{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:17:17Z","timestamp":1785421037181,"version":"3.56.0"},"reference-count":69,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22108225"],"award-info":[{"award-number":["22108225"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["22108225"],"award-info":[{"award-number":["22108225"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Shaanxi Province, China","award":["2021JQ-434"],"award-info":[{"award-number":["2021JQ-434"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Diabetic wounds are characterized by persistent hyperglycemia, excessive ROS accumulation, sustained inflammation, and impaired angiogenesis, yet current treatments remain suboptimal. To address these challenges, we developed a mild heat stimulating and microenvironment reprogramming hydrogel (termed C-4-N) via a green synthetic strategy. L-Arginine (L-Arg) triggered the spontaneous self-polymerization of protocatechuic aldehyde (PA) into poly (protocatechuic aldehyde) (PPA) nanoparticles, onto which ginsenoside Compound K (CK) was subsequently loaded, yielding CK\/L-Arg\/PPA nanoparticles. These nanoparticles were then uniformly embedded into a dynamic disulfide network composed of \u03b1-lipoic acid (LA)-modified chitosan (CS-LA) and 4-arm-PEG-SH under UV irradiation without toxic photo-initiators, forming the C-4-N hydrogel. The C-4-N hydrogel reprogrammed the diabetic wound microenvironment through three synergistic mechanisms, lowering blood glucose and scavenging ROS via the coordinated actions of LA, CK and PPA, promoting M1-to-M2 macrophage polarization via downregulation of pro-inflammatory cytokines (TNF-\u03b1, IL-6) and upregulation of anti-inflammatory cytokines (IL-10, TGF-\u03b21), further amplified by mild photothermal stimulation of 40\u201343 \u00b0C. In a diabetic rat model, the C-4-N hydrogel achieved a near-complete wound closure rate of 99.49 \u00b1 0.10% on day 13 upon mild photothermal stimulation, accompanied by enhanced re-epithelialization, organized collagen deposition, vascular maturation, and systemic glucose regulation. In summary, this green synthesized, mild heat-stimulating hydrogel establishes a synergistic microenvironment reprogramming paradigm for chronic diabetic wound managements.<\/jats:p>","DOI":"10.3390\/gels12060542","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:11:22Z","timestamp":1781709082000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mild Heat Stimulating and Microenvironment Reprogramming Hydrogel for Accelerating Diabetic Wound Healing"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6797-5716","authenticated-orcid":false,"given":"Xueting","family":"Xiao","sequence":"first","affiliation":[{"name":"Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"},{"name":"Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-143X","authenticated-orcid":false,"given":"Yannan","family":"Liu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"},{"name":"Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"},{"name":"Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lebin","family":"Wang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"},{"name":"Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirui","family":"Hu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"},{"name":"Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinliang","family":"Xing","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"},{"name":"Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Ding","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"},{"name":"Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xurun","family":"Wang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"},{"name":"Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"},{"name":"Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of 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