025 YEAR=2025 URL=https://www.ebm-journal.org/journals/experimental-biology-and-medicine/articles/10.3389/ebm.2025.10566 DOI=10.3389/ebm.2025.10566 ISSN=1535-3699 ABSTRACT=Clinically, reliably restoring meaningful peripheral sensory and motor nerve function across peripheral nerve gaps is limited. Thus, although autografts are the clinical “gold standard” repair technique for bridging nerve gaps, even under relatively good conditions, <50% of patients recover meaningful function. Due to this low recovery rate, many patients are not even provided repair surgery and, consequently, suffer permanent loss of function. This paper examines intrinsic and extrinsic changes associated with injured neurons and Schwann cells that reduce the extent of axon regeneration and recovery. It also examines how these changes can be reversed, leading to enhanced regeneration and recovery. It next examines the efficacy of platelet-rich plasma (PRP) in promoting axon regeneration and two novel techniques involving bridging nerve gaps with an autograft within a platelet-rich (PRP) collagen tube or only a PRP-filled collagen tube, which induce meaningful recovery under conditions where autografts alone are not effective. Finally, it looks at potential mechanisms by which platelet-released factors may enhance axon regeneration and recovery. This review shows that although there are many limitations to restoring meaningful function following peripheral nerve trauma, there are a number of ways these can be overcome. Presently, the most promising techniques involve using PRP.