Department of Cardiology, the Second Affiliated Hospital of Kunming Medical University, Kunming 650101, P. R. China.
Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, P. R. China.
J Mater Chem B. 2022 Aug 31;10(34):6514-6531. doi: 10.1039/d2tb00623e.
Myocardial infarction (MI) is a common cardiovascular disease that seriously endangers human health and complex pathophysiology (, coronary artery obstruction, myocardial apoptosis, necrosis, inflammation, fibrosis, ) is involved. Therein, the loss of cardiomyocytes after MI in adults leads to gradual heart failure, which probably brings irreparable damage to the patient. Unfortunately, due to a cluster of limitations, currently used MI repair approaches always exhibit simple functions, low efficiency, and can hardly match the myocardial ischemia environment and clinical needs. In this study, we selected oncostatin M (OSM), a pleiotropic cytokine belonging to the interleukin-6 family that possesses an important role in cardiomyocyte dedifferentiation, cell proliferation, and regulation of inflammatory processes. Moreover, an injectable hydrogel with pH- and temperature-responsive behavior that can react with the acidic microenvironment of the ischemic myocardium was developed to deliver OSM locally. The functional hydrogel (poly (chitosan--citric acid--isopropyl acrylamide), P(CS-CA-NIPAM)) was fabricated by the facile reversible addition-fragmentation chain transfer polymerization and can be injected into the lesion site directly. After the gelation , the OSM-loaded hydrogel exhibited continuous and localized release of OSM in response to specific pH and changes in MI rats, thereby accelerating angiogenesis and proliferation of cardiomyocytes, inhibiting myocardial fibrosis and improving cardiac function effectively. This study may provide a new perspective for the application of dual-sensitive hydrogels clinically, especially in tissue engineering for MI repair and drug delivery.
心肌梗死（MI）是一种常见的心血管疾病，严重危害人类健康，其复杂的病理生理学（，冠状动脉阻塞，心肌细胞凋亡、坏死、炎症、纤维化，）涉及其中。在成年人中，MI 后心肌细胞的丧失导致逐渐出现心力衰竭，这可能会给患者带来不可挽回的损害。不幸的是，由于一系列的局限性，目前用于 MI 修复的方法通常表现出简单的功能、低效率，并且很难与心肌缺血环境和临床需求相匹配。在这项研究中，我们选择了集落刺激因子 M（OSM），一种属于白细胞介素-6 家族的多功能细胞因子，在心肌细胞去分化、细胞增殖和炎症过程调节中具有重要作用。此外，我们开发了一种具有 pH 和温度响应行为的可注射水凝胶，可与缺血性心肌的酸性微环境发生反应，从而实现 OSM 的局部递送。功能水凝胶（聚（壳聚糖-柠檬酸-异丙基丙烯酰胺），P（CS-CA-NIPAM））是通过简单的可逆加成-断裂链转移聚合制备的，可直接注入病变部位。凝胶化后，载有 OSM 的水凝胶可响应特定的 pH 值和 MI 大鼠的变化，持续且局部地释放 OSM，从而有效促进血管生成和心肌细胞增殖，抑制心肌纤维化并改善心脏功能。这项研究可能为双敏感水凝胶的临床应用提供新的视角，特别是在 MI 修复和药物输送的组织工程中。
