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While recent advances include microcapped microneedle patches and the TIMED platform, these systems face limitations in customizability, release duration, and fabrication simplicity. Here, this study reports a programmable microneedle platform that mimics the temporal paracrine signaling logic of stem cell therapy by generating phase\u2010biased, kinetically staggered, and partially overlapping availability of TGF\u2010\u03b2, IGF\u20101, and VEGF through a tris(2,2'\u2010bipyridyl)dichlororuthenium(II) hexahydrate\/sodium persulfate (Ru\/SPS)\u2010modulated tyramine crosslinked hydrogel network. This system demonstrates enhanced advantages, including straightforward tunability of release kinetics via Ru\/SPS concentration adjustment, extended release duration up to \u223c60 days, and a simplified fabrication process. In myocardial infarction models, this stem cell\u2010inspired temporal release promoted anti\u2010inflammatory, anti\u2010apoptotic, and pro\u2010angiogenic responses, restoring ventricular function. Direct schedule\u2010control experiments further showed that the tested TGF\u2010\u03b2\/IGF\u20101\/VEGF program outperformed 7\u2010 and 28\u2010 day simultaneous\u2010window delivery and two order\u2010swapped 7\/14\/28\u2010day programs across functional, structural, angiogenic, and cardiomyocyte\u2010proliferation readouts. This strategy establishes a generalizable framework for engineering time\u2010coded therapeutic materials that emulate biological signaling programs.<\/jats:p>","DOI":"10.1002\/advs.77101","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:50:03Z","timestamp":1787050203000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Programmable Paracrine\u2010Mimetic Microneedle System for Temporal Regulation of Cardiac Repair"],"prefix":"10.1002","author":[{"given":"Yichen","family":"Dai","sequence":"first","affiliation":[{"name":"School of Medicine The Chinese University of Hong Kong  Shenzhen Guangdong China"},{"name":"CUHKSZ\u2010Dalian Practical Biotechnology Joint Laboratory for Biomedicine The Chinese University of Hong Kong  Shenzhen Guangdong 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