2, Laval University, Quebec, Quebec, Canada
Thrombosis constitute the main clinical problem when blood-interacting devices are implanted in the body. Coatings with thin polymer layers represent a recognized strategy to modulate interactions between the material surface and the blood environment. To provide the implant success, the coating should limit platelets adhesion and delay the clot formation. Scientists have focused in many strategies, using chemical and physical modifications, to improving polymers hemocompatibility. One possibility is the introduction of sulfate or sulfonate groups in chitosan chain. This natural polymer has attracted attention due to its potential to act as a biomaterial, to mimic the effects promoted by heparin, one of the most used anticoagulant. Sulfur-containing chitosan, shows the ability to reduce proteins adsorption, decrease thrombogenic properties and limit clot formation. In this context, we produced two types of chitosan membranes: one with chlorossulfonic acid, to form 2,N-3,6,O-sulfated chitosan, and other with 5-Formyl-2-furansulfonic acid sodium salt (FFSA), to obtain N-sulfonated chitosan. The membranes were characterized and its effects over proteins adsorption and platelet adhesion evaluated. 1H-13C NMR and FT-IR analysis confirmed the N and O substitution of chitosan when treated with chlorossulfonic acid, while FTIR and XPS analysis evidenced the sulfonation by FFSA. The 2,N-3,6,O-sulfated chitosan showed decrease in the bovine serum albumin-BSA (36.8%) and fibrinogen (20%) adsorption, and in the platelet adhesion (93.7%), which was observed by SEM images. For N-sulfonated chitosan, a more pronounced adsorption rate was observed at pH 5.0 than at pH 7.4, and the adsorption equilibrium was achieved, in both cases, after approximately 20 min. The platelet adhesion was about 50% lower than that of native chitosan. Afterwards, stainless steel surfaces, commonly used for cardiovascular applications, were coated with sulfonated chitosan, by using dopamine and PEG as anchors, and the effect of these grafted surfaces on platelet adhesion and clot formation were investigated. Surface characterization techniques evidenced that the coating formation was successful, and the sulfonated chitosan grafted sample exhibited a higher roughness and hydrophilicity, if compared to native chitosan one. Moreover, sulfonated surface limited platelet activation and the process of clot formation, thus confirming its high biological performances in blood. In conclusion, this sulfonated-modified chitosan has potential to be used as blood-interacting material.