Multistage Anticoagulant Surfaces: A Synergistic Combination of Protein Resistance, Fibrinolysis, and Endothelialization

Anticoagulantsurface modification of blood-contacting materialshas been shown to be effective in preventing thrombosis and reducingthe dose of anticoagulant drugs that patients take. However, commerciallyavailable anticoagulant coatings, that is, both bioinert and bioactivecoatings, are typically based on a single anticoagulation strategy.This puts the anticoagulation function of the coating at risk of failureduring long-term use. Considering the several pathways of the humancoagulation system, the synergy of multiple anticoagulation theoriesmay provide separate, targeted effects at different stages of thrombosis.Based on this presumption, in this work, negatively charged poly(sodium p-styrenesulfonate-co-oligo(ethylene glycol)methyl ether methacrylate) and positively charged poly(lysine-co-1-adamantan-1-ylmethyl methacrylate) were synthesizedto construct matrix layers on the substrate by electrostatic layer-by-layerself-assembly (LBL). Amino-functionalized & beta;-cyclodextrin (& beta;-CD-PEI)was subsequently immobilized on the surface by host-guest interactions,and heparin was grafted. By adjusting the content of poly(oligo(ethyleneglycol) methyl ether methacrylate) (POEGMA), the interactions betweenmodified surfaces and plasma proteins/cells were regulated. This multistageanticoagulant surface exhibits inertness at the initial stage of implantation,resisting nonspecific protein adsorption (POEGMA). When coagulationreactions occur, heparin exerts its active anticoagulant functionin a timely manner, blocking the pathway of thrombosis. If thrombusformation is inevitable, lysine can play a fibrinolytic role in dissolvingfibrin clots. Finally, during implantation, endothelial cells continueto adhere and proliferate on the surface, forming an endothelial layer,which meets the blood compatibility requirements. This method providesa new approach to construct a multistage anticoagulant surface forblood-contacting materials.