Roberts Teryn R, Garren Mark R S, Wilson Sarah N, Handa Hitesh, Batchinsky Andriy I
Autonomous Reanimation and Evacuation Research Program, The Geneva Foundation, 2509 Kennedy Circle Bldg 125, San Antonio, Texas 78235, United States.
School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens, Georgia 30602, United States.
ACS Appl Bio Mater. 2022 May 16;5(5):2212-2223. doi: 10.1021/acsabm.2c00073. Epub 2022 Apr 11.
Multifunctional antithrombotic surface modifications for blood-contacting medical devices have emerged as a solution for foreign surface-mediated coagulation disturbance. Herein, we have developed and evaluated an endothelium-inspired strategy to reduce the thrombogenicity of medical plastics by imparting nitric oxide (NO) elution and heparin immobilization on the material surface. This dual-action approach (NO+Hep) was applied to polyethylene terephthalate (PET) blood incubation vials and compared to isolated modifications. Vials were characterized to evaluate NO surface flux as well as heparin density and activity. Hemocompatibility was assessed using whole blood from human donors. Compared to unmodified surfaces, blood incubated in the NO+Hep vials exhibited reduced platelet aggregation (15% decrease AUC, = 0.040) and prolonged plasma clotting times (aPTT = 147% increase, < 0.0001, prothrombin time = 5% increase, = 0.0002). Prolongation of thromboelastography reaction time and elevated antifactor Xa levels in blood from NO+Hep versus PET vials suggests some heparin leaching from the vial surface, confirmed by post-blood incubation heparin density assessment. Results suggest NO+Hep surface modification is a promising approach for blood-contacting plastics; however, careful tuning of NO flux and heparin stabilization are essential and require assessment using human blood as performed here.
用于血液接触医疗设备的多功能抗血栓表面改性技术已成为解决外来表面介导的凝血紊乱问题的一种方法。在此,我们开发并评估了一种受内皮启发的策略,通过在材料表面实现一氧化氮(NO)洗脱和肝素固定来降低医用塑料的血栓形成性。这种双作用方法(NO + 肝素)应用于聚对苯二甲酸乙二酯(PET)血液培养瓶,并与单独的改性方法进行比较。对培养瓶进行表征以评估NO表面通量以及肝素密度和活性。使用人类供体的全血评估血液相容性。与未改性表面相比,在NO + 肝素培养瓶中孵育的血液表现出血小板聚集减少(曲线下面积减少15%,P = 0.040)和血浆凝血时间延长(活化部分凝血活酶时间增加147%,P < 0.0001,凝血酶原时间增加5%,P = 0.0002)。与PET培养瓶相比,NO + 肝素培养瓶中血液的血栓弹力图反应时间延长和抗Xa因子水平升高表明有一些肝素从培养瓶表面浸出,血液孵育后肝素密度评估证实了这一点。结果表明,NO + 肝素表面改性是用于血液接触塑料的一种有前景的方法;然而,仔细调节NO通量和肝素稳定性至关重要,并且需要像在此处一样使用人类血液进行评估。