Development, analysis and application of biocompatible polymers

当合成材料暴露于血液或注射到动物体内时，它们通常会引起旨在中和异物的蛋白质反应。 已经发现用聚合物涂覆合成材料可以抵抗这些排斥反应中的一些，但是实践并不是一致成功的，也不是很好理解的。 我们建议对两种类型的这种系统进行基础研究：用聚合物刷涂覆材料和使用超支化聚合物作为白蛋白替代品或药物载体。 刷是从初始表面生长的如此紧密的聚合物，使得它们被迫形成比如果不受其相邻表面约束的话所采取的更延伸的构型。 刷预计是排斥蛋白质试图穿透他们，但我们发现这是不普遍的，并提出基础研究，以提供理解这一难题。 超支化聚合物由于其紧凑的溶液构型而有点像蛋白质。 每个分支以反应性基团结束，该反应性基团可以被衍生化以增强小分子的结合或添加短的线性聚合物链以提供对免疫系统的保护。脂肪酸的疏水结合对于白蛋白模拟物是特别重要的，因此我们建议对这种反应进行详细的研究。 我们还将研究这些材料如何与细胞表面相互作用，以及如何增强这种相互作用，为细胞提供更多的结合物种来源。

When synthetic materials are exposed to blood or injected into an animal they generally elicit protein-based reactions aimed at neutralizing the foreign body.  Coating the synthetic material with polymers has been found to resist some of these rejection reactions, but the practice is not uniformly successful nor well understood.  We are proposing fundamental studies on two types of such systems: coatings of materials with polymer brushes and the use of hyperbranched polymers as albumin substitutes or drug carriers.  Brushes are polymers grown so close together from an initiating surface that they are forced into a more extended configuration than they would take up if not constrained by their neighbours.  Brushes are expected to be repulsive to proteins trying to penetrate them but we have found this is not generally true and propose basic studies to provide understanding of this puzzle.  Hyperbranched polymers act somewhat like proteins because of their compact solution configuration.  Each branch ends in a reactive group that can be derivatized to enhance binding of small molecules or to add short linear polymer chains that provide protection from the immune system. Hydrophobic binding of fatty acids is particularly important for an albumin mimic so we propose detailed studies of this kind of reaction.  We will also study how these materials interact with cell surfaces and how such interactions could be enhanced to provide a more local source of the bound species to cells.