Anticoagulant sodium alginate sulfates and their mussel-inspired heparin-mimetic coatings

Abstract

In this work, we synthesized novel sodium alginate sulfates (SASs) with different sulfation degrees, which had similar chemical structure and bioactivity as those of heparin. Blood clotting time tests indicated that the heparin-mimetic SASs exhibited excellent and sulfation-degree-dependent anticoagulant activity. Beyond applications as anticoagulant reagents, the heparin-mimetics also showed potential applications for surface modification of blood-contacting devices. To achieve the goal of surface modification, we synthesized the mussel inspired adhesive macromolecules, dopamine grafted SASs (DA-g-SASs), which were capable of coating the surface of polymeric substrates in a basic buffer solution in a substrate-independent manner. The DA-g-SASs exhibited substrate-independent adhesive affinity to a variety of solid surfaces due to the formation of irreversible covalent bonds. By using polyethersulfone (PES) as a model blood contacting substrate, the surface properties of DA-g-SASs coated substrates were fully explored. ATR-FTIR and XPS spectra demonstrated the successful formation of the heparin-mimetic coatings. Endothelial cell staining and morphological observations revealed that the heparin-mimetic coatings could significantly promote cell adhesion and proliferation. In addition, systematic in vitro studies of blood clotting, protein adsorption, platelet adhesion, and blood-related complement activation demonstrated that the heparin-mimetic macromolecule coated substrates dramatically inhibited the thrombotic potential and inflammation induced by the material interface. Combining the above advantages, it is believed that the proposed integration of heparin-mimetic SASs and mussel inspired coating may open new operational principles for surface anticoagulant modification of various biological and clinical devices for blood purification, tissue implants, and other micro-nanoscale materials.