Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Artif Organs. 2022 Dec;46(12):2400-2411. doi: 10.1111/aor.14366. Epub 2022 Jul 30.
To determine suitable alternatives to human blood for in vitro dynamic thrombogenicity testing of biomaterials, four different animal blood sources (ovine, bovine, and porcine blood from live donors, and abattoir porcine blood) were compared to fresh human blood.
To account for blood coagulability differences between individual donors and species, each blood pool was heparinized to a donor-specific concentration immediately before testing in a dynamic flow loop system. The target heparin level was established using a static thrombosis pre-test. For dynamic testing, whole blood was recirculated at room temperature for 1 h at 200 ml/min through a flow loop containing a single test material. Four materials with varying thrombotic potentials were investigated: latex (positive control), polytetrafluoroethylene (PTFE) (negative control), silicone (intermediate thrombotic potential), and high-density polyethylene (HDPE) (historically thromboresistant). Thrombus weight and surface area coverage on the test materials were quantified, along with platelet count reduction in the blood.
While donor-specific heparin levels varied substantially from 0.6 U/ml to 7.0 U/ml among the different blood sources, each source was able to differentiate between the thrombogenic latex and the thromboresistant PTFE and HDPE materials (p < 0.05). However, only donor ovine and bovine blood were sensitive enough to differentiate an increased response for the intermediate thrombotic silicone material compared to PTFE and HDPE.
These results demonstrated that multiple animal blood sources (particularly donor ovine and bovine blood) may be suitable alternatives to fresh human blood for dynamic thrombogenicity testing when appropriate control materials and donor-specific anticoagulation levels are used.
为了确定替代人血用于生物材料体外动态血栓形成性测试的合适替代品，将四种不同的动物血液来源（来自活体供体的绵羊、牛和猪血液，以及屠宰场猪血液）与新鲜人血进行了比较。
为了考虑个体供体和物种之间的血液凝固性差异，在动态流动回路系统中测试之前，立即将每个血液池肝素化至供体特异性浓度。使用静态血栓形成预测试确定目标肝素水平。对于动态测试，将全血在室温下以 200ml/min 的速度通过包含单个测试材料的流动回路再循环 1 小时。研究了四种具有不同血栓形成潜力的材料：乳胶（阳性对照）、聚四氟乙烯（PTFE）（阴性对照）、硅酮（中间血栓形成潜力）和高密度聚乙烯（HDPE）（历史上抗血栓形成）。定量测定测试材料上的血栓重量和表面积覆盖范围，以及血液中的血小板计数减少。
虽然不同血液来源之间的供体特异性肝素水平从 0.6U/ml 到 7.0U/ml 变化很大，但每种来源都能够区分血栓形成的乳胶和抗血栓形成的 PTFE 和 HDPE 材料（p<0.05）。然而，只有供体绵羊和牛血液足够敏感，可以区分中间血栓形成的硅酮材料与 PTFE 和 HDPE 相比的反应增加。
这些结果表明，当使用适当的对照材料和供体特异性抗凝水平时，多种动物血液来源（特别是供体绵羊和牛血液）可能是替代新鲜人血进行动态血栓形成性测试的合适替代品。
