ARTIFICIAL EXTRACELLULAR MATRIX PROTEINS FOR VASCULAR GR

这项工作的长期目标是开发新的基因工程材料，用于制造具有改善长期通畅性的血管移植物。这种方法是基于以下假设的：i)。现有的人造血管移植材料--特别是膨体聚四氟乙烯(EPTFE)和涤纶--无论是在表面化学方面还是在机械性能方面都不是最优的，ii)。合成移植物的愈合机制至少部分由细胞与移植物表面或与沉积在该表面的大分子，包括血浆蛋白或细胞外基质(ECM)蛋白的相互作用所控制，三)。通过呈现特定细胞表面受体的配体，可以获得对移植物表面细胞行为的控制的措施，以及iv)。这种ECM蛋白质的工程变体将允许控制移植物的关键机械性能和移植物表面的配体呈现。该项目将包括：i)。编码含有特定细胞结合域和交联域的人造ECM蛋白的人工基因的微生物表达，ii)。由这些蛋白质制备的交联膜的制备和力学特性，III)。测定这些表面对在生理相关剪应力下培养的内皮细胞的粘附性，以及iv)。培养在人工细胞外基质上的内皮细胞单层的行为分析。

The long-term objective of this work is the development of new genetically engineered materials to be used in the fabrication of vascular grafts characterized by improving long-term patency. The approach is predicated on the following hypotheses: i). that existing synthetic vascular graft materials - specifically expanded polytetrafluoroethylene (ePTFE) and Dacron - are not optimal, either in terms of surface chemistry or with respect to mechanical properties, ii). that the mechanisms of healing of synthetic grafts are controlled at least in part by cellular interactions with the graft surface or with macromolecules, including plasma proteins or extracellular matrix (ECM) proteins, deposited on that surface, iii). that a measure of control of cellular behavior at the graft surface can be gained by presentation of ligands for specific cell- surface receptors, and iv). that engineered variants of ECM proteins will allow control, both of the key mechanical properties of the graft, and of the presentation of ligands at the graft surface. The project will include: i). microbial expression of artificial genes encoding artificial ECM proteins that incorporate specific cell-binding and crosslinking domains, ii). fabrication and mechanical characterization of crosslinked films prepared from these proteins, iii). determination of the adhesivity of these surfaces with respect to endothelial cells cultured under physiologically relevant shear stresses, and iv). analysis of the behavior of endothelial cell monolayers cultured on artificial extracellular matrices.