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However, achieving secure adhesion onto the wet beating heart and local regulation of pathological microenvironment remains challenging. Herein, a dough\u2010kneading\u2010inspired design of hydrogel adhesive cardiac patch is reported, aiming to improve the strength of prevalent powder\u2010formed patch and retain wet adhesion. In mimicking the polysaccharide and protein components of natural flour, methacrylated polyglutamic acid (PGAMA) is electrostatically interacted with hydroxypropyl chitosan (HPCS) to form PGAMA\/HPCS coacervate hydrogel. The PGAMA\/HPCS hydrogel is freeze\u2010dried and ground into powders, which are further rehydrated with two aqueous solutions of functional drug, 3\u2010acrylamido phenylboronic acid (APBA)\/rutin (Rt) complexes for protecting the myocardium from advanced glycation end product (AGEs) injury by reactive oxygen species (ROS) \u2010responsive Rt release, and hypoxanthine\u2010loaded methacrylated hyaluronic acid (HAMA) nanogels for enhancing macrophage targeting ability to regulate glycometabolism for combating inflammation. The rehydrated powders bearing APBA\/Rt complexes and HAMA\u2010hypoxanthine nanogels are repeatedly kneaded into a dough\u2010like gel, which is further subjected to thermal\u2010initiated crosslinking to form a stabilized and sticky patch. This biofunctional patch is applied onto the rats\u2019 infarcted myocardium, and the outcomes at 28 days post\u2010surgery indicate efficient restoration of cardiac functions and attenuation of cardiac fibrosis.<\/jats:p>","DOI":"10.1002\/adhm.202303685","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T16:09:30Z","timestamp":1708618170000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Dough\u2010Kneading\u2010Inspired Design of an Adhesive Cardiac Patch to Attenuate Cardiac Fibrosis and Improve Cardiac Function via Regulating Glycometabolism"],"prefix":"10.1002","volume":"13","author":[{"given":"Yage","family":"Sun","sequence":"first","affiliation":[{"name":"School of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional Materials Tianjin University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional Materials Tianjin University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongfeng","family":"Nie","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional Materials Tianjin University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional Materials Tianjin University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional Materials Tianjin University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional Materials Tianjin University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7936-7929","authenticated-orcid":false,"given":"Wenguang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional Materials Tianjin University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2021.101227"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.044125"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202214468"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-017-0157-y"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acvd.2020.01.002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.07.029"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2023.101861"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe8739"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2219024120"},{"key":"e_1_2_7_10_1","volume":"31","author":"Peng X.","year":"2021","journal-title":"Adv. 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