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Inspired by these natural phenomena and design principles, the fabrication of an engineered nanofibrous, extracellular matrix (ECM) mimicking self\u2010assembling peptide hydrogel is reported. This hydrogel integrates a neuroregenerative motif (NAV) derived from Activity Dependent Neuroprotective Protein (ADNP) with a self\u2010assembling motif (K\n                    <jats:sub>2<\/jats:sub>\n                    [SL]\n                    <jats:sub>6<\/jats:sub>\n                    K\n                    <jats:sub>2<\/jats:sub>\n                    ) to enhance neurite outgrowth. Interestingly, it is observed that this engineered hydrogel displays a network of prominent, directed filament\u2010like structures. Remarkably, it supports and promotes the directional differentiation and alignment of stem cells into neuronal lineages. Motivated by this result, its therapeutic potential is evaluated in a rat model of sciatic nerve injury, where guided nerve regeneration is essential. The hydrogel is applied as a nerve guidance matrix, leading to structural repair and significant functional recovery of the injured nerve within two weeks. These findings are further supported by behavioral assessments, histological analysis, and evaluation of gastrocnemius muscle reinnervation. Overall, the results demonstrate that this engineered peptide hydrogel effectively promotes nerve regeneration and functional restoration, highlighting its promise as a therapeutic platform for peripheral nerve injury.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202503429","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T11:53:47Z","timestamp":1760097227000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Engineered Neuro\u2010Regenerative Peptide Hydrogel for Directed Neural Lineage Reprograming and Regeneration of Sciatic Nerve Injury"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3801-549X","authenticated-orcid":false,"given":"Shubham","family":"Garg","sequence":"first","affiliation":[{"name":"Department of Bioscience &amp; Bioengineering Indian Institute of Technology  NH 62, Surpura Bypass Road, Karwar Jodhpur Rajasthan 342037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniket","family":"Jana","sequence":"additional","affiliation":[{"name":"Smart Healthcare Interdisciplinary Research Platform Indian Institute of Technology Jodhpur  Karwar Jodhpur Rajasthan 342037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanju","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Bioscience &amp; Bioengineering Indian Institute of Technology  NH 62, Surpura Bypass Road, Karwar Jodhpur Rajasthan 342037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Umar","family":"Arshi","sequence":"additional","affiliation":[{"name":"Department of Bioscience &amp; Bioengineering Indian Institute of Technology  NH 62, Surpura Bypass Road, Karwar Jodhpur Rajasthan 342037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-6505","authenticated-orcid":false,"given":"Juhee","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Bioscience &amp; Bioengineering Indian Institute of Technology  NH 62, Surpura Bypass Road, Karwar Jodhpur Rajasthan 342037 India"},{"name":"Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division CSIR\u2010Indian Institute of Chemical Biology  Raja S. 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