Thermodynamics of Gelation and Dynamic Properties of Biosynthetic Hydrogels

合理设计用于药物输送和组织工程的生物材料需要一个基本的 了解这些材料中的结构-性能关系，包括通过 介质，机械性能和热力学转变，可以被利用来产生 环保材料。水凝胶生物材料提供了响应的独特优势 溶胀和溶胶/凝胶转变、可注射性和加载大分子药物疗法的灵活性。 基于蛋白质的水凝胶作为生物材料特别有吸引力，因为它们的生物相容性， 生物降解性和固有的生物功能。一种生产物理蛋白质凝胶的简单方法 采用带有亮氨酸拉链末端嵌段的蛋白质三嵌段共聚物形成物理交联剂和柔性 聚电解质中间块。本课题将运用理论和实验相结合的方法，阐明 支配这些凝胶的结构-性质关系。将利用生物合成技术制备蛋白质聚合物 利用生物材料中提供的明确序列特异性的技术。这个 这些材料的动力学性质将作为交联价，分子量， 链的柔韧性和交联度，以阐明关键的结构-性质关系。粗粒度的 理论模型将被开发和参数化。使用来自实验的输入，该模型将 模型的预测结果将用于指导具有性能的凝胶的合成 针对组织工程或药物输送中的特定应用。粗略排除法 所采用的将允许许多结果被推广到特定的实验系统之外， 深入了解一般水凝胶系统的设计原则。 蛋白质水凝胶是一种有趣的生物材料，因为它们与人体组织相似，可生物降解性，以及 它们可以很容易地被改造以执行生物功能。该项目将开发一种 了解蛋白质序列和凝胶结构如何影响蛋白质水凝胶的性质， 从而使它们在药物输送和组织工程方面得到优化。

Rational design of biomaterials for drug delivery and tissue engineering requires a fundamental understanding of the structure-property relationships in these materials, including diffusion through the medium, the mechanical properties, and thermodynamic transitions that may be exploited to produce environmentally responsive materials. Hydrogel biomaterials offer the unique advantages of responsive swelling and sol/gel transitions, injectability, and flexibility in loading with macromolecular drug therapies. Protein-based hydrogels are particularly attractive as biomaterials because of their biocompatibility, biodegradability, and inherent biofunctionality. A simple approach to produce physical protein gels employs protein triblock copolymers with leucine zipper endblocks to form physical crosslinks and flexible polyelectrolyte midblocks. Using both theory and experiment, this project will elucidate the fundamental structure-property relationships governing these gels. Protein polymers will be prepared using biosynthetic techniques to take advantage of the explicit sequence specificity offered in biological materials. The dynamical properties of these materials will be studied as a function of crosslink valency, molecular weight, chain flexibility, and crosslink strength to elucidate key structure-property relationships. A coarse-grained theoretical model will be developed and parameterized. Using input from the experiments, this model will be refined, and the predictions of the model will be used to guide the synthesis of gels with properties targeted at specific applications in tissue engineering or drug delivery. The coarse-xjrainingapproach employed will allow many of the results to be generalized beyond the specific experimental system, providing insight into the design principles of general hydrogel systems. Protein hydrogels are interesting biomaterials due to their similarity to human tissue, biodegradability, and the ease with which they can be modified to perform a biological function. This project will develop an understanding of how the protein sequence and gel structure affect the properties of protein hydrogels, allowing them to be optimized for drug delivery and tissue engineering.