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

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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.