Hydrogels from Designed Peptides

描述（由申请人提供）：通过肽自组装制备水凝胶允许通过设计单个组成分子来定义最终的生物材料性质。化学功能性、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设计。在本文中，肽被设计成响应于外部刺激而分子内折叠成能够自组装的β-发夹构象。折叠的发夹结构组装成稀的但坚硬的水凝胶，在纳米到微米尺度上显示出多孔性.触发折叠允许材料形成的时间和空间控制。甘精胰岛素将由各种生理相关刺激触发;例如pH、盐、钙离子、温度和光。化学上良性的折叠/自组装策略，以及所得水凝胶的固有肽性质，为成纤维细胞和成骨细胞提供了潜在的组织工程基质。肽的设计原则，导致刚性，多孔水凝胶能够支持细胞粘附和增殖将确定直接观察肽结构如何影响自组装过程，材料形态，材料性能和细胞相容性。跨学科的“分子到材料”的设计和拟议的水凝胶化系统的性能表征将通过化学/生物化学和材料科学与工程部门之间的密切合作来完成。这项研究工作将：1。获得导致水凝胶形成的折叠和自组装过程以及分子设计如何影响材料特性的基本理解。2.通过设计活性分子内折叠触发器，使肽溶液能够适时进行水凝胶化，增强发夹型水凝胶的可加工性。 3.确定肽结构和材料特性如何影响模型成纤维细胞和成骨细胞系的粘附和增殖。

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.