Li Minying, Wu Qinghe, Sun Weipeng, Wu Wenhu, Zhao Biyi, Wang Yifei, Wang Wei, Fan Chun, Deng Dong, Meng Fanhang
State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Bioact Mater. 2026 Feb 4;60:590-606. doi: 10.1016/j.bioactmat.2026.01.015. eCollection 2026 Jun.
Myocardial infarction (MI) leads to irreversible cardiomyocyte loss accompanied by oxidative stress, inflammation, and fibrotic remodeling, ultimately progressing to heart failure. Using network pharmacology analysis, salvianolic acid B (DB), a major bioactive component of , was identified as a promising therapeutic candidate for MI. Oral administration of DB showed therapeutic efficacy in functional, molecular, and histological assessments, but its clinical translation is limited by poor bioavailability. To overcome this limitation, we developed an injectable reactive oxygen species (ROS)-responsive hydrogel patch for localized MI repair. The hydrogel, composed of whey protein isolate methacrylate (WPI-MA) and o-nitrobenzyl alcohol modified hyaluronic acid (HA-NB), forms a biocompatible and adhesive network through dynamic covalent interactions. ROS-sensitive liposomes encapsulating DB were incorporated into the hydrogel, enabling localized and on-demand drug release in response to the oxidative microenvironment. studies confirmed that the hydrogel exhibited favorable mechanical strength, selective myocardial adhesiveness, and sustained antioxidant capacity. In a murine MI model, a single administration of the hydrogel patch markedly attenuated fibrosis, promoted angiogenesis, and restored cardiac function. This study establishes a rational design strategy that begins with network pharmacology-based drug discovery, proceeds through validation of therapeutic efficacy, and culminates in the construction of a responsive delivery system, providing a promising approach for localized and sustained post-infarction cardiac repair.
心肌梗死（MI）会导致不可逆的心肌细胞损失，并伴有氧化应激、炎症和纤维化重塑，最终发展为心力衰竭。通过网络药理学分析，丹参酸B（DB），作为[具体药物名称未给出]的主要生物活性成分，被确定为MI的一种有前景的治疗候选药物。口服DB在功能、分子和组织学评估中显示出治疗效果，但其临床转化受到生物利用度差的限制。为了克服这一限制，我们开发了一种用于局部心肌梗死修复的可注射活性氧（ROS）响应水凝胶贴片。该水凝胶由甲基丙烯酸乳清蛋白分离物（WPI-MA）和邻硝基苄醇修饰的透明质酸（HA-NB）组成，通过动态共价相互作用形成生物相容性和粘附性网络。包裹DB的ROS敏感脂质体被掺入水凝胶中，能够响应氧化微环境进行局部和按需药物释放。研究证实，该水凝胶具有良好的机械强度、选择性心肌粘附性和持续抗氧化能力。在小鼠心肌梗死模型中，单次施用该水凝胶贴片可显著减轻纤维化、促进血管生成并恢复心脏功能。本研究建立了一种合理的设计策略，从基于网络药理学的药物发现开始，经过治疗效果验证，最终构建响应性递送系统，为局部和持续的心肌梗死后心脏修复提供了一种有前景的方法。
