Enhanced Endothelial Cell Seeding On Vascular Grafts

增强血管移植物上的内皮细胞接种

• 批准号: 6789512
• 负责人: William D Timmons
• 金额: $ 23.72万
• 依托单位: ENTERATECH, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-10 至 2007-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789512
• 关键词: apical membrane; cardiovascular transplantation; cell adhesion; cell morphology; cell transplantation; electrical property; human tissue; method development; shear stress; surface coating; surface property; tissue /cell culture; vascular endothelium

DESCRIPTION (provided by applicant): Over 65% of small and medium sized synthetic vascular grafts occlude within 5 years of implantation. It has long been known that coating the luminal surface with endothelial cells (EC's) prior to implantation significantly extends the life of the graft, yet no commercially viable clinical systems have been developed. The goal of this work is to develop a commercially viable method of endothelializing the luminal surface of synthetic vascular grafts based on the electrostatic seeding method. The electrostatic method accomplishes implantation by temporarily altering the prosthetic graft lumenal surface charge to a more positive state, which results in an increased total number of adhered and flattened EC's compared to other methods. The flattened phase is important because it minimizes the loss of EC's upon exposure to fluid shear stress. Electrostatic seeding is rapid, taking only 16 minutes compared to days for the gravitational seeding method. The original electrostatic technique works well for relatively short grafts (<15cm), but presents severe limitations for longer grafts and commercial packaging systems. Our enhanced method promises to retain all of the advantages of the original technique while also overcoming the graft length restrictions and packaging issues. Testing will demonstrate that these improvements apply equally well to short (6cm) and long (80cm) e-PTFE grafts, and will result in the same seeding densities as the original technique. Tests will also demonstrate that the enhanced technique results in the same short seeding times, high cell viability, high degree of maturation (flattening), and low degree of cellular damage. In addition, tests using physiologic shear flow conditions (15 dynes/cm2) will demonstrate that, independent of graft length, the EC's are retained on the graft walls equally as well as the original technique. Key Words: electrostatic cell seeding, synthetic vascular graft, endothelial cells, human umbilical vein endothelial cells, expanded polytetrafluoroethylene (ePTFE).

描述(由申请人提供)： 超过65%的中小型人造血管在植入后5年内闭塞。人们早就知道，在植入前在管腔表面涂覆内皮细胞(EC)可以显著延长移植物的寿命，但目前还没有开发出商业上可行的临床系统。这项工作的目标是开发一种商业上可行的方法，以静电播种法为基础，内皮化人工血管的管腔表面。静电法通过暂时改变假体腔表面电荷到更正的状态来完成植入，这导致与其他方法相比，粘连和扁平的EC的总数增加。扁平的相很重要，因为它最大限度地减少了暴露在流体剪应力下的EC的损失。静电播种速度很快，只需16分钟，而重力播种法只需数天。最初的静电技术适用于相对较短的嫁接(&lt；15厘米)，但对较长的嫁接和商业包装系统存在严重限制。我们改进的方法承诺保留原始技术的所有优势，同时也克服了移植物长度限制和包装问题。测试将证明，这些改进同样适用于短(6厘米)和长(80厘米)的e-PTFE移植物，并将产生与原始技术相同的播种密度。试验还将证明，增强的技术同样可以缩短播种时间、提高细胞存活率、提高成熟度(扁平化)和降低细胞损伤程度。此外，使用生理剪切流条件(15dynes/cm2)的测试将证明，EC与移植物长度无关，与原始技术一样保留在移植物壁上。关键词：静电细胞接种，人造血管移植，内皮细胞，人脐静脉内皮细胞，膨体聚四氟乙烯。