Cardiovascular Innovation Institute, University of Louisville and Jewish Hospital, Louisville, Kentucky, USA.
J Biomed Mater Res A. 2012 Dec;100(12):3189-96. doi: 10.1002/jbm.a.34256. Epub 2012 Jun 15.
Endovascular stent grafts used for treatment of arterial aneurysms require preclinical testing for investigation of biological responses following implantation. The preclinical evaluation process related to the safety and efficacy of these devices is limited by the absence of an in vitro aneurysmal blood vessel equivalent capable of providing high-throughput, cost-effective assessments. With this in mind, the focus of this work was to develop an aneurysm model consisting of human blood vessel cells. To create aneurysmal scaffolds, expanded polytetrafluoroethylene vascular grafts were dilated utilizing an angioplasty balloon. Stromal vascular fraction cells isolated from human adipose tissue were integrated with the scaffolds, and luminal flow of nutrient medium was executed for 14 days in a vascular bioreactor. Following bioreactor perfusion, histology verified that a neointimal lining of human tissue had formed. Immunohistochemistry and scanning electron microscopy revealed a flow-contacting layer of smooth muscle cells, characterizing the model as a representation of neointimal formation in an injured or diseased vessel. This study has demonstrated the engineering of a vascular construct containing an aneurysmal dilation. A tissue-engineered aneurysm model could provide an alternative to current nonbiological in vitro aneurysm models and serve as a practical tool in the progression of new devices toward in vivo studies.
用于治疗动脉动脉瘤的血管内支架移植物需要进行临床前测试，以研究植入后的生物学反应。这些设备的安全性和有效性的临床前评估过程受到缺乏能够提供高通量、具有成本效益评估的体外动脉瘤血管等效物的限制。考虑到这一点，这项工作的重点是开发一种由人血管细胞组成的动脉瘤模型。为了创建动脉瘤支架，利用血管成形球囊扩张膨体聚四氟乙烯血管移植物。从人脂肪组织中分离出基质血管成分细胞，并在血管生物反应器中进行 14 天的腔流营养培养基。生物反应器灌注后，组织学证实已形成人类组织的新生内膜。免疫组织化学和扫描电子显微镜显示出与血流接触的平滑肌细胞层，将该模型表征为损伤或患病血管中新生内膜形成的代表。这项研究展示了一种包含动脉瘤扩张的血管构建物的工程设计。组织工程化的动脉瘤模型可以替代当前的非生物体外动脉瘤模型，并作为新设备向体内研究进展的实用工具。
