Engineering enhancement of endothelial cell retention on arterial substitutes

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。基于生物材料的动脉重建是治疗动脉粥样硬化的有效方法，动脉粥样硬化是人类死亡的主要原因。然而，生物材料会引起血栓形成和内膜增生，导致重建动脉衰竭的血管疾病。虽然将内皮细胞植入动脉替代物被认为是预防这些疾病的潜在方法，但内皮细胞经常与动脉替代物分离。因此，动脉重建的一个重要问题是增强内皮细胞在动脉替代物上的保留。本研究的目的是建立一种分子工程方法来增强内皮细胞保留，减少血栓形成和内膜增生，并提高动脉代用品的性能。本研究主要集中在两个特定目的：通过sirna介导的粘附抑制分子抑制生物基质支架和聚四氟乙烯基动脉替代品增强内皮细胞保留，并在大鼠动脉重建模型中测试该方法的有效性。此外，我们建议在生物医学工程课程中应用“实验室-讲座整合”的理念，以改善教育技术。这项研究的智力价值源于这样一个事实，即拟议的工作可能通过使用新技术来改善重建动脉的性能，为人类动脉疾病治疗方法的发展提供基础信息。本研究将在以下几个方面产生广泛的影响。首先，考虑到重建动脉的高失败率，本研究的结果可能会使大量患者受益。其次，生物医学科学和生物工程研究者之间的跨学科合作将扩大拟议研究的影响，并促进工程与生命科学在研究和教育中的整合。第三，本研究将通过将研究成分和实验室实验整合到讲座主题中，为改进生物工程教育技术提供信息，这种方法可能通过本科和研究生教育影响未来的科学和非科学社区。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)0932131LiuBiomaterial-based arterial reconstruction is an effective approach for the treatment of atherosclerosis, the leading cause of human death. However, biomaterials induce thrombosis and intimal hyperplasia, vascular disorders contributing to the failure of reconstructed arteries. While seeding endothelial cells to arterial substitutes is considered a potential approach for preventing these disorders, endothelial cells often detach from the arterial substitute. Thus, an important issue in arterial reconstruction is to enhance the retention of endothelial cells on arterial substitutes. The objective of the proposed research is to establish a molecular engineering approach to enhance endothelial cell retention, reduce thrombosis and intimal hyperplasia, and improve the performance of arterial substitutes. This investigation is focused on two specific aims: enhance endothelial cell retention on biological matrix scaffold- and polytetrafluoroethylene-based arterial substitutes by siRNA-mediated suppression of adhesion-inhibiting molecules, and test the effectiveness of this approach in a rat model of arterial reconstruction. In addition, we propose to improve education technologies by applying the "lab-lecture integration" concept to biomedical engineering curriculum. The intellectual merit of this research stems from the fact that the proposed work may improve the performance of reconstructed arteries by using novel technologies, providing fundamental information for the development of therapeutic approaches for human arterial disorders. This research will exert broad impacts in the following aspects. First, given the high failure rate of reconstructed arteries, results from this research may potentially benefit a large number of patients. Second, the cross-disciplinary collaboration between investigators in biomedical science and bioengineering will broaden the impact of the proposed research and facilitate engineering-life science integration in research and education. Third, this investigation will provide information for improving bioengineering education technologies by integrating research components and lab experiments into lecture topics, an approach potentially influencing future scientific and non-scientific communities through undergraduate and graduate education.