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，它们通常会引发以蛋白质为基础的反应，目的是中和异物。人们发现在合成材料上涂上聚合物可以抵抗其中一些排斥反应，但这种做法并不总是成功的，也没有得到很好的理解。我们建议对两种类型的此类系统进行基础研究：使用聚合物刷的材料涂层和使用超支化聚合物作为白蛋白替代品或药物载体。刷是一种聚合物，它们从一个初始表面生长得如此紧密，以至于它们被迫形成一个更大的结构，而不是在没有邻近表面约束的情况下。刷子被认为对试图穿透它们的蛋白质是排斥的，但我们发现这通常是不正确的，并提出了基础研究来理解这个谜题。超支化聚合物的作用有点像蛋白质，因为它们的溶液结构紧凑。每个分支的末端都有一个反应性基团，可以衍生以增强小分子的结合或添加短的线性聚合物链，从而提供对免疫系统的保护。脂肪酸的疏水结合对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，从而为细胞提供更局部的结合物种来源。

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.