Catch and Release: Biomolecular Ligation and Cleavage Strategies for Generating Instructive and Dynamically Responsive 3D Biomaterials

这一奖项由伊利诺伊大学香槟分校材料研究部的生物材料计划颁发，旨在创建一个基于胶原-糖胺多聚糖生物材料、二苯甲酮光固定化和刺激响应释放化学的强大系统，使其能够在空间和时间上控制广泛的粘连和增殖线索(生长因子、配体、蛋白质、碳水化合物、基因序列等)的呈现。这里使用的系统方法将胶原生物材料与光化学控制的固定化技术相结合，将能够设计出适用于复杂组织工程应用的新型生物材料，概括了天然组织和组织界面中发现的大部分生物分子复杂性。简单而通用的系链化学允许广泛的生物分子的空间定位以及相同生物分子的外源性或内源性线索释放，对于产生新型的指导性生物材料将是无价的。这种材料将提供模拟自然细胞外基质的动态和空间异质性的能力。除了开发在3D生物材料中创建空间和时间模式的指导线索的分子通用方法的基本见解外，这项工作还将使新型生物材料的制造成为可能，既用于转化再生医学，也用于细胞行为的机械研究。这项工作的更广泛影响既是重新想象如何使用生物材料来控制细胞行为，也是为了提供宝贵的多学科培训经验，为来自校园内多个系和学院的本科生提供重要的研究项目。通过这样做，这个项目将创造一个高度跨学科的环境，暴露、教育和授权下一代本科生和研究生工程师和化学家，以应对生物、物理和工程科学交叉领域的关键挑战。组织是复杂的三维环境，呈现多种类型的线索，调节细胞的命运。目前还不存在在三维生物材料内空间控制生物分子显示的能力，但这是一个基本的技术差距，必须弥合，以开发下一代生物材料，用于体内、组织再生和体外，以研究细胞如何感知和响应其微环境。使用这里开发的图案化工具创建的材料将对周围的细胞和组织具有启发性和响应性，并将提供对细胞-基质相互作用的机械洞察，以及用于更复杂的再生医学应用的先进生物活性材料。通过一个协调的研究和教育计划，该项目将直接支持校园内的一些关键外展计划。在这个项目中开发的工具将作为正在进行的和未来在化学-生物-工程学科的交汇处为科学和工程专业的未被充分代表的本科生进行的新型研究项目的基础，并将形成正在进行的校园组织工程课程中的新的教学模块的基础。

This award by the Biomaterials program in the Division of Materials Research to University of Illinois at Urbana-Champaign is to create a robust system based on collagen-glycosaminoglycan biomaterials, benzophenone photoimmobilization, and stimuli-responsive release chemistries that enables both spatial and temporal control over the presentation of a wide range of adhesive and proliferative cues (growth factors, ligands, proteins, carbohydrates, genetic sequences, etc.). The systematic approach used here to integrate collagen biomaterials with photochemically controlled immobilization techniques will enable design of new classes of biomaterials for complex tissue engineering applications that recapitulate much of the biomolecular complexity found in native tissues and tissue interfaces. Simple, yet generic tethering chemistries that allow spatial localization of a wide range of biomolecules as well as exogenously or endogenously cued release of the same biomolecules will be invaluable for generating novel classes of instructive biomaterials. Such materials would offer the ability to mimic the dynamic and spatial heterogeneities of the natural extracellular matrix. Apart from basic insights into developing molecularly general methods for creating spatially and temporally patterned instructive cues within 3D biomaterials, this work will enable fabrication of new classes of biomaterials for both translational regenerative medicine as well as mechanistic investigations of cell behavior. Broader impacts of this work are both to re-imagine how biomaterials can be used to control cell behaviors as well as to provide a valuable multidisciplinary training experience that affords significant research projects for undergraduates from multiple departments and colleges across campus. In doing this, this project will create a highly interdisciplinary environment that exposes, educates, and empowers the next generation of undergraduate and graduate engineers and chemists to address critical challenges at the intersection of biological, physical, and engineering sciences. Tissues are complex, three-dimensional environments that present multiple types of cues which regulate cell fate. The ability to spatially control the display of biomolecules within three-dimensional biomaterials does not currently exist, but this is a fundamental technological gap that must be bridged to develop next generation biomaterials for use both in the body, to regenerate tissues, and outside of the body, to study how cells sense and respond to their microenvironment. Materials created using the patterning tools developed here will be both instructive and responsive to surrounding cells and tissues, and will provide mechanistic insights into cell-matrix interactions as well advanced bioactive materials for more complex regenerative medicine applications. Through a coordinated research and educational plan, the project will directly support a number of critical outreach programs on campus. The tools developed during this project will serve as the foundation for ongoing and future novel research projects at the confluence of chemistry-biology-engineering disciplines for under-represented undergraduate students in science and engineering, and will form the basis for a new teaching module in an ongoing Tissue Engineering course on campus.