Fallon Meghan E, Le Hillary H, Bates Novella M, Yao Yuan, Yim Evelyn K F, Hinds Monica T, Anderson Deirdre E J
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, United States.
Department of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada.
Front Physiol. 2022 Sep 19;13:983187. doi: 10.3389/fphys.2022.983187. eCollection 2022.
Small-diameter synthetic vascular grafts that have improved hemocompatibility and patency remain an unmet clinical need due to thrombosis. A surface modification that has potential to attenuate these failure mechanisms while promoting an endothelial layer is the micropatterning of luminal surfaces. Anisotropic features have been shown to downregulate smooth muscle cell proliferation, direct endothelial migration, and attenuate platelet adhesion and activation. However, the effect of micropatterning feature size and orientation relative to whole blood flow has yet to be investigated within a systematic study. In this work, hemocompatibility of micropattern grating sizes of 2, 5, and 10 µm were investigated. The thrombogenicity of the micropattern surface modifications were characterized by quantifying FXIIa activity, fibrin formation, and static platelet adhesion . Additionally, dynamic platelet attachment and end-point fibrin formation were quantified using an established, flowing whole blood non-human primate shunt model without antiplatelet or anticoagulant therapies. We observed a higher trend in platelet attachment and significantly increased fibrin formation for larger features. We then investigated the orientation of 2 µm gratings relative to whole blood flow and found no significant differences between the various orientations for platelet attachment, rate of linear platelet attachment, or end-point fibrin formation. MicroCT analysis of micropatterned grafts was utilized to quantify luminal patency. This work is a significant step in the development of novel synthetic biomaterials with improved understanding of hemocompatibility for use in cardiovascular applications.
由于血栓形成，具有改善的血液相容性和通畅性的小直径合成血管移植物仍然是未满足的临床需求。一种有可能减弱这些失败机制同时促进内皮层形成的表面修饰方法是对管腔表面进行微图案化。已表明各向异性特征可下调平滑肌细胞增殖、引导内皮细胞迁移，并减弱血小板黏附和活化。然而，在一项系统性研究中，微图案特征尺寸和相对于全血流的方向的影响尚未得到研究。在这项工作中，研究了2、5和10微米的微图案光栅尺寸的血液相容性。通过量化因子XIIa活性、纤维蛋白形成和静态血小板黏附来表征微图案表面修饰的血栓形成倾向。此外，使用已建立的、流动全血的非人类灵长类动物分流模型，在不使用抗血小板或抗凝治疗的情况下，对动态血小板黏附和终点纤维蛋白形成进行了量化。我们观察到较大特征的血小板黏附有更高的趋势，并且纤维蛋白形成显著增加。然后，我们研究了2微米光栅相对于全血流的方向，发现不同方向在血小板黏附、线性血小板黏附率或终点纤维蛋白形成方面没有显著差异。利用微图案化移植物的显微CT分析来量化管腔通畅性。这项工作是开发新型合成生物材料的重要一步，有助于更好地理解用于心血管应用的血液相容性。
