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An effective paradigm for heart repair in rodent and large animal models is the transplantation of human induced pluripotent stem cell\u2010derived cardiomyocytes (hiPSC\u2010CMs). Despite this, the functional and phenotypical immaturity of 2D\u2010cultured hiPSC\u2010CMs, particularly their low electrical integration, poses a caveat for clinical translation. In this study, a supramolecular assembly of a glycopeptide containing a cell adhesion motif\u2010RGD, and saccharide\u2010glucose (Bio\u2010Gluc\u2010RGD) is designed to enable the 3D spheroid formation of hiPSC\u2010CMs, promoting cell\u2010cell and cell\u2010matrix interactions that occur during spontaneous morphogenesis. HiPSC\u2010CMs in spheroids are prone to be phenotypically mature and developed robust gap junctions via activation of the integrin\/ILK\/p\u2010AKT\/Gata4 pathway. Monodispersed hiPSC\u2010CMs encapsulated in the Bio\u2010Gluc\u2010RGD hydrogel are more likely to form aggregates and, therefore, survive in the infarcted myocardium of mice, accompanied by more robust gap junction formation in the transplanted cells, and hiPSC\u2010CMs delivered with the hydrogels also displayed angiogenic effect and anti\u2010apoptosis capacity in the peri\u2010infarct area, enhancing their overall therapeutic efficacy in myocardial infarction. Collectively, the findings illustrate a novel concept for modulating hiPSC\u2010CM maturation by spheroid induction, which has the potential for post\u2010MI heart regeneration.<\/jats:p>","DOI":"10.1002\/adhm.202300696","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T11:34:23Z","timestamp":1687260863000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Supramolecular Assemblies of Glycopeptides Enhance Gap Junction Maturation of Human Induced Pluripotent Stem Cell\u2010Derived Cardiomyocytes via Inducing Spheroids Formation to Optimize Cardiac Repair"],"prefix":"10.1002","volume":"12","author":[{"given":"Hekai","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease Department of Cardiology and Laboratory of Heart Center Sino\u2010Japanese Cooperation Platform for Translational 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