Wu Yu, Zhang Wen, Huang Linlin, Xu Xinping, He Shuyi, Wang Zhicun, Liu Wenqi, Yao Ya, Yang Li, Hu Cheng, Wang Yunbing
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Med-X Center for Materials, Sichuan University, Chengdu, 610064, People's Republic of China.
Research Unit of Minimally Invasive Treatment of Structural Heart Disease, Chinese Academy of Medical Sciences (No: 2021RU013), China.
Adv Healthc Mater. 2025 Apr;14(11):e2500804. doi: 10.1002/adhm.202500804. Epub 2025 Mar 4.
Despite the development of many injectable hydrogels intended for the repair of myocardial infarction (MI), their effectiveness is often compromised because they target merely one or two phases of MI's pathological progression. Here, a multifunctional hydrogel delivery platform is prepared with a brand-new small molecule cross-linker for stepwise treatment of MI. The synthesis and reporting of a novel small-molecule phenylboronic acid cross-linker ((N(BA))) with a precise molecular structure is conducted for the first time, and it is successfully utilized with polyvinyl alcohol (PVA) dopamine to prepare a hydrogel with infarct microenvironmental responsiveness and anti-oxidant. Further, considering the multistage of MI repair, hydrogel contains both hyperoside bioactive nanoparticles (EGCG@Hyp&Arg NPs) and PLGA microspheres loaded with galunisertib (PLGA@Gal Ms). The EGCG@Hyp&Arg NPs are rapidly released and demonstrate anti-inflammatory and pro-angiogenesis effects, while in the long term, Gal is released from the PLGA@Gal Ms to inhibit myocardial fibrosis and improve cardiac function. Results from both in vitro and in vivo studies reveal that the hydrogel is engineered with programmed capabilities for anti-oxidation, reducing inflammation, promoting new blood vessel formation, and inhibiting fibrosis, thereby significantly enhancing heart function post-MI. Overall, this multifunctional hydrogel delivery platform has great potential for application as a therapeutic strategy for MI.
尽管已经开发出许多用于修复心肌梗死（MI）的可注射水凝胶，但其有效性常常受到影响，因为它们仅针对MI病理进展的一两个阶段。在此，我们制备了一种多功能水凝胶递送平台，其采用全新的小分子交联剂用于MI的分步治疗。首次进行了具有精确分子结构的新型小分子苯基硼酸交联剂（(N(BA))）的合成与报道，并成功将其与聚乙烯醇（PVA）多巴胺一起用于制备具有梗死微环境响应性和抗氧化性的水凝胶。此外，考虑到MI修复的多阶段特性，水凝胶同时包含金丝桃苷生物活性纳米颗粒（EGCG@Hyp&Arg NPs）和负载有galunisertib的聚乳酸-羟基乙酸共聚物微球（PLGA@Gal Ms）。EGCG@Hyp&Arg NPs迅速释放并表现出抗炎和促血管生成作用，而从长期来看，Gal从PLGA@Gal Ms中释放以抑制心肌纤维化并改善心脏功能。体外和体内研究结果均表明，该水凝胶具有抗氧化、减轻炎症、促进新血管形成和抑制纤维化的程序化能力，从而显著增强MI后的心脏功能。总体而言，这种多功能水凝胶递送平台作为MI的治疗策略具有巨大的应用潜力。
