Abstract
Traditional methods using coupling chemistry for surface grafting of heparin onto polyurethane (PU) are disadvantageous due to their generally low efficiency. In order to overcome this problem, a quick one-step photografting method is proposed here. Three heparin derivatives incorporating 0.21, 0.58, and 0.88 wt% pendant aryl azide groups were immobilized onto PU surfaces, leading to similar grafting densities of 1.07, 1.17, and 1.13 μg/cm2, respectively, yet with increasing densities of anchoring points. The most negatively charged surface and the maximum binding ability towards antithrombin III were found for the heparinized PU with the lowest amount of aryl azide/anchor sites. Furthermore, decreasing the density of anchoring points was found to inhibit platelet adhesion to a larger extent and to prolong plasma recalcification time, prothrombin time, thrombin time, and activated partial thromboplastin time to a larger extent. This was also found to enhance the bioactivity of immobilized heparin from 22.9% for raw heparin to 36.9%. This could be explained by the enhanced molecular mobility of immobilized heparin when it is more loosely anchored to the PU surface, as well as a higher surface charge.
Highlights
Venous catheters are typically placed into a large vein and used to administer medication or fluids, obtain blood tests, and measure central venous pressure [1]
Upon UV irradiation, heparin-bound aryl azides are converted to highly reactive nitrenes which can insert into C–H bonds and yield amines [23]
Our study shows that with this one-step UV irradiation, heparin derivatives can be successfully grafted onto PU surfaces
Summary
Venous catheters are typically placed into a large vein and used to administer medication or fluids, obtain blood tests, and measure central venous pressure [1]. After being placed in vivo for an extended period of time, a catheter faces the risk of blood clots, which is critical for cancer patients as they are inclined to develop these [2]. Anti-clotting drugs such as heparin and fondaparinux decrease the incidence of blood clots. To decrease the potential risks and adverse effects, methods including physical entrapment, as well as ionic and covalent surface binding of heparin or other substances, have been utilized to enhance catheter anticoagulation properties [5]. Compared to physical adsorption or entrapment, covalently heparinizing the surface of catheters provides a robust anticoagulation coating which can withstand long-term exposure in vivo [6]
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