UDE COBRE: PEPTIDE-BASED BIOMATERIALS WITH ENVIRON SENSITIVE MORPHOLOGIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 项目II：施耐德和波昌 水凝胶是组织工程和微流体等生物技术不可或缺的一类材料，传统上是由高分子量聚合物制成的。用于组织工程的理想水凝胶支架很容易用无毒的化学方法合成，具有生物相容性，促进细胞黏附/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，以利于细胞运动和营养/废物的扩散。然而，尽管这些材料具有渗透性，但它们必须是机械刚性的。我们开发了一种替代策略，使用自组装肽来制备响应性水凝胶。从多肽制备材料是有利的，因为多肽可以快速合成，并且新的氨基酸残基很容易被结合以实现定制的功能。此外，由于我们的水凝胶是通过纯自组装机制制备的，因此不需要外源有毒交联剂。该策略利用设计的多肽，根据提示在分子内折叠成易于自我组装的b-发夹构象。这个系统的关键是，在自组装导致水凝胶发生之前，多肽必须在分子内折叠。通过设计只有在存在所需的环境线索时才折叠的多肽，可以构建出响应材料。发夹被设计成可以随着pH和离子强度的变化、光和温度的变化而折叠。水凝胶在微米和纳米尺度上是多孔的，水化良好，但具有刚性(G‘=1600Pa)，剪切变薄，停止剪切后会自我愈合。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.