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生物陶瓷增强贴片通过Notch信号通路激活心外膜上皮-间充质转化以促进心脏修复。

Bioceramics-enhanced patch activates epicardial epithelial-to-mesenchymal transition via Notch pathway for cardiac repair.

作者信息

Ding Chengbin, Qin Chen, Sun Yan, Liu Yueyang, Tang Guofeng, Liao Zhibin, Zhao Chaoran, Wu Chengtie, Wang Leyu

机构信息

Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China.

Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China.

出版信息

Sci Adv. 2025 Jun 6;11(23):eads5978. doi: 10.1126/sciadv.ads5978. Epub 2025 Jun 4.

Abstract

Engineered cardiac patches (ECPs) introduced functional factors that offer a promising strategy for the treatment of myocardial infarction (MI). Silicate bioceramics have received widespread attention because of their great potential in the tissue repair field. Inspired by the biological functions of inorganic ions on the cardiovascular system, we prepared an ECP containing lithium magnesium silicon bioceramics (LMS) particles. The release of multiple bioactive ions from LMS-containing ECPs could facilitate the functionalization and intercellular communication between cardiomyocytes (CMs). Furthermore, it was demonstrated that the LMS-containing ECPs could promote epicardial cell epithelial-to-mesenchymal transition (EMT) through the Notch pathway and paracrine, which efficiently repaired damaged CMs. In vivo, the regenerative microenvironment induced by LMS-containing ECPs restored normal electrical impulse propagation across scar tissue, activated islands of surviving myocardium, and improved cardiac function. Overall, this study constructed a bioceramics-enhanced ECP, which could promote cardiac repair by activating epicardial EMT, providing a promising strategy for MI repair.

摘要

工程化心脏补片(ECPs)引入功能因子,为心肌梗死(MI)的治疗提供了一种有前景的策略。硅酸盐生物陶瓷因其在组织修复领域的巨大潜力而受到广泛关注。受无机离子对心血管系统生物学功能的启发,我们制备了一种含有锂镁硅生物陶瓷(LMS)颗粒的ECP。含LMS的ECP释放多种生物活性离子可促进心肌细胞(CMs)之间的功能化和细胞间通讯。此外,研究表明含LMS的ECP可通过Notch信号通路和旁分泌促进心外膜细胞上皮-间质转化(EMT),从而有效修复受损的CMs。在体内,含LMS的ECP诱导的再生微环境恢复了跨瘢痕组织的正常电冲动传导,激活了存活心肌岛,并改善了心脏功能。总体而言,本研究构建了一种生物陶瓷增强的ECP,其可通过激活心外膜EMT促进心脏修复,为MI修复提供了一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8782/12136047/521f32c1ef70/sciadv.ads5978-f1.jpg

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