Exploiting endogenous nitric oxide to improve the haemocompatibility of biomaterials

Scope of study. Blood-contacting polymeric biomaterials have been widely utilized as components of blood oxygenators, kidney dialyzers, and other vascular grafts to improve human life. Polyurethane (PU) and polyethylene terephthalate (PET) are two important biomedical materials because of their relatively good haemocompatibility (blood compatibility) as well as their superior mechanical properties. However, applications of these materials are still complicated by some platelet adhesion, aggregation, and emboli formation. To improve the haemocompatibility of these polymers, a novel method was developed to exploit the platelet inhibition attributes of endogenous nitric oxide, a small biological molecule.; Findings and conclusions. The surfaces of PU and PET were successfully modified with L-cysteine to extract NO via transnitrosation from endogenous nitroso-proteins in blood plasma, followed by NO release from the polymer surface to inhibit platelet adhesion. This mechanism is supported by the experimental evidence. The kinetic rate constants for transnitrosation between S-nitrosated bovine serum albumin and L-cysteine-modified PET were measured and will be beneficial for characterizing the NO release rate when L-cysteine-modification is used for inhibiting platelet adhesion via NO release. The haemocompatibility of the modified polymers was evaluated in terms of the number of adhered platelets when exposed to a platelet suspension labeled with Cr51. Both stagnant and flow tests showed that platelet adherence to the L-cysteine modified polymers was reduced more than 50% as compared to the control when the platelet suspension contained plasma constituents. The benefits of the modified polymers include potential long-term inhibition of platelet adhesion, non-toxicity, and constant NO release rate. Additionally, a chemiluminescence-based assay of free and immobilized L-cysteine was presented to quantify the L-cysteine attached on PU and PET.