{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:51:50Z","timestamp":1786121510919,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Diabetic chronic wounds resist healing because persistent bacterial infection, excessive reactive oxygen species (ROS), unresolved pro-inflammatory responses, impaired angiogenesis, and defective tissue remodelling act simultaneously and reinforce one another. We therefore developed an injectable, microenvironment-responsive nanocomposite hydrogel, AP@EM-gel, to target these interconnected pathological processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      AP@EM-gel was constructed from dopamine-grafted alginate (Alg-DA), phenylboronic-acid-modified \u03b5-poly-L-lysine (EPBA), and co-assembled epigallocatechin gallate\u2013metformin nanoparticles (EGCG-MET NPs). Its physicochemical properties, pH\/ROS-responsive drug release, antibacterial and antioxidant activities, cytocompatibility, pro-angiogenic effects, and macrophage-modulating capacity were evaluated\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Therapeutic efficacy was further assessed in a streptozotocin-induced diabetic rat model of Staphylococcus aureus-infected full-thickness wounds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Dynamic boronate-ester crosslinking produced a self-healing and injectable network that released approximately 73% of EGCG and 68% of metformin under combined pH 6.4 and H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      conditions, compared with approximately 38% and 36%, respectively, at pH 7.4. AP@EM-gel achieved antibacterial rates of approximately 93% against\n                      <jats:italic>S. aureus<\/jats:italic>\n                      and 91% against\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      , exhibited broad-spectrum radical-scavenging activity, and showed favourable cyto- and haemocompatibility. It restored VEGF and bFGF expression in oxidatively stressed endothelial cells and promoted macrophage repolarisation toward the reparative M2 phenotype.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , AP@EM-gel produced near-complete wound closure by day 14 and improved bacterial clearance, re-epithelialisation, collagen organisation, angiogenesis, and inflammatory resolution compared with the commercial dressing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>AP@EM-gel simultaneously interrupts infection, oxidative stress, dysregulated macrophage polarisation, and impaired angiogenesis. This pathology-responsive, multi-target hydrogel represents a promising smart dressing for infected diabetic wound regeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1913797","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:29:07Z","timestamp":1786080547000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomaterial-mediated remodelling of the inflammatory microenvironment: a pH\/ROS-responsive EGCG\u2013metformin hydrogel for infected diabetic wound regeneration"],"prefix":"10.3389","volume":"14","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, Sichuan, China"]},{"name":"School of Graduate Studies, Post Graduate Centre, Management and Science University","place":["Shah Alam, Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Fei","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Management and Science University","place":["Shah Alam, Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Wang","sequence":"additional","affiliation":[{"name":"Trauma Medical Center, Department of Orthopaedic Surgery, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Department of Orthopaedics, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Surgical Center, Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxue","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"8278","DOI":"10.3390\/ijms22158278","article-title":"Biofilms in diabetic foot ulcers: impact, risk factors and control strategies","volume":"22","author":"Afonso","year":"2021","journal-title":"Int. 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