Department of Chemical and Biological Engineering, Women and Children's Hospital of Buffalo, N.Y., USA.
Cells Tissues Organs. 2012;195(1-2):108-21. doi: 10.1159/000331415. Epub 2011 Oct 14.
The major objective of successful development of tissue-engineered vascular grafts is long-term in vivo patency. Optimization of matrix, cell source, surface modifications, and physical preconditioning are all elements of attaining a compatible, durable, and functional vascular construct. In vitro model systems are inadequate to test elements of thrombogenicity and vascular dynamic functional properties while in vivo implantation is complicated, labor-intensive, and cost-ineffective. We proposed an ex vivo ovine arteriovenous shunt model in which we can test the patency and physical properties of vascular grafts under physiologic conditions. The pressure, flow rate, and vascular diameter were monitored in real-time in order to evaluate the pulse wave velocity, augmentation index, and dynamic elastic modulus, all indicators of graft stiffness. Carotid arteries, jugular veins, and small intestinal submucosa-based grafts were tested. SIS grafts demonstrated physical properties between those of carotid arteries and jugular veins. Anticoagulation properties of grafts were assessed via scanning electron microscopy imaging, en face immunostaining, and histology. Luminal seeding with endothelial cells greatly decreased the attachment of thrombotic components. This model is also suture free, allowing for multiple samples to be stably processed within one animal. This tunable (pressure, flow, shear) ex vivo shunt model can be used to optimize the implantability and long-term patency of tissue-engineered vascular constructs.
成功开发组织工程血管移植物的主要目标是长期体内通畅性。优化基质、细胞来源、表面修饰和物理预处理都是实现相容、持久和功能血管构建体的要素。体外模型系统不足以测试血栓形成性和血管动态功能特性的元素，而体内植入则复杂、劳动密集且成本效益低。我们提出了一种羊的动静脉外分流模型，我们可以在生理条件下测试血管移植物的通畅性和物理特性。实时监测压力、流速和血管直径，以评估脉搏波速度、增强指数和动态弹性模量，这些都是移植物僵硬度的指标。测试了颈动脉、颈静脉和基于小肠黏膜下层的移植物。SIS 移植物的物理特性介于颈动脉和颈静脉之间。通过扫描电子显微镜成像、全面免疫染色和组织学评估移植物的抗凝特性。腔内内皮细胞播种大大减少了血栓成分的附着。该模型还无缝线，允许在一只动物内稳定处理多个样本。这种可调（压力、流量、剪切）的体外分流模型可用于优化组织工程血管构建体的可植入性和长期通畅性。
