State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P.R. China.
The SIP Biointerface Engineering Research Institute, Suzhou 215123, P.R. China.
ACS Appl Mater Interfaces. 2023 Aug 2;15(30):35860-35871. doi: 10.1021/acsami.3c05145. Epub 2023 Jul 19.
Anticoagulant surface modification of blood-contacting materials has been shown to be effective in preventing thrombosis and reducing the dose of anticoagulant drugs that patients take. However, commercially available anticoagulant coatings, that is, both bioinert and bioactive coatings, are typically based on a single anticoagulation strategy. This puts the anticoagulation function of the coating at risk of failure during long-term use. Considering the several pathways of the human coagulation system, the synergy of multiple anticoagulation theories may provide separate, targeted effects at different stages of thrombosis. Based on this presumption, in this work, negatively charged poly(sodium -styrenesulfonate--oligo(ethylene glycol) methyl ether methacrylate) and positively charged poly(lysine--1-adamantan-1-ylmethyl methacrylate) were synthesized to construct matrix layers on the substrate by electrostatic layer-by-layer self-assembly (LBL). Amino-functionalized β-cyclodextrin (β-CD-PEI) was subsequently immobilized on the surface by host-guest interactions, and heparin was grafted. By adjusting the content of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), the interactions between modified surfaces and plasma proteins/cells were regulated. This multistage anticoagulant surface exhibits inertness at the initial stage of implantation, resisting nonspecific protein adsorption (POEGMA). When coagulation reactions occur, heparin exerts its active anticoagulant function in a timely manner, blocking the pathway of thrombosis. If thrombus formation is inevitable, lysine can play a fibrinolytic role in dissolving fibrin clots. Finally, during implantation, endothelial cells continue to adhere and proliferate on the surface, forming an endothelial layer, which meets the blood compatibility requirements. This method provides a new approach to construct a multistage anticoagulant surface for blood-contacting materials.
抗凝血表面改性已被证明可有效预防血栓形成，并减少患者服用的抗凝药物剂量。然而，市售的抗凝涂层，即生物惰性和生物活性涂层，通常基于单一抗凝策略。这使得涂层的抗凝功能在长期使用过程中存在失效的风险。考虑到人体凝血系统的多个途径，多种抗凝理论的协同作用可能在血栓形成的不同阶段提供独立的靶向作用。基于这一假设，在这项工作中，我们合成了带负电荷的聚（苯乙烯磺酸钠-聚乙二醇甲基醚甲基丙烯酸酯）和带正电荷的聚（赖氨酸-1-金刚烷-1-基甲基甲基丙烯酸酯），通过静电层层自组装（LBL）在基底上构建基质层。随后通过主客体相互作用将氨基功能化的β-环糊精（β-CD-PEI）固定在表面上，并接枝肝素。通过调整聚（聚乙二醇甲基醚甲基丙烯酸酯）（POEGMA）的含量，调节改性表面与血浆蛋白/细胞的相互作用。这种多阶段抗凝表面在植入的初始阶段表现出惰性，抵抗非特异性蛋白吸附（POEGMA）。当发生凝血反应时，肝素及时发挥其主动抗凝功能，阻断血栓形成途径。如果血栓形成不可避免，赖氨酸可以在溶解纤维蛋白凝块方面发挥纤溶作用。最后，在植入过程中，内皮细胞继续在表面黏附和增殖，形成内皮层，满足血液相容性要求。该方法为构建用于与血液接触的材料的多阶段抗凝表面提供了一种新方法。
