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Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN\u2010SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non\u2010dynamic photo\u2010crosslinked bonds respectively. The single network hydrogel before photo\u2010crosslinking exhibits excellent injectability and thus can be printed and photo\u2010crosslinked in situ to form double network hydrogels. DN\u2010SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an \u201coperando\u201d comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN\u2010SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN\u2010DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds.<\/jats:p>","DOI":"10.1002\/advs.202310162","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T09:43:10Z","timestamp":1712828590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Spermidine\u2010Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ"],"prefix":"10.1002","volume":"11","author":[{"given":"Qianqian","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Bionic Engineering (Ministry of Education) Jilin University  Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runjiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bionic 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