{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:43:10Z","timestamp":1787067790363,"version":"build-2736575974"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>Impaired microcirculation and insufficient angiogenesis critically limit functional recovery after myocardial infarction (MI), yet effective strategies for localized and sustained vascular regeneration remain lacking. Here, we develop a heart-specific extracellular matrix\u2013based hydrogel for the intrapericardial delivery of Astragaloside IV (AS-IV), a pro-angiogenic bioactive monomer derived from traditional Chinese medicine. The bioactive hydrogel is fabricated from decellularized porcine heart extracellular matrix (HdECM), which provides a biomimetic cardiac microenvironment while enabling sustained local release of AS-IV. Distinct from conventional intramyocardial injection, intrapericardial administration allows the hydrogel to form a patch-like depot on the cardiac surface, achieving prolonged cardiac retention with minimal tissue injury. Under oxygen\u2013glucose deprivation, the AS-IV@HdECM hydrogel synergistically enhances endothelial cell survival, migration, and angiogenic capacity while suppressing apoptosis. In a rat MI model, localized delivery of AS-IV via HdECM markedly promotes neovascularization, attenuates myocardial fibrosis, reduces cardiomyocyte apoptosis, and significantly improves cardiac function. Mechanistically, integrative proteomic and network pharmacology analyses, together with experimental validation, indicate that the therapeutic effects are associated with activation of the EGFR\/Raf\u2013MEK\u2013ERK signaling pathway. This work establishes a localized therapeutic paradigm that integrates heart-specific matrix cues with traditional Chinese medicine, offering a translational biomaterials strategy for microvascular regeneration and cardiac repair after MI.<\/jats:p>","DOI":"10.3389\/fbioe.2026.1800990","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:32:54Z","timestamp":1775626374000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A bioactive heart-derived ECM hydrogel potentiates Astragaloside IV\u2013mediated microvascular regeneration"],"prefix":"10.3389","volume":"14","author":[{"given":"Yanxing","family":"Lan","sequence":"first","affiliation":[{"name":"Postgraduate Cultivation Base of Guangzhou University of Chinese Medicine, Panyu Central Hospital","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Xu","sequence":"additional","affiliation":[{"name":"Postgraduate Cultivation Base of Guangzhou University of Chinese Medicine, Panyu Central Hospital","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Li","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital (Dongguan People\u2019s Hospital), Southern Medical University","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahe","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Dongguan Songshan Lake Center Hospital","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenguang","family":"Lu","sequence":"additional","affiliation":[{"name":"Postgraduate Cultivation Base of Guangzhou University of Chinese Medicine, Panyu Central Hospital","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangwei","family":"Li","sequence":"additional","affiliation":[{"name":"South China Normal University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peier","family":"Chen","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital (Dongguan People\u2019s Hospital), Southern Medical University","place":["Dongguan, China"]},{"name":"Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Postgraduate Cultivation Base of Guangzhou University of Chinese Medicine, Panyu Central Hospital","place":["Guangzhou, China"]},{"name":"Cardiovascular Diseases Research Institute of Panyu District","place":["Guangzhou, China"]},{"name":"The Affiliated Panyu Central Hospital, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.pharmthera.2017.08.004","article-title":"Endothelial and cardiac progenitor cells for cardiovascular repair: a controversial paradigm in cell therapy","volume":"181","author":"Bianconi","year":"2018","journal-title":"Pharmacol. and Ther."},{"key":"B2","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1002\/ejhf.1747","article-title":"Ischaemic cardiomyopathy. 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