Cardinal Kristen O'Halloran, Bonnema Garret T, Hofer Heidi, Barton Jennifer Kehlet, Williams Stuart K
Biomedical Engineering Program, University of Arizona, Tucson, Arizona 85724-5084, USA.
Tissue Eng. 2006 Dec;12(12):3431-8. doi: 10.1089/ten.2006.12.3431.
The accelerating use of minimally invasive procedures for the treatment of cardiovascular disease, and the commensurate development of intravascular devices such as stents, has lead to a high demand for preclinical assessment techniques. A 3-dimensional in vitro blood vessel mimic (BVM) would be ideal for device testing before animal or clinical studies. This is possible based on current capabilities for the creation of tissue-engineered vascular grafts (TEVGs). Using an established method of pressure-sodding human endothelial cells onto a polymer scaffold, a BVM was created in an in vitro bioreactor system under flow. Scanning electron microscopy and immunohistochemistry verified a cellular lining and revealed a luminal monolayer of endothelial cells. After BVM development, bare metal stents were deployed. Stented and unstented BVMs were evaluated using fluorescent nuclear staining and optical coherence tomography (OCT). En face and cross-sectional evaluation of bisbenzimide-stained nuclei revealed cellular coverage of the stent surfaces. Cross-sectional evaluation using OCT also illustrated a cellular layer developing over the stent struts. These data support the use of TEVGs as in vitro BVMs for pre-clinical evaluation of the endothelial cell response to stents and endovascular devices.
用于治疗心血管疾病的微创程序的加速应用,以及诸如支架等血管内装置的相应发展,导致对临床前评估技术的高需求。三维体外血管模拟物(BVM)对于在动物或临床研究之前进行装置测试将是理想的。基于目前创建组织工程血管移植物(TEVG)的能力,这是可行的。使用一种将人内皮细胞压力接种到聚合物支架上的既定方法,在流动条件下的体外生物反应器系统中创建了一个BVM。扫描电子显微镜和免疫组织化学证实了细胞内衬,并揭示了内皮细胞的管腔单层。在BVM形成后,部署了裸金属支架。使用荧光核染色和光学相干断层扫描(OCT)对带支架和不带支架的BVM进行评估。对双苯甲酰亚胺染色的细胞核进行的正面和横截面评估显示了支架表面的细胞覆盖情况。使用OCT进行的横截面评估也表明在支架支柱上形成了细胞层。这些数据支持将TEVG用作体外BVM,用于对内皮细胞对支架和血管内装置的反应进行临床前评估。