UDE COBRE: PEPTIDE-BASED BIOMATERIALS WITH ENVIRON SENSITIVE MORPHOLOGIES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。项目二：施耐德和波尚水凝胶，一类生物技术不可或缺的材料，如组织工程和微流体，通常由高分子量聚合物制成。用于组织工程的理想水凝胶支架是易于使用无毒化学物质合成的，具有生物相容性，促进细胞粘附/增殖并且可生物降解。在材料特性方面，它们的形态应该是多孔的，便于细胞运动和营养物质/废物的扩散。然而，尽管它们具有多孔性，但这些材料必须具有机械刚性。我们开发了一种替代策略，利用自组装肽来制备反应性水凝胶。从多肽制备材料是有利的，因为多肽是快速合成的，新的氨基酸残基很容易纳入定制的功能。此外，由于我们的水凝胶是由纯自组装机制制备的，因此不需要外源性毒性交联剂。该策略采用了经过设计的肽，这些肽在分子内折叠成b发夹构象，便于自组装。该系统的关键是肽必须在分子内折叠才能发生自组装导致水化。通过设计仅在所需的环境线索存在时折叠的肽，可以构建响应材料。发夹被设计成根据pH值和离子强度的变化、光线和温度的变化而折叠。水凝胶在微观和纳米尺度上多孔且水化良好，但具有刚性（G′=1600Pa），剪切薄，剪切停止后自愈。重要的是，这些水凝胶支持NIH 3T3成纤维细胞（小鼠）的附着和增殖，表明它们可能用作组织工程支架。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project II: Schneider and Pochan Hydrogels, a class of materials integral to biotechnologies such as tissue engineering and microfluidics are classically made from high molecular weight polymers. Ideal hydrogel scaffolds for use in tissue engineering are easily synthesized using non-toxic chemistries, biocompatible, promote cell adhesion/proliferation and are biodegradable. In terms of material properties, their morphology should be porous for cell motility and nutrient/waste diffusion. However, despite their porous nature, these materials must be mechanically rigid. We developed an alternate strategy that employs self-assembling peptides to prepare responsive hydrogels. Preparing materials from peptides is advantageous since peptides are quickly synthesized and novel amino acid residues readily incorporated for tailored functions. Also, since our hydrogels are prepared from a pure self-assembly mechanism, there is no need for exogenous toxic cross linking agents. The strategy employs designed peptides that intramolecularly fold on cue into a b-hairpin conformation that is amenable to self-assembly. Key to this system is that the peptide must be intramolecularly folded before self-assembly leading to hydrogelation can occur. By designing peptides that only fold when desired environmental cues are present, responsive materials may be constructed. Hairpins have been designed to fold in response to pH and ionic strength changes, light, and temperature changes. Hydrogels are porous and well hydrated on the micro- and nano-scale, but are rigid (G'=1600Pa), shear thin and self heals after cessation of shear. Importantly, these hydrogels support the attachment and proliferation of NIH 3T3 fibroblasts (mouse), indicating their possible use as tissue engineering scaffolds.