Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio; Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio.
Ann Thorac Surg. 2021 Apr;111(4):1234-1241. doi: 10.1016/j.athoracsur.2020.06.112. Epub 2020 Sep 16.
Small diameter (<6 mm), bioabsorbable, arterial, tissue-engineered vascular grafts (TEVGs) remain limited by thromboembolism. The objective of this study was to test whether heparin-eluting (HE) TEVGs prevent early thrombosis in a large animal model.
TEVGs were created with an outer poly-ε-caprolactone electrospun nanofiber layer, with a 15-μm average pore size and an inner layer composed of a 50:50 poly(L-lactide-co-ε-caprolactone) copolymer. Adult female sheep (n = 5) underwent bilateral carotid artery interposition grafting, with a control TEVG in 1 carotid artery and an HE TEVG in the contralateral position. Animals were followed for 8 weeks with weekly Duplex ultrasonography to monitor TEVG performance.
All sheep survived to the designated endpoint. At 8 weeks all 5 HE TEVGs were patent. Three of 5 control TEVGs had early thrombotic occlusion at <1 week. More than 97% of heparin release occurred within the first 24 hours. Histologic evaluation of the HE TEVG displayed cellularity like a native carotid artery with no evidence of calcification. Significantly fewer platelets adhered to the HE TEVG than to the control TEVG (P < .001).
This study suggests HE TEVGs prevent acute graft thrombosis. We hypothesize that the HE properties of the HE TEVG during vascular endothelialization is useful for maintaining TEVG patency. This technique may aid in the translation of small arterial TEVGs to the clinic.
小直径（<6 毫米）、可生物吸收、动脉、组织工程血管移植物（TEVG）仍然受到血栓栓塞的限制。本研究的目的是检验肝素洗脱（HE）TEVG 是否能预防大型动物模型中的早期血栓形成。
TEVG 采用聚己内酯电纺纳米纤维外层构建，平均孔径为 15μm，内层由 50:50 聚（L-丙交酯-co-ε-己内酯）共聚物组成。成年雌性绵羊（n=5）接受双侧颈总动脉间置移植术，其中一侧颈总动脉置入对照 TEVG，对侧置入 HE TEVG。每周通过双功超声检查监测 TEVG 性能，对动物进行 8 周的随访。
所有绵羊均存活至指定的终点。在第 8 周，5 个 HE TEVG 均通畅。5 个对照 TEVG 中有 3 个在<1 周时发生早期血栓闭塞。超过 97%的肝素在 24 小时内释放。HE TEVG 的组织学评估显示出类似于天然颈动脉的细胞活力，没有钙化的证据。与对照 TEVG 相比，HE TEVG 上黏附的血小板明显更少（P<0.001）。
本研究表明 HE TEVG 可预防急性移植物血栓形成。我们假设 HE TEVG 在血管内皮化期间的 HE 特性有助于维持 TEVG 通畅。这项技术可能有助于将小口径动脉 TEVG 转化为临床应用。
