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Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell\u2010derived factor\u20101 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue\u2010adhesive silk\u2010based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by \u224830% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by \u224810% and 20%, respectively, with a \u224825% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy.<\/jats:p>","DOI":"10.1002\/smll.202312261","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T09:41:42Z","timestamp":1715420502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Injectable Self\u2010Oxygenating Cardio\u2010Protective and Tissue Adhesive Silk\u2010Based Hydrogel for Alleviating Ischemia After Mi Injury"],"prefix":"10.1002","volume":"20","author":[{"given":"Shabir","family":"Hassan","sequence":"first","affiliation":[{"name":"Division of Engineering in Medicine, Brigham and Women's Hospital, Department of Medicine Harvard Medical School  65 Landsdowne St Cambridge 02139 United\u00a0States"},{"name":"Department of Biological Sciences Khalifa University  Shakhbout Bin Sultan St Abu Dhabi 127788 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