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Antithrombotic coating with sheltered positive charges prevents contact activation by controlling factor XII–biointerface binding
Nature Materials ( IF 37.2 ) Pub Date : 2024-11-12 , DOI: 10.1038/s41563-024-02046-0
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 Gonzalez, Yun Liu, Dana Grecov, Edward M. Conway, Weifeng Zhao, Changsheng Zhao, Jayachandran N. Kizhakkedathu

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.



中文翻译:


带有遮蔽性正电荷的抗血栓涂层通过控制因子 XII-生物界面结合来防止接触激活



血液接触装置需要防止凝血激活而不干扰止血的抗血栓形成表面。这种材料将抑制设备诱导的血栓形成并减少对抗凝剂使用的需求,从而减少不必要的出血。在这里,通过优化与凝血因子 XII 的相互作用而不是阻止其表面吸附,我们开发了一种具有屏蔽正电荷的不依赖基材的抗血栓聚合物涂层。涂层的抗血栓特性在体外用人血液和体内使用兔颈动脉-颈静脉分流模型得到证明。该涂层与因子 XII 表现出很强的相互作用,但导致触发凝块形成的接触途径的低相互激活。这些发现与通过蛋白质排斥表面设计抗血栓形成材料的流行策略相矛盾。总体而言,我们描述的聚合物涂层可以使大多数血液接触设备受益,并且是设计具有改进抗血栓形成特性的表面的有用工程指南。

更新日期:2024-11-12
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