INTELLECTUAL MERIT: This proposal describes an integrated research and educational plan based on the PI's expertise in biomaterials design for tissue engineering and together will provide unique and exciting opportunities for promoting diversity in STEM disciplines at the University of Colorado. The theme of the PI's overall research plan is to design innovative and intelligent hydrogels for applications in tissue engineering, which mimic nature's unique way of guiding complex tissue development and maintaining homeostasis. The proposed research builds upon recent developments in stem cell research, which suggest that stem cell interactions with the extracellular matrix (ECM) provide both biochemical and biomechanical cues to guide differentiation. Towards this end, the PI will build a fundamental connection between the hydrogel environment (via its chemistry and structure) and the translation of mechanical forces (in the form of dynamic compressive strains) through the hydrogel to the cells to guide stem cell differentiation in 3D. This fundamental knowledge will be used to develop innovative multi-structured hydrogels where the structure and chemistry are spatially controlled to regulate both biochemical and biomechanical cues in 3D and differentially guide stem cell differentiation into cartilage and bone in a single hydrogel for osteochondral tissue engineering. The 3D hydrogel stem cell niches developed by this work will enable certain biochemical (the ECM) and biomechanical cues to be isolated and their roles elucidated in MSC differentiation. By systematically controlling the hydrogel niche the PI will be able to elucidate fundamental mechanisms involved in mesenchymal stem cell (MSC) differentiation that involve their ECM and biomechanical environment. From this fundamental knowledge this research will build innovative and complex 3D hydrogels for tissue engineering which (1) recapitulate these cues in 3D to mimic, to a certain degree, the translation of biomechanical signals within a normal joint and (2) are designed to manipulate stem cell fate to drive MSCs down differentiated lineages within a single hydrogel. The proposed work will develop a new class of scaffolds for regenerating osteochondral tissues. Overall, this research will impact that the training of 4 graduate students and at least 15 undergraduates
BROADER IMPACTS: The proposed educational activities are closely intertwined with the PI?s overall research theme, which together will build a strong and diverse research program. The PI will work closely with Adams State College, a Hispanic Serving Institution, in rural Colorado to develop a nurturing path for students, particularly those who are from Hispanic or Latino origin, from low-income families and/or first generation college students, to pursue engineering careers. The proposed plan is rooted in creating strategies to increase participation in the pre-engineering program at Adams State College (ASC) by closely integrating the PI?s research in tissue engineering with educational programs. Through close collaboration with ASC, the PI will create opportunities for ASC students to explore the University of Colorado at Boulder (CU) campus and enhance their academic skills through a 10-week summer research program at CU-Boulder. Together, these objectives will prepare ASC students to transfer successfully to CU-Boulder into Engineering and obtain a B.S. degree in Engineering. The proposed educational activities will begin a life-long partnership with a rural Colorado college, ASC, and create a pilot summer program that ultimately can be expanded to broadly impact other rural colleges.
