Injection of ROS-Responsive Hydrogel Loaded with Basic Fibroblast Growth Factor into the Pericardial Cavity for Heart Repair
Injection of ROS-Responsive Hydrogel Loaded with Basic Fibroblast Growth Factor into the Pericardial Cavity for Heart Repair
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DOI：
10.1002/adfm.202004377
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发表时间：
2021-02-04
影响因子：
19
通讯作者：
Wang, Xiaojie
中科院分区：
文献类型：
--
作者：
Li, Zhenhua;Zhu, Dashuai;Wang, Xiaojie
在其他缺血性心脏病中，心肌梗死是心脏病患者死亡和发病的主要原因。及时的缺血心肌再通是治疗心肌梗死最有效的方法。然而，缺血组织的血液再灌流会导致有毒活性氧自由基(ROS)的过量产生，从而在缺血损伤的基础上进一步加剧心肌损伤。ROS已被用作缺血再灌注(I/R)损伤的诊断标记物和治疗靶点，并被用作触发药物释放的环境刺激。在本研究中，合成了一种ROS敏感的交联型聚乙烯醇(PVA)水凝胶，用于输送碱性成纤维细胞生长因子(BFGF)用于心肌修复。治疗凝胶被注射到心包腔内。在交付时，水凝胶在心脏表面铺展，并在原位形成心外膜补片。在大鼠心肌I/R损伤模型中，凝胶中释放出的碱性成纤维细胞生长因子可穿透心肌。这种干预措施保护了心脏功能，减少了I/R后心脏的纤维化，增强了血管肌肉的生成。此外，在猪和人类患者中，微创注射和进入心包腔的安全性和可行性都得到了证明。
Myocardial infarction, among other ischemic heart diseases, is the major cause of mortality and morbidity for patients who have heart diseases. Timely reperfusion of the ischemic myocardium is the most effective way to treat myocardial infarction. However, blood reperfusion to the ischemic tissues leads to an overproduction of toxic reactive oxygen species (ROS), which can further exacerbate myocardial damage on top of ischemic injury. ROS has been used as a diagnostic marker and therapeutic target for ischemia-reperfusion (I/R) injury and as an environmental stimulus to trigger drug release. In this study, a ROS-sensitive cross-linked poly(vinyl alcohol) (PVA) hydrogel is synthesized to deliver basic fibroblast growth factor (bFGF) for myocardial repair. The therapeutic gel is injected into the pericardial cavity. Upon delivery, the hydrogel spread on the surface of the heart and form an epicardiac patch in situ. In a rat model of I/R injury, bFGF released from the gel could penetrate the myocardium. Such intervention protects cardiac function and reduces fibrosis in the post-I/R heart, with enhanced angiomyogenesis. Furthermore, the safety and feasibility of minimally invasive injection and access into the pericardial cavity in both pigs and human patients are demonstrated.