Development, analysis and application of biocompatible polymers

当合成材料暴露在血液中或注射到动物体内时，它们通常会引发基于蛋白质的反应，旨在中和异物。人们已经发现，在合成材料上涂上聚合物可以抵抗其中的一些排斥反应。但这种做法并不总是成功的，也没有得到很好的理解。我们正在提议对两种类型的此类系统进行基础研究：用聚合物刷子覆盖材料，以及使用超支化聚合物作为白蛋白替代品或药物载体。超支化聚合物是从引发表面生长起来的聚合物，它们离引发表面非常近，以至于它们被强迫进入更广泛的构型，如果它们不受邻居限制的话。它们被认为是对试图穿透它们的蛋白质的排斥，但我们发现这种情况并不普遍，并建议进行基础研究，以了解这个谜题。超支化聚合物的行为有点像蛋白质由于其紧凑的溶液配置，每个支链末端都是一个反应基团，可以衍生化以增强小分子的结合或添加提供免疫系统保护的短线状聚合物链。脂肪酸的疏水结合对于白蛋白模拟物特别重要，因此我们建议对这种反应进行详细研究。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，以向细胞提供更本地的结合物种来源。

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.