Roberts Teryn R, Harea George T, Zang Yanyi, Devine Ryan P, Maffe Patrick, Handa Hitesh, Batchinsky Andriy I
Autonomous Reanimation and Evacuation Research Program, The Geneva Foundation, San Antonio, Texas, USA.
School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens, Georgia, USA.
J Biomed Mater Res B Appl Biomater. 2023 Apr;111(4):923-932. doi: 10.1002/jbm.b.35202. Epub 2022 Nov 20.
Numerous biomaterials have been developed for application in blood-contacting medical devices to prevent thrombosis; however, few materials have been applied to full-scale devices and evaluated for hemocompatibility under clinical blood flow conditions. We applied a dual-action slippery liquid-infused (LI) nitric oxide (NO)-releasing material modification (LINO) to full-scale blood circulation tubing for extracorporeal lung support and evaluated the tubing ex vivo using swine whole blood circulated for 6 h at a clinically relevant flow. LINO tubing was compared to unmodified tubing (CTRL) and isolated LI and NO-releasing modifications (n = 9/group). The primary objective was to evaluate safety and blood compatibility of this approach, prior to progression to in vivo testing of efficacy in animal models. The secondary objective was to evaluate coagulation outcomes relevant to hemocompatibility. No untoward effects of the coating, such as elevated methemoglobin fraction, were observed. Additionally, LINO delayed platelet loss until 6 h versus the reduction in platelet count in CTRL at 3 h. At 6 h, LINO significantly reduced the concentration of platelets in an activated P-selectin expressing state versus CTRL (32 ± 1% decrease, p = .02). Blood clot deposition was significantly reduced on LINO blood pumps (p = .007) and numerically reduced on tubing versus CTRL. Following blood exposure, LINO tubing continued to produce a measurable NO-flux (0.20 ± 0.06 × 10 mol cm min ). LINO is a potential solution to reduce circuit-related bleeding and clotting during extracorporeal organ support, pending future extended testing in vivo using full-scale extracorporeal lung support devices.
为了防止血栓形成，人们已经开发了许多生物材料用于与血液接触的医疗设备；然而，很少有材料被应用于全尺寸设备并在临床血流条件下评估其血液相容性。我们将双作用滑液注入（LI）一氧化氮（NO）释放材料改性（LINO）应用于用于体外肺支持的全尺寸血液循环管道，并使用猪全血在临床相关流量下循环6小时对该管道进行体外评估。将LINO管道与未改性的管道（CTRL）以及单独的LI和NO释放改性进行比较（每组n = 9）。主要目标是在推进动物模型体内疗效测试之前，评估这种方法的安全性和血液相容性。次要目标是评估与血液相容性相关的凝血结果。未观察到涂层有任何不良影响，如高铁血红蛋白分数升高。此外，与CTRL在3小时时血小板计数降低相比，LINO将血小板损失延迟至6小时。在6小时时，与CTRL相比，LINO显著降低了处于活化P-选择素表达状态的血小板浓度（降低32±1%，p = 0.02）。LINO血泵上的血凝块沉积显著减少（p = 0.007），管道上的血凝块沉积与CTRL相比在数值上有所减少。血液暴露后，LINO管道继续产生可测量的NO通量（0.20±0.06×10 摩尔·厘米·分钟 ）。在使用全尺寸体外肺支持设备进行未来体内扩展测试之前，LINO是减少体外器官支持期间与回路相关的出血和凝血的潜在解决方案。
