Synthesis of Peptide-based Zwitterionic Cross-linkers and Evaluation in Bioadaptable Hydrogels

非技术摘要：由称为单体的重复单元组成的聚合物无处不在。含有大量水的聚合物，如隐形眼镜，被称为水凝胶。水凝胶的一种用途是将这些材料放入体内，以帮助克服生物缺陷(损伤、疾病、损伤等)。人体对这些“生物材料”的反应取决于材料的性质--身体排斥不相容的材料。同样，物理特征应该与原始组织的物理特征相匹配。考虑到如此广泛的应用，需要对生物材料进行更多的控制。该项目的目标是创造一种新的水凝胶，提供更好的材料特性控制。这将通过创造新的带电但中性的氨基酸分子来实现，这些分子将水凝胶结合在一起(交联剂)。这些物种将与其他带电单体反应，形成三维水凝胶网络。将研究的重要水凝胶特性包括生物物种的结合、生物信号的传递、材料的物理性质以及生物材料随时间的分解。材料的性质将与氨基酸分子的组成联系在一起。其结果将是一个具有可控性能的新水凝胶库，可广泛使用。还将与当地高中教师一起为专业发展研讨会创建一系列实验，将这门科学带到课堂上。技术摘要：需要新的生物适应材料来应对与使用聚合物材料的生物医学疗法和其他生物应用相关的临床挑战。要被定义为生物适应性，材料必须满足四个标准：抗非特定蛋白质吸附、传递特定生物信号分子(蛋白质、多肽等)的能力、可调节的机械性能和可调节的降解行为。聚两性生物材料因其无污染行为、传递生物活性蛋白的能力、多种控制其机械性能的方法以及可调的降解行为而被定义为生物适应性材料。然而，这些聚合物的进步的一个重要限制是缺乏两性离子交联剂分子，以及随后对指导其最终使用的交联剂结构和物理性质关系的了解。总体目标是设计和合成一个基于多肽的两性离子交联剂的文库，这些交联剂将被加入到聚两性离子水凝胶中，以发展交联剂物种和所得到的聚合物水凝胶之间的结构-性质关系。这将导致对交联剂设计标准的基本理解，这反过来将促进生物适应性生物材料水凝胶的开发。假设分子水平上对长度、化学、电荷间距、电荷密度和侧链呈现的控制将导致生物适应性聚两性水凝胶的展示。这一假设将通过合成具有可控结构的基于多肽的交联剂并将这些交联剂加入到聚两性水凝胶中来检验。将对水凝胶性能指标进行评估，从而使聚两性聚合物水凝胶性能指标的结构-性能关系与多肽两性离子交联剂库中的结构设计特征基本相关。该奖项将为爱达荷大学的学生提供基于课程的本科生研究经验(CURE)。该团队还将提供教师研讨会，以拓宽水凝胶主题的知识。该项目由生物材料(BMAT)计划和既定的刺激竞争研究计划(EPSCoR)联合资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Non-Technical Abstract:Polymers, which are composed of repeating units called monomers, are everywhere. Polymers that contain large amounts of water, like contact lenses, are called hydrogels. One use of hydrogels involves placing these materials into the body to help overcome a biological deficiency (injury, disease, impairment, etc.). The body’s response to these “biomaterials” is dependent upon the material properties - incompatible materials are rejected by the body. Similarly, the physical characteristics should match those of the original tissue. There is a need for more control over the biomaterials given this broad range of applications. The goal of this project is to create a new class of hydrogels that provide improved control of the material properties. This will be done through the creation of new charged, but neutral, amino acid-based molecules that hold the hydrogel together (cross-linkers). These species will react with other charged monomers creating three-dimensional hydrogel networks. Important hydrogel properties that will be investigated include the binding of biological species, the delivery of biological signals, the material physical properties, and the breakdown of the biomaterial over time. The material properties will be linked to the composition of the amino acid-based molecules. The result will be a library of new hydrogels with controlled properties for broad use. A series of experiments will also be created for professional development workshops with local high school teachers to bring this science to the classroom.Technical Abstract:There is a need for novel bioadaptable materials to address clinical challenges associated with biomedical therapies and other biological applications that use polymer-based materials. To be defined as bioadaptable, the material must meet four criteria: resistance to nonspecific protein adsorption, the ability to deliver specific biological signaling molecules (proteins, peptides, etc.), tunable mechanical properties, and tunable degradation behavior. Polyampholyte biomaterials show promise for being defined as bioadaptable because of their demonstrated nonfouling behavior, ability to deliver bioactive proteins, multiple approaches for controlling their mechanical properties, and tunable degradation behavior. However, a significant limitation to the advancement of these polymers is the lack of zwitterionic cross-linker molecules and a subsequent understanding of the cross-linker structure and physical property relationships that will guide their end use. The overall goal is to design and synthesize a library of peptide-based zwitterionic cross-linkers which will be incorporated into polyampholyte hydrogels to develop structure-property relationships between the cross-linker species and the resulting polymer hydrogels. This will lead to a fundamental understanding of design criteria for the cross-linker which in turn will facilitate development of bioadaptable biomaterial hydrogels. It is hypothesized that molecular-level control over the length, chemistry, charge spacing, charge density, and pendant side chain presentation will lead to the demonstration of bioadaptable polyampholyte hydrogels. This hypothesis will be tested by synthesizing peptide-based cross-linkers with controlled structure and incorporating these cross-linkers into polyampholyte hydrogels. Hydrogel performance metrics will be evaluated, resulting in a fundamental correlation of the structure-property relationships of polyampholyte hydrogel performance metrics to structural design features in the library of peptide-based zwitterionic cross-linkers. The award will provide course-based undergraduate research experiences (CUREs) for students at the University of Idaho. The team will also provide teacher workshops to broaden knowledge in the topic of hydrogels.This project is jointed funded by the Biomaterials (BMAT) program and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.