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Exogenous delivery of nitric oxide (NO) to the infarcted myocardium has proven to be an effective strategy for treating MI due to the multiple physiological functions of NO. However, reperfusion of blood flow to the ischemic tissues is accompanied by the overproduction of toxic reactive oxygen species (ROS), which can further exacerbate tissue damage and compromise the therapeutic efficacy. Here, an injectable hydrogel is synthesized from the chitosan modified by boronate\u2010protected diazeniumdiolate (CS\u2010B\u2010NO) that can release NO in response to ROS stimulation and thereby modulate ROS\/NO disequilibrium after ischemia\/reperfusion (I\/R) injury. Furthermore, administration of CS\u2010B\u2010NO efficiently attenuated cardiac damage and adverse cardiac remodeling, promoted repair of the heart, and ameliorated cardiac function, unlike a hydrogel that only released NO, in a mouse model of myocardial I\/R injury. Mechanistically, regulation of the ROS\/NO balance activated the antioxidant defense system and protected against oxidative stress induced by I\/R injury via adaptive regulation of the Nrf2\u2010Keap1 pathway. Inflammation is then reduced by inhibition of the activation of NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B signaling. Collectively, these results show that this dual\u2010function hydrogel may be a promising candidate for the protection of tissues and organs after I\/R injury.\n                  <\/jats:p>","DOI":"10.1002\/advs.202105408","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T08:54:19Z","timestamp":1648025659000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":159,"title":["An Injectable Dual\u2010Function Hydrogel Protects Against Myocardial Ischemia\/Reperfusion Injury by Modulating ROS\/NO Disequilibrium"],"prefix":"10.1002","volume":"9","author":[{"given":"Tian","family":"Hao","sequence":"first","affiliation":[{"name":"State key Laboratory of Medicinal Chemical Biology Haihe Laboratory of Sustainable Chemical Transformations Key Laboratory of Bioactive Materials (Ministry of Education) Frontiers Science Center for Cell Responses College of Life Sciences Nankai University  Tianjin 300071 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