Hydrogels from Designed Peptides

描述（由申请人提供）：通过肽自组装制备水凝胶，可以通过设计单个组成分子来定义最终的生物材料特性。化学功能、材料形态、粘弹性和可加工性可以在自组装系统的分子水平上进行设计。在这里，肽被设计成分子内折叠以响应外部刺激，形成能够自组装的β -发夹构象。折叠的发夹组装成稀但刚性的水凝胶，在纳米到微观尺度上表现出孔隙。触发折叠允许在时间和空间上控制材料的形成。凝胶会被各种生理相关刺激触发；例如pH值，盐，钙离子，温度和光。化学良性折叠/自组装策略，以及合成的水凝胶固有的肽性质，为成纤维细胞和成骨细胞提供了潜在的组织工程底物。通过直接观察肽结构如何影响自组装过程、材料形态、材料性质和细胞相容性，可以确定肽设计原则，从而产生能够支持细胞粘附和增殖的刚性、多孔水凝胶。跨学科的“从分子到材料”的设计和拟建的水化体系的特性表征将通过化学/生物化学和材料科学与工程部门之间的密切合作来完成。本研究工作将：1。获得折叠和自组装过程导致水凝胶的形成和分子设计如何影响材料性能的基本理解。2. 通过设计活性分子内折叠触发器，增强基于发夹的水凝胶的可加工性，该触发器允许肽溶液在提示时进行水凝胶化。

DESCRIPTION (provided by applicant): The preparation of hydrogels via peptide self-assembly allows one to define ultimate biomaterial properties by design of individual constituent molecules. Chemical functionality, material morphology, viscoelasticity and processibility can be designed at the molecular level of a self-assembling system. Herein, peptides are designed to intramolecularly fold in response to external stimuli into beta-hairpin conformations that are capable of self-assembling. Folded hairpins assemble into dilute but rigid hydrogels exhibiting porosity on the nano- to -microscale. Triggered folding allows temporal and spatial control of material formation. Gelation will be triggered by various physiologically relevant stimuli; e.g. pH, salt, calcium ions, temperature and light. The chemically benign folding/self-assembly strategy, and the inherent peptidic nature of the resultant hydrogels, provide a potential tissue engineering substrate for fibroblasts and osteoblasts. Peptide design principles leading to rigid, porous hydrogels capable of supporting cell adhesion and proliferation will be determined by directly observing how peptide structure affects the self-assembly process, material morphology, material properties and cytocompatibility. The interdisciplinary "molecular to materials" design and properties characterization of the proposed hydrogelation system will be accomplished via close collaboration between the chemistry/biochemistry and materials science and engineering departments. This research effort will: 1. Gain a fundamental understanding of the folding and self-assembly process leading to hydrogel formation and how molecular design affects material properties. 2. Enhance the processibility of hairpin-based hydrogels by designing active intramolecular folding triggers that allow peptide solutions to undergo hydrogelation on cue. 3. Determine how peptide structure and material properties affect the adhesion and proliferation of model fibroblast and osteoblast cell lines.