Wu Yong, Chang Tianqi, Chen Weiqian, Wang Xiaoyu, Li Jingjing, Chen Yueqiu, Yu You, Shen Zhenya, Yu Qian, Zhang Yanxia
Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, PR China.
State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, PR China.
Bioact Mater. 2020 Sep 11;6(2):520-528. doi: 10.1016/j.bioactmat.2020.08.031. eCollection 2021 Feb.
Myocardial infarction (MI) is one of cardiovascular diseases that pose a serious threat to human health. The pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery, necrosis of myocardial cells, inflammation, and myocardial fibrosis. Aiming at the treatment of different stages of MI, in this work, an injectable alginate based composite hydrogel is developed to load vascular endothelial active factor (VEGF) and silk fibroin (SF) microspheres containing bone morphogenetic protein 9 (BMP9) for releasing VEGF and BMP9 to realize their respective functions. The results of experiments indicate a rapid initial release of VEGF during the first few days and a relatively slow and sustained release of BMP9 for days, facilitating the formation of blood vessels in the early stage and inhibiting myocardial fibrosis in the long-term stage, respectively. Intramyocardial injection of such composite hydrogel into the infarct border zone of mice MI model via multiple points promotes angiogenesis and reduces the infarction size. Taken together, these results indicate that the dual-release of VEGF and BMP9 from the composite hydrogel results in a collaborative effect on the treatment of MI and improvement of heart function, showing a promising potential for cardiac clinical application.
心肌梗死（MI）是对人类健康构成严重威胁的心血管疾病之一。MI的病理生理学很复杂，包括几个连续阶段，包括冠状动脉阻塞、心肌细胞坏死、炎症和心肌纤维化。针对MI不同阶段的治疗，在本研究中，开发了一种基于注射型藻酸盐的复合水凝胶，用于负载血管内皮活性因子（VEGF）和含有骨形态发生蛋白9（BMP9）的丝素蛋白（SF）微球，以释放VEGF和BMP9来实现它们各自的功能。实验结果表明，VEGF在最初几天快速初始释放，而BMP9则在数天内相对缓慢且持续释放，分别促进早期血管形成和长期抑制心肌纤维化。通过多点将这种复合水凝胶心肌内注射到小鼠MI模型的梗死边缘区，可促进血管生成并减小梗死面积。综上所述，这些结果表明复合水凝胶中VEGF和BMP9的双重释放对MI治疗和心脏功能改善产生协同作用，在心脏临床应用中显示出有前景的潜力。
