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Recent advances have enabled the development of multifunctional hydrogels that combine biophysical and biochemical cues\u2014including conductive materials, bioactive molecules, and exosomes\u2014to create healing microenvironments that promote nerve growth, angiogenesis, and tissue repair, particularly in challenging conditions such as diabetic ulcers and chronic wounds. This review examines the molecular mechanisms underlying neural regulation of wound healing, focusing on sensory neuron-derived factors, neuro-immune crosstalk, neurovascular integration, and the emerging role of neurogenic exosomes as central signaling hubs. Furthermore, design principles for hydrogel materials\u2014including natural, synthetic, and composite systems\u2014are explored alongside smart responsive hydrogels that adapt to dynamic wound environments, thereby enabling controlled therapeutic delivery. Current trends integrating wearable bioelectronics, artificial intelligence (AI), and bioengineered scaffolds are discussed in the context of real-time monitoring and personalized therapy. While neurogenic hydrogels show significant promise for clinical translation, their development requires rigorous preclinical validation and well-designed human trials. Beyond skin regeneration, these materials hold potential for nerve repair, bone healing, and cardiac tissue engineering, highlighting their versatility as therapeutic solutions across diverse physiological systems. Future efforts should focus on leveraging AI to optimize hydrogel formulations, advancing stem cell-based therapies, and establishing standardized metrics for treatment efficacy.<\/jats:p>","DOI":"10.3389\/fcell.2026.1797417","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:17:27Z","timestamp":1779949047000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Hydrogel-based neural engineering for skin wound healing"],"prefix":"10.3389","volume":"14","author":[{"given":"Yibo","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Wound Repair, Plastic and Reconstructive Microsurgery, China-Japan Union Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangzhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Wound Repair, Plastic and Reconstructive Microsurgery, China-Japan Union Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"B168","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1007\/s12035-017-0390-0","article-title":"Surgical denervation of specific cutaneous nerves impedes excisional wound healing of small animal ear pinnae","volume":"55","author":"Alapure","year":"2018","journal-title":"Mol. 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