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A tri\u2010cross\u2010linked inflammatory microenvironment\u2010responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment\u2010responsive hydrogel (OD\u2010PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano\u2010fillers into the hydrogel results in extra cross\u2010linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)\/pH dual responsive hydrogel with a triple\u2010network is achieved. The hydrogel has injectable, self\u2010healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli\u2010responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH\u2010regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K\/AKT\/NF\u2010\u03baB and MAPK pathways, exerting anti\u2010inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple\u2010network structure provides an effective strategy to treat IDs, holding great promise in clinical application.\n                  <\/jats:p>","DOI":"10.1002\/advs.202303167","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T00:35:44Z","timestamp":1695429344000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["Triple Cross\u2010linked Dynamic Responsive Hydrogel Loaded with Selenium Nanoparticles for Modulating the Inflammatory Microenvironment via PI3K\/Akt\/NF\u2010\u03baB and MAPK Signaling Pathways"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0270-1305","authenticated-orcid":false,"given":"Shuangqing","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of 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