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Improved Polymer Hemocompatibility for Blood-Contacting Applications via S-Nitrosoglutathione Impregnation
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-02-28 , DOI: 10.1021/acsami.1c24557
Lauren Griffin 1 , Megan Douglass 1 , Marcus Goudie 1 , Sean P Hopkins 1 , Chad Schmiedt 2 , Hitesh Handa 1, 3
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-02-28 , DOI: 10.1021/acsami.1c24557
Lauren Griffin 1 , Megan Douglass 1 , Marcus Goudie 1 , Sean P Hopkins 1 , Chad Schmiedt 2 , Hitesh Handa 1, 3
Affiliation
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Blood-contacting medical devices (BCMDs) are inevitably challenged by thrombi formation, leading to occlusion of flow and device failure. Ideal BCMDs seek to mimic the intrinsic antithrombotic properties of the human vasculature to locally prevent thrombotic complications, negating the need for systemic anticoagulation. An emerging category of BCMD technology utilizes nitric oxide (NO) as a hemocompatible agent, as the vasculature’s endothelial layer naturally releases NO to inhibit platelet activation and consumption. In this paper, we report for the first time the novel impregnation of S-nitrosoglutathione (GSNO) into polymeric poly(vinyl chloride) (PVC) tubing via an optimized solvent-swelling method. Material testing revealed an optimized GSNO–PVC material that had adequate GSNO loading to achieve NO flux values within the physiological endothelial NO flux range for a 4 h period. Through in vitro hemocompatibility testing, the optimized material was deemed nonhemolytic (hemolytic index <2%) and capable of reducing platelet activation, suggesting that the material is suitable for contact with whole blood. Furthermore, an in vivo 4 h extracorporeal circulation (ECC) rabbit thrombogenicity model confirmed the blood biocompatibility of the optimized GSNO–PVC. Platelet count remained near 100% for the novel GSNO-impregnated PVC loops (1 h, 91.08 ± 6.27%; 2 h, 95.68 ± 0.61%; 3 h, 97.56 ± 8.59%; 4 h, 95.11 ± 8.30%). In contrast, unmodified PVC ECC loops occluded shortly after the 2 h time point and viable platelet counts quickly diminished (1 h, 85.67 ± 12.62%; 2 h, 54.46 ± 10.53%; 3 h, n/a; 4 h, n/a). The blood clots for GSNO–PVC loops (190.73 ± 72.46 mg) compared to those of unmodified PVC loops (866.50 ± 197.98 mg) were significantly smaller (p < 0.01). The results presented in this paper recommend further investigation in long-term animal models and suggest that GSNO–PVC has the potential to serve as an alternative to systemic anticoagulation in BCMD applications.
中文翻译:
通过 S-亚硝基谷胱甘肽浸渍改善血液接触应用的聚合物血液相容性
血液接触医疗设备 (BCMD) 不可避免地会受到血栓形成的挑战,从而导致血流阻塞和设备故障。理想的 BCMD 寻求模仿人体血管系统的内在抗血栓形成特性,以局部预防血栓形成并发症,从而无需全身抗凝。一类新兴的 BCMD 技术利用一氧化氮 (NO) 作为血液相容剂,因为脉管系统的内皮层自然释放 NO 以抑制血小板活化和消耗。在本文中,我们首次报道了S的新型浸渍-亚硝基谷胱甘肽 (GSNO) 通过优化的溶剂溶胀方法进入聚合聚氯乙烯 (PVC) 管中。材料测试揭示了一种优化的 GSNO-PVC 材料,该材料具有足够的 GSNO 负载量,可在 4 小时内实现生理内皮 NO 通量范围内的 NO 通量值。通过体外血液相容性测试,优化后的材料被认为是非溶血性的(溶血指数<2%)并且能够降低血小板活化,表明该材料适合与全血接触。此外,体内4 小时体外循环 (ECC) 兔血栓形成模型证实了优化后的 GSNO-PVC 的血液生物相容性。新型 GSNO 浸渍 PVC 环的血小板计数保持在接近 100%(1 小时,91.08 ± 6.27%;2 小时,95.68 ± 0.61%;3 小时,97.56 ± 8.59%;4 小时,95.11 ± 8.30%)。相比之下,未修改的 PVC ECC 循环在 2 小时时间点后不久发生阻塞,活血小板计数迅速减少(1 小时,85.67 ± 12.62%;2 小时,54.46 ± 10.53%;3 小时,n/a;4 小时,n/ A)。与未改性 PVC 环 (866.50 ± 197.98 mg) 相比,GSNO–PVC 环 (190.73 ± 72.46 mg) 的血块明显更小 ( p< 0.01)。本文中的结果建议对长期动物模型进行进一步研究,并表明 GSNO-PVC 有可能在 BCMD 应用中作为全身抗凝的替代品。
更新日期:2022-02-28
中文翻译:
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通过 S-亚硝基谷胱甘肽浸渍改善血液接触应用的聚合物血液相容性
血液接触医疗设备 (BCMD) 不可避免地会受到血栓形成的挑战,从而导致血流阻塞和设备故障。理想的 BCMD 寻求模仿人体血管系统的内在抗血栓形成特性,以局部预防血栓形成并发症,从而无需全身抗凝。一类新兴的 BCMD 技术利用一氧化氮 (NO) 作为血液相容剂,因为脉管系统的内皮层自然释放 NO 以抑制血小板活化和消耗。在本文中,我们首次报道了S的新型浸渍-亚硝基谷胱甘肽 (GSNO) 通过优化的溶剂溶胀方法进入聚合聚氯乙烯 (PVC) 管中。材料测试揭示了一种优化的 GSNO-PVC 材料,该材料具有足够的 GSNO 负载量,可在 4 小时内实现生理内皮 NO 通量范围内的 NO 通量值。通过体外血液相容性测试,优化后的材料被认为是非溶血性的(溶血指数<2%)并且能够降低血小板活化,表明该材料适合与全血接触。此外,体内4 小时体外循环 (ECC) 兔血栓形成模型证实了优化后的 GSNO-PVC 的血液生物相容性。新型 GSNO 浸渍 PVC 环的血小板计数保持在接近 100%(1 小时,91.08 ± 6.27%;2 小时,95.68 ± 0.61%;3 小时,97.56 ± 8.59%;4 小时,95.11 ± 8.30%)。相比之下,未修改的 PVC ECC 循环在 2 小时时间点后不久发生阻塞,活血小板计数迅速减少(1 小时,85.67 ± 12.62%;2 小时,54.46 ± 10.53%;3 小时,n/a;4 小时,n/ A)。与未改性 PVC 环 (866.50 ± 197.98 mg) 相比,GSNO–PVC 环 (190.73 ± 72.46 mg) 的血块明显更小 ( p< 0.01)。本文中的结果建议对长期动物模型进行进一步研究,并表明 GSNO-PVC 有可能在 BCMD 应用中作为全身抗凝的替代品。