Thermodynamics of Gelation and Dynamic Properties of Biosynthetic Hydrogels

生物合成水凝胶的凝胶化热力学和动态特性

• 批准号: 7407220
• 负责人: Bradley David Olsen
• 金额: $ 4.48万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7407220
• 关键词: Adverse effects; Affect; Amino Acid Sequence; Anabolism; Benchmarking; Binding; Biocompatible; Biocompatible Materials; Biological; Biological Process; Cell Adhesion; Cells; Cereals; Chemicals; Diffusion; Dose; Drug Controls; Drug Delivery Systems; Gel; Hydrogels; Left; Leucine Zippers; Light; Link; Location; Mechanics; Modeling; Molecular Weight; Nucleic Acids; Object Attachment; Peptide Sequence Determination; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physics; Physiological; Pliability; Polymers; Property; Proteins; Rate; Research; Solid; Specificity; Stem cells; Structure; Swelling; System; Techniques; Technology; Theoretical model; Therapeutic; Thermodynamics; Time; Tissue Engineering; Tissues; Water; base; biomaterial compatibility; controlled release; copolymer; crosslink; design; drug structure; human tissue; insight; interest; physical property; protein structure; research study; self assembly; soft tissue; theories; tissue support frame

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.

用于药物输送和组织工程的生物材料的合理设计需要一个基本原理 了解这些材料的结构-性能关系，包括通过 介质、机械性能和热力学转变可用于生产 环保材料。水凝胶生物材料具有响应性的独特优势 溶胀和溶胶/凝胶转变、可注射性以及装载大分子药物疗法的灵活性。 基于蛋白质的水凝胶由于其生物相容性而作为生物材料特别有吸引力， 生物降解性和固有的生物功能。生产物理蛋白质凝胶的简单方法 采用蛋白质三嵌段共聚物与亮氨酸拉链末端嵌段形成物理交联和柔性 聚电解质中间嵌段。该项目将利用理论和实验来阐明基本原理 控制这些凝胶的结构-性质关系。蛋白质聚合物将通过生物合成来制备 利用生物材料中提供的明确序列特异性的技术。这 这些材料的动力学特性将作为交联价、分子量、 链的灵活性和交联强度来阐明关键的结构-性能关系。粗粒度的 将开发理论模型并参数化。使用实验的输入，该模型将 进行完善，模型的预测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。粗略训练方法 所采用的方法将使许多结果能够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理。 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，具有生物降解性和 修改它们以执行生物学功能的容易程度。该项目将开发一个 了解蛋白质序列和凝胶结构如何影响蛋白质水凝胶的特性， 使它们能够针对药物输送和组织工程进行优化。