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Here, we developed an extracellular matrix-mimicking dressing, termed ANM, that modulates arginine utilization within the diabetic wound microenvironment to re-establish the spatiotemporal coordination of healing. ANM was in situ fabricated by hand-held electrospinning using a rationally designed arginine- and norvaline-based poly(ester amide), yielding a conformable and breathable nanofibrous dressing. Its porous and hydrolyzable structure enabled moisture- and enzyme-responsive degradation, allowing sustained release of arginine- and norvaline-containing degradants. These bioactive degradants cooperatively modulated macrophage phenotypic transitions, initially promoting a timely proinflammatory response, followed by a spontaneous shift toward a pro-reparative state, thereby restoring the temporally sequenced inflammatory program in diabetic wounds. Meanwhile, ANM locally upregulated inducible nitric oxide synthase (iNOS) and arginase-1 in the peri-wound epidermis, spatially promoting the proliferation and differentiation of epidermal keratinocytes and accelerating re-epithelialization. In contrast to commercial dressings that failed to support healing and even led to progressive deterioration over 21 days, ANM significantly promoted collagen deposition and angiogenesis and accelerated wound closure in db\/db mice by 14 days. This work offers a promising strategy for treating chronic nonhealing wounds through spatiotemporal metabolic modulation.<\/jats:p>","DOI":"10.1021\/acsnano.6c07848","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:01:22Z","timestamp":1790442082000},"page":"27092-27107","source":"Crossref","is-referenced-by-count":0,"title":["Nanofibrous\nPoly(amino acid ester) Dressing for Promoting\nDiabetic Wound Healing via Spatiotemporal Coordination of Immunomodulation\nand Tissue Regeneration"],"prefix":"10.1021","volume":"20","author":[{"given":"Li","family":"Ma","sequence":"first","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]},{"name":"The Hong Kong Polytechnic University , , ,","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Feng","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijun","family":"Li","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangrui","family":"Du","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]},{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hexin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]},{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8850-2184","authenticated-orcid":true,"given":"Ying","family":"Ji","sequence":"additional","affiliation":[{"name":"The Hong Kong Polytechnic University , , ,","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0414-4397","authenticated-orcid":true,"given":"Kaikai","family":"Ma","sequence":"additional","affiliation":[{"name":"The Hong Kong Polytechnic University , , ,","place":["Hong Kong, China"]},{"name":"The Hong Kong Polytechnic University , , ,","place":["Hong Kong, China"]},{"name":"The Hong Kong Polytechnic University , , ,","place":["Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Shuai","sequence":"additional","affiliation":[{"name":"West China Hospital of Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-4668","authenticated-orcid":true,"given":"Gongyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]},{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]},{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"2026101310083904200_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123780","article-title":"Framework nucleic acid-based hydrogel\nfor sequential immune regulation and endogenous TGF-beta1 capture\nin wound healing","volume":"327","author":"Yin","year":"2026","journal-title":"Biomaterials"},{"key":"2026101310083904200_cit2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123569","article-title":"Programmed\ntemporal modulation by using a magnetoelectric\nwound dressing for ultra-fast early-stage wound healing","volume":"325","author":"Zhao","year":"2026","journal-title":"Biomaterials"},{"key":"2026101310083904200_cit3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2024.153748","article-title":"Smart and\nbioactive electrospun dressing for accelerating\nwound healing","volume":"496","author":"Xu","year":"2024","journal-title":"Chem. 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Mater. Chem.\nB"},{"key":"2026101310083904200_cit19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00532","article-title":"Metabolism\nvia arginase or nitric oxide synthase: Two competing arginine pathways\nin macrophages","volume":"5","author":"Rath","year":"2014","journal-title":"Front. Immunol."},{"issue":"8","key":"2026101310083904200_cit20","doi-asserted-by":"publisher","first-page":"9640","DOI":"10.1021\/acsami.3c13072","article-title":"Arginine-nanoenzyme\nwith timely angiogenesis for promoting diabetic wound healing","volume":"16","author":"Yang","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2026101310083904200_cit21","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.773866","article-title":"Arginase signalling\nas a key player in chronic wound pathophysiology and healing","volume":"8","author":"Szondi","year":"2021","journal-title":"Front. Mol. 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Dermatol."},{"issue":"1","key":"2026101310083904200_cit25","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01425-x","article-title":"High glucose-induced STING activation\ninhibits diabetic wound healing through promoting M1 polarization\nof macrophages","volume":"9","author":"Geng","year":"2023","journal-title":"Cell Death Discovery"},{"issue":"1","key":"2026101310083904200_cit26","doi-asserted-by":"publisher","first-page":"H342","DOI":"10.1152\/ajpheart.1998.274.1.H342","article-title":"Arginase modulates\nnitric oxide production\nin activated macrophages","volume":"274","author":"Chang","year":"1998","journal-title":"Am. J. 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