Zhang Bo, Wan Huining, Liu Xiyu, Yu Tao, Yang Yuan, Dai Yan, Han Yaling, Xu Kai, Yang Li, Wang Yunbing, Zhang Xingdong
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China.
Sichuan Xingtai Pule Medical Technology Co Ltd, Chengdu, Sichuan 610045, China.
ACS Nano. 2023 Dec 12;17(23):23498-23511. doi: 10.1021/acsnano.3c06103. Epub 2023 Nov 16.
Rapid endothelialization of cardiovascular materials can enhance the vascular remodeling performance. In this work, we developed a strategy for amyloid-like protein-assembly-mediated interfacial engineering to functionalize a biomimetic nanoparticle coating (BMC). Various groups (e.g., hydroxyl and carboxyl) on the BMC are responsible for chelating Zn ions at the stent interface, similar to the glutathione peroxidase-like enzymes found in vivo. This design could reproduce the release of therapeutic nitric oxide gas (NO) and an aligned microenvironment nearly identical with that of natural vessels. In a rabbit abdominal aorta model, BMC-coated stents promoted vascular healing through rapid endothelialization and the inhibition of intimal hyperplasia in the placement sites at 4, 12, and 24 weeks. Additionally, better anticoagulant activity and immunomodulation in the BMC stents were also confirmed, and vascular healing was mainly dependent on cell signaling through the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) cascade. Overall, a metal-polypeptide-coated stent was developed on the basis of its detailed molecular mechanism of action in vascular remodeling.
心血管材料的快速内皮化可增强血管重塑性能。在这项工作中，我们开发了一种策略，用于通过类淀粉样蛋白组装介导的界面工程来功能化仿生纳米颗粒涂层（BMC）。BMC上的各种基团（如羟基和羧基）负责在支架界面螯合锌离子，类似于体内发现的谷胱甘肽过氧化物酶样酶。这种设计可以重现治疗性一氧化氮气体（NO）的释放以及与天然血管几乎相同的排列微环境。在兔腹主动脉模型中，BMC涂层支架在4周、12周和24周时通过快速内皮化和抑制植入部位的内膜增生促进血管愈合。此外，还证实了BMC支架具有更好的抗凝活性和免疫调节作用，并且血管愈合主要依赖于通过环磷酸鸟苷-蛋白激酶G（cGMP-PKG）级联的细胞信号传导。总体而言，基于其在血管重塑中详细的分子作用机制，开发了一种金属-多肽涂层支架。
