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The combination of reactive oxygen species (ROS) scavenging to suppress the oxidative stress damage and macrophage polarization to regenerative M2 phenotype in the MI microenvironment can be desirable for MI treatment. Herein, melanin nanoparticles (MNPs)\/alginate (Alg) hydrogels composed of two marine\u2010derived natural biomaterials, MNPs obtained from cuttlefish ink and alginate extracted from ocean algae, are proposed. Taking advantage of the antioxidant property of MNPs and mechanical support from injectable alginate hydrogels, the MNPs\/Alg hydrogel is explored for cardiac repair by regulating the MI microenvironment. The MNPs\/Alg hydrogel is found to eliminate ROS against oxidative stress injury of cardiomyocytes. More interestingly, the macrophage polarization to regenerative M2 macrophages can be greatly promoted in the presence of MNPs\/Alg hydrogel. An MI rat model is utilized to evaluate the feasibility of the as\u2010prepared MNPs\/Alg hydrogel for cardiac repair in vivo. The antioxidant, anti\u2010inflammatory, and proangiogenesis effects of the hydrogel are investigated in detail. The present study opens up a new way to utilize natural biomaterials for MI treatment and allows to rerecognize the great value of natural biomaterials in cardiac repair.<\/jats:p>","DOI":"10.1002\/advs.202100505","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T01:18:10Z","timestamp":1629422290000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":294,"title":["Natural Melanin\/Alginate Hydrogels Achieve Cardiac Repair through ROS Scavenging and Macrophage Polarization"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3128-407X","authenticated-orcid":false,"given":"Jin","family":"Zhou","sequence":"first","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences  27 Taiping Rd Beijing 100850 P. R. 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