Rational Design of Novel Collagen-Based Biomaterials

该奖项由加州大学欧文分校材料研究部的生物材料计划颁发，旨在利用研究人员为该项目开发的重组酵母系统，利用一种新颖的“自下而上”策略来合成类胶原聚合物及其模拟物。这一方法有望在可纳入工程生物聚合物的一系列独立的生物和材料特性方面提供前所未有的灵活性。创造能够指导细胞活动的新的人工支架的能力是促进许多领域的关键组成部分，如再生医学、疾病治疗和机械细胞研究。由于胶原蛋白是细胞外基质中含量最丰富的蛋白质，而且它与细胞动态相互作用，因此基于胶原蛋白的聚合物可能会模仿自然特征，这些特征比纯合成系统更好。作为该项目的一部分，研究人员将引入非天然半胱氨酸交联点和基质金属蛋白酶蛋白水解域，并将研究它们对胶原结构、机械性能、分子运输特性和基于细胞的反应的影响。该项目将成为培养理工科本科生和研究生的理想平台。参与这一跨学科合作的学生将获得对传统不同领域之间重要协同作用的综合视角。创造能够模拟生物基质并表现出广泛新特性的新材料的能力在推动与健康相关的研究(如再生医学和疾病疗法)方面尤为关键。胶原蛋白是一种丰富的天然蛋白质，可以与周围的细胞动态地相互作用。通过制造天然胶原蛋白的模拟物，研究人员将检查新的机械、结构和生物响应生物材料的范围和适用性。这可以使人们更好地理解这种材料如何用于疾病治疗。该项目将成为培养理工科本科生和研究生的理想平台。由于这种合作的跨学科性质，参与这项研究的学生将获得一个综合的视角，了解传统不同领域之间的重要协同作用，这些领域现在是最先进的研究所需的。除了对学生的实践培训外，这项拟议工作的成果也将纳入研究生课程。

This award by the Biomaterials program in the Division of Materials Research to University of California-Irvine is to synthesize collagen-like polymers and their mimics utilizing a novel "bottom-up" strategy using recombinant yeast system that was developed by the investigators for this project. This approach is expected to allow unprecedented flexibility in the range of independent biological and material properties that can be incorporated in the engineered biopolymers. The ability to create new artificial scaffolds that can direct the activity of cells is a critical component of furthering a number of areas such as regenerative medicine, therapies for disease, and mechanistic cell studies. Since collagen is the most abundant protein in the extracellular matrix and it dynamically interacts with cells, a collagen-based polymer could potentially mimic natural characteristics that are better than purely synthetic systems. As part of this project, investigators will introduce non-native cysteine cross-linking sites and matrix metalloproteinase proteolytic domains, and will examine their effects on collagen architecture, mechanical properties, molecular transport characteristics, and cell-based responses. The project will serve as an ideal platform to train both undergraduate and graduate students in science and engineering. Students participating in this interdisciplinary collaboration will gain an integrated perspective of the important synergies between traditionally diverse fields.The capability to create novel materials which can mimic biological matrices and exhibit a broad range of new properties is especially critical in advancing health-related research such as regenerative medicine and therapies for disease. Collagen is an abundant, natural protein which dynamically interacts with its surrounding cells. By fabricating mimics of natural collagen, the investigators will examine the scope and applicability of new mechanical, structural, and biologically-responsive biomaterials. This can lead to a better understanding of how such materials can be used in disease treatment. The project will serve as an ideal platform to train both undergraduate and graduate students in science and engineering. Due to the interdisciplinary nature of this collaboration, students participating in this research will gain an integrated perspective of the important synergies among traditionally diverse fields that are now needed for a state-of-the-art research. In addition to hands-on training for students, the results from this proposed work will also be incorporated into graduate courses.