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Current therapies mainly deal with bacteria elimination, but directly addressing the over\u2010accumulated multiple inflammatory mediators in the periodontal microenvironment still remains a substantial challenge for regenerative periodontitis treatment. Herein, inspired by blood coagulation, an off\u2010the\u2010shelf artificial blood clot hydrogel encapsulated with platelet\u2010rich plasma (PRP) is reported to mitigate the deteriorative inflammatory environment in periodontitis. The hydrogel (CCS\u2010RSF@PRP) with a hierarchical fibers\u2010interwoven network structure, in which the activated platelets are enriched, is structurally similar to the native blood clot. Functionally, in addition to the function of enriching and releasing growth factors, CCS\u2010RSF@PRP can remarkably scavenge reactive oxygen species (ROS), neutralize endotoxin lipopolysaccharide (LPS), and proinflammatory cytokines (TNF\u2010\u03b1, IFN\u2010\u03b3 and IL\u20101\u03b2), inhibit M1 macrophage polarization and induce M2 macrophage polarization, thus blocking the chronic inflammatory feedback loop in the periodontitis. In rat periodontitis model, CCS\u2010RSF@PRP hydrogel significantly expedits the repair of periodontium by normalizing the periodontal immune\u2010environment. The work highlights the importance of local immunomodulation in the treatment of periodontitis, and the engineered PRP\u2010derived hydrogel can mimic and expand the structure and function of native blood clot, holding great promise in treating chronic inflammatory diseases.<\/jats:p>","DOI":"10.1002\/advs.202504106","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T07:32:55Z","timestamp":1748417575000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["An Off\u2010the\u2010Shelf Artificial Blood Clot Hydrogel Neutralizing Multiple Proinflammatory Mediators for Pro\u2010Regenerative Periodontitis Treatment"],"prefix":"10.1002","volume":"12","author":[{"given":"Yini","family":"Huangfu","sequence":"first","affiliation":[{"name":"Department of Polymer Science and Engineering Key Laboratory of Systems Bioengineering (Ministry of Education) School of Chemical Engineering and Technology Tianjin University  Tianjin 300072 P. 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