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

非技术摘要：聚合物是由称为单体的重复单元组成的，它无处不在。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）。身体对这些“生物材料”的反应取决于材料的性质——不相容的材料会被身体排斥。同样，物理特征也应与原始组织相匹配。鉴于生物材料的广泛应用，有必要对其进行更多的控制。该项目的目标是创造一种新型的水凝胶，这种水凝胶可以更好地控制材料的性能。这将通过产生新的带电但中性的氨基酸分子来实现，这些分子将水凝胶固定在一起（交联剂）。这些物质会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、材料的物理特性以及生物材料随时间的分解。材料的性质将与氨基酸基分子的组成有关。结果将是一个具有控制性能的新水凝胶库，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，将这门科学带入课堂。技术摘要：需要新型生物适应性材料来解决与生物医学治疗和其他使用聚合物基材料的生物应用相关的临床挑战。要被定义为具有生物适应性，材料必须满足四个标准：对非特异性蛋白质吸附的抗性，传递特定生物信号分子（蛋白质，肽等）的能力，可调节的机械性能和可调节的降解行为。聚两性聚合物生物材料具有良好的生物适应性，因为它们具有良好的无污染性能、传递生物活性蛋白的能力、多种控制机械性能的方法以及可调节的降解行为。然而，这些聚合物发展的一个重大限制是缺乏两性离子交联剂分子，以及对交联剂结构和物理性质关系的后续理解，这将指导它们的最终用途。总体目标是设计和合成一个基于多肽的两性离子交联剂库，这些交联剂将被纳入聚两性聚合物水凝胶中，以发展交联剂种类与所得聚合物水凝胶之间的结构-性能关系。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发展。据推测，分子水平上对长度、化学性质、电荷间距、电荷密度和垂坠侧链表现的控制将导致生物适应性聚两性聚合物水凝胶的展示。这一假设将通过合成具有可控结构的肽基交联剂并将这些交联剂结合到聚两性聚合物水凝胶中来验证。将对水凝胶性能指标进行评估，从而得出多肽基两性离子交联剂库中多两性聚合物水凝胶性能指标与结构设计特征的结构-性能关系的基本相关性。该奖项将为爱达荷大学的学生提供基于课程的本科研究经验（CUREs）。该团队还将提供教师讲习班，以扩大水凝胶主题的知识。该项目由生物材料（BMAT）计划和促进竞争性研究的既定计划（EPSCoR）联合资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.