Antithrombotic coating with sheltered positive charges prevents contact activation by controlling factor XII–biointerface binding

作者：Haifeng Ji, Kai Yu, Srinivas Abbina, Lin Xu, Tao Xu, Shengjun Cheng, Sreeparna Vappala, S. M. Amin Arefi, Md Mohosin Rana, Irina Chafeeva, Matthew Drayton, Kevin C. Gonzalez, Yun Liu, Dana Grecov, Edward M. Conway, Weifeng Zhao, Changsheng Zhao, Jayachandran N. Kizhakkedathu · 发表于：Nature Materials · 年份：2024 · DOI：10.1038/s41563-024-02046-0 · 被引用次数：50 · 研究领域：Coagulation, Bradykinin, Polyphosphates, and Angioedema、Polymer Surface Interaction Studies、biodegradable polymer synthesis and properties

Antithrombotic surfaces that prevent coagulation activation without interfering with haemostasis are required for blood-contacting devices. Such materials would restrain device-induced thrombogenesis and decrease the need for anticoagulant use, thereby reducing unwanted bleeding. Here, by optimizing the interactions with coagulation factor XII rather than preventing its surface adsorption, we develop a substrate-independent antithrombotic polymeric coating with sheltered positive charges. The antithrombic properties of the coating were demonstrated in vitro with human blood and in vivo using a carotid artery-jugular vein shunt model in rabbits. The coating exhibits a strong interaction with factor XII, but results in a low reciprocal activation of the contact pathway that triggers clot formation. These findings contradict the prevailing strategy of designing antithrombotic materials through protein-repelling surfaces. Overall, the polymeric coating we describe can benefit most blood-contacting devices and is a useful engineering guideline for designing surfaces with improved antithrombotic properties.