CAREER: Integrating Biomaterials and Biology for Control of Cell Function in 3D Matrices

ID：MPS/DMR/BMAT(7623)0847253 PI：Kong，Hyunjoon ORG：Illinois-UCTitle：Career：生物材料和生物学用于控制3D材料中的细胞功能该奖项由2009年美国复苏和再投资法案(公共法律第111-5号)资助。人工构建的ECM模拟生物材料通常与细胞和生长因子结合在一起，用于组织缺损和几种慢性病的生物学研究和临床治疗。然而，由于对复杂的细胞微环境的了解有限，生长因子所发挥的生物学作用尚不清楚。这种认识的缺乏也限制了生长因子的治疗效果。为了更深入地了解生长因子在调节细胞功能中的作用，提出的研究目标是创造一种细胞囊化水凝胶，使研究人员能够通过设计细胞微环境来调节生长因子诱导的细胞内信号转导。PI特别假设水凝胶硬度调节生长因子与细胞结合的程度，从而影响生长因子刺激细胞生长和分化的效果。验证这一假设的实验将需要通过构建链密度几乎恒定但交联度不同的水凝胶来分离目前相互依赖的凝胶硬度和对营养物质的渗透性。预计在给定链密度下，交联剂密度的变化不会对凝胶中的扩散产生实质性影响。BROADER的影响：成功证明基质弹性和生长因子功效可以脱钩，将为组织工程和再生医学的进步开辟道路。拟议的教育目标是为大学生创建一个跨学科的生物材料课程，以及旨在填补知识缺口的各种外展项目，这些项目旨在为有积极性和多样化的科学家填补知识缺口。该教育计划将利用现有的面向大学预科学生(包括女性和少数族裔)和科学教师的机构外展计划，以确保成功完成学业。这个职业计划的目标将通过实施四个研究和教育项目来实现：(项目1)设计和创造一种生物材料，使生物材料硬度和营养运输之间的相互依赖脱钩；(项目2)建立一套描述生长因子诱导的信号转导与生物材料硬度的综合生物材料设计原则；(项目3)创建一门跨学科课程，题为？生物材料-生物系统相互作用在生物和医学？并为学生提供研究机会，作为其他机构可以采用、适应和建立的典范；以及(项目4)向大学预科学生和教师介绍生物材料和生物学之间的科学，以激励他们，增加生物材料领域的学生数量和多样性。

ID: MPS/DMR/BMAT(7623) 0847253 PI: Kong, Hyunjoon ORG: Illinois-UCTitle: CAREER: Biomaterials and Biology for Control of Cell Function in 3D MatricesThis award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).INTELLECTUAL MERIT: The extracellular matrix (ECM) in human tissues plays a critical role in protecting and nourishing cells by providing cell adhesion sites and sequestering growth factors. Artificially constructed ECM-simulating biomaterials are often combined with cells and growth factors for use in biological studies and clinical treatments of tissue defects and several chronic diseases. However, the biological role played by growth factors remains unclear due to limited understanding about complex cellular microenvironment. This lack of understanding also limits the therapeutic efficacy of growth factors. In order to establish a more thorough understanding of the role of growth factors in regulating cell function, the proposed research goal is to create a cell-encapsulating hydrogel that allows researchers to regulate growth factor-induced signal transduction in cells by engineering the cellular microenvironment. The PI specifically hypothesizes that the hydrogel stiffness modulates the extent of growth factor binding to cells and subsequently affects the efficacy of the growth factors in stimulating cell growth and differentiation. Experiments to examine this hypothesis will require decoupling the currently interdependent gel stiffness and permeability to nutrients by building hydrogels with nearly constant chain density but with varying crosslink density. It is expected that changes in crosslink density will not materially affect diffusion through the gel at a given chain density.BROADER IMPACTS: A successful demonstration that matrix elasticity and growth factor efficacy can be decoupled would open the way to advances in tissue engineering and regenerative medicine. The proposed educational goal is to create a cross-disciplinary biomaterials curriculum for college students plus a variety of outreach programs designed to fill the knowledge gap with motivated and diverse scientists. The educational plan will leverage existing institutional outreach programs for pre-college students, including women and minorities, and science teachers to ensure successful completion. The goals of this CAREER proposal will be accomplished by implementing four research and educational projects: (Project 1) designing and creating a biomaterial that decouples the interdependency between biomaterial stiffness and nutrient transport; (Project 2) establishing a set of integrative biomaterial design principles that describe growth factor-induced signal transduction with biomaterial stiffness; (Project 3) creating a cross-disciplinary course entitled ?Biomaterial-Biological Systems Interactions in Biology and Medicine? and providing students with research opportunities to serve as a model that other institutions may adopt, adapt, and build upon; and (Project 4) introducing pre-college students and teachers to the science between biomaterials and biology to inspire them and increase the number and diversity of students in the biomaterial field.