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Growing evidence suggests that impaired axonal regeneration, along with chronic inflammation, impaired angiogenesis, and altered extracellular remodeling, is an important mechanism contributing to the chronic, nonhealing nature of cutaneous wounds. However, the mediators involved and the mechanisms by which they impair wound healing in the presence of hyperglycemia are poorly understood. Peripheral nerves coordinate inflammation, angiogenesis, and extracellular matrix remodeling during repair, and their dysfunction in diabetes disrupts these processes. This review examines how hyperglycemia and oxidative stress impair neuroregeneration ( mainly axonal and nerve regeneration), highlighting the downstream consequences for vascular and structural repair. Particular attention is given to the altered expression of activin A (associated with nerve growth and neural inflammation), TNFRSF10B (associated with neuronal damage and apoptosis, and synaptophysin (a marker of synaptic vesicles and involved in nerve regeneration, particularly in the early stages of axonal regrowth) as representative mediators linking neuronal injury to defective wound healing. By integrating findings across neural, vascular, and inflammatory pathways, this review supports impaired neuronal regeneration as an important contributor to nonhealing diabetic foot ulcer pathogenesis to identify potential molecular targets that may improve healing outcomes.<\/jats:p>","DOI":"10.1007\/s11033-026-11941-5","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:45:31Z","timestamp":1778676331000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Axonal regeneration and hyperglycemia in wound healing: a review on the role of activin A, TNFRSF10B, and Synaptophysin"],"prefix":"10.1007","volume":"53","author":[{"given":"Jaylan","family":"Patel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-2341","authenticated-orcid":false,"given":"Vikrant","family":"Rai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"11941_CR1","unstructured":"Sapra A, Bhandari P (2023) Diabetes. 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