Biomedical Engineering Department, Northwestern University, Evanston, IL 60208, USA.
Biomaterials. 2013 Jan;34(1):30-41. doi: 10.1016/j.biomaterials.2012.09.046. Epub 2012 Oct 12.
Prosthetic vascular grafts do not mimic the antithrombogenic properties of native blood vessels and therefore have higher rates of complications that involve thrombosis and restenosis. We developed an approach for grafting bioactive heparin, a potent anticoagulant glycosaminoglycan, to the lumen of ePTFE vascular grafts to improve their interactions with blood and vascular cells. Heparin was bound to aminated poly(1,8-octanediol-co-citrate) (POC) via its carboxyl functional groups onto POC-modified ePTFE grafts. The bioactivity and stability of the POC-immobilized heparin (POC-Heparin) were characterized via platelet adhesion and clotting assays. The effects of POC-Heparin on the adhesion, viability and phenotype of primary endothelial cells (EC), blood outgrowth endothelial cells (BOECs) obtained from endothelial progenitor cells (EPCs) isolated from human peripheral blood, and smooth muscle cells were also investigated. POC-Heparin grafts maintained bioactivity under physiologically relevant conditions in vitro for at least one month. Specifically, POC-Heparin-coated ePTFE grafts significantly reduced platelet adhesion and inhibited whole blood clotting kinetics. POC-Heparin supported EC and BOEC adhesion, viability, proliferation, NO production, and expression of endothelial cell-specific markers von Willebrand factor (vWF) and vascular endothelial-cadherin (VE-cadherin). Smooth muscle cells cultured on POC-Heparin showed increased expression of α-actin and decreased cell proliferation. This approach can be easily adapted to modify other blood contacting devices such as stents where antithrombogenicity and improved endothelialization are desirable properties.
人工血管移植物不能模拟天然血管的抗血栓特性，因此并发症发生率更高，包括血栓形成和再狭窄。我们开发了一种将生物活性肝素（一种有效的抗凝糖胺聚糖）接枝到 ePTFE 血管移植物内腔的方法，以改善其与血液和血管细胞的相互作用。肝素通过其羧基官能团与氨基化聚（1,8-辛二醇-共-柠檬酸）（POC）结合到 POC 修饰的 ePTFE 移植物上。通过血小板黏附实验和凝血实验对 POC 固定肝素（POC-Heparin）的生物活性和稳定性进行了表征。还研究了 POC-Heparin 对来源于人外周血内皮祖细胞（EPC）的原代内皮细胞（EC）、血源性内皮细胞（BOEC）以及平滑肌细胞黏附、活力和表型的影响。POC-Heparin 移植物在体外生理相关条件下至少一个月内保持生物活性。具体而言，POC-Heparin 涂层的 ePTFE 移植物显著减少了血小板黏附，并抑制了全血凝血动力学。POC-Heparin 支持 EC 和 BOEC 的黏附、活力、增殖、NO 产生以及内皮细胞特异性标志物 von Willebrand 因子（vWF）和血管内皮钙黏蛋白（VE-cadherin）的表达。在 POC-Heparin 上培养的平滑肌细胞表现出α-肌动蛋白表达增加和细胞增殖减少。这种方法可以很容易地适应修饰其他接触血液的装置，如支架，在这些装置中，抗血栓形成和改善内皮化是理想的特性。
