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Although conventional free silver nanoparticles (AgNPs) possess broad-spectrum antimicrobial activity, their inherent tendency to aggregate and inactivate, as well as its high cytotoxicity limits their clinical application. Moreover, a single bactericidal strategy is insufficient to completely reverse the complex pathogenic microenvironment of the wound. To address these challenges, this study developed a dual-polyphenol biomimetic extracellular matrix (ECM) composite hydrogel with matrix metalloproteinase-9 (MMP-9) and pH-responsive properties, aimed at achieving spatiotemporal precision intervention and active microenvironment remodeling in diabetic wounds. This system employs caffeic acid-modified gelatin and dopamine-modified sodium alginate as a dynamically cross-linked scaffold, incorporated with AgNPs-anchored zinc\u2013aluminum layered double hydroxide (ZnAl-LDH@Ag), that can precisely match the dynamic pathological evolution of the wound. The hydrogel exhibits pathology-adaptive behavior through two complementary mechanisms: gradual MMP-9-mediated remodeling of the gelatin network and infection-associated pH-responsive ion release. MMP-9-mediated degradation enables sustained exposure of ZnAl-LDH@Ag and prolonged matrix remodeling, whereas the acidic microenvironment promotes on-demand release of antibacterial Ag+ and regenerative Zn2+ ions. Additionally, polyphenol moieties provide antioxidant and anti-inflammatory regulation during wound healing. By integrating two-dimensional inorganic layered materials (ZnAl-LDH) with conventional metal nanocrystals (AgNPs), this strategy resolves the clinical paradox in silver-based therapies: the difficulty of balancing high bactericidal activity with low cytotoxicity. In summary, this pathology-driven therapeutic platform enables multimodal synergistic therapy for antioxidant protection, infection control, and tissue regeneration, providing a theoretical foundation and design perspectives for the development of advanced dressings for complex chronic wounds.<\/jats:p>","DOI":"10.1021\/acsami.6c12232","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T10:01:40Z","timestamp":1791799300000},"source":"Crossref","is-referenced-by-count":0,"title":["A Pathology-Responsive Hydrogel with On-Demand Ion Release for Microenvironment Remodeling and Diabetic Wound Regeneration"],"prefix":"10.1021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3547-9563","authenticated-orcid":true,"given":"Jiawei","family":"Cui","sequence":"first","affiliation":[{"name":"Southwest Jiaotong University , , ,","place":["Chengdu, China, 610031"]},{"name":"Southwest Jiaotong University , , ,","place":["Chengdu, China, 610031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueming","family":"Luo","sequence":"additional","affiliation":[{"name":"Southwest Jiaotong University , , ,","place":["Chengdu, China, 610031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhi","family":"Kuang","sequence":"additional","affiliation":[{"name":"Southwest Jiaotong University , , ,","place":["Chengdu, China, 610031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Southwest Jiaotong University , , ,","place":["Chengdu, China, 610031"]},{"name":"The Third People\u2019s Hospital of Chengdu , ,","place":["Chengdu, China, 610031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rifang","family":"Luo","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5204-6684","authenticated-orcid":true,"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Southwest Jiaotong University , , ,","place":["Chengdu, China, 610031"]},{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"Southwest Jiaotong University , , ,","place":["Chengdu, China, 610031"]},{"name":"Southwest Jiaotong University , , ,","place":["Chengdu, China, 610031"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"issue":"1","key":"2026101206013012300_cit1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45101-9","article-title":"Programmed microalgae-gel promotes chronic wound healing in diabetes","volume":"15","author":"Kang","year":"2024","journal-title":"Nat. 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