CAREER: Multi-Structured Hydrogels to Control Biochemical and Biomechanical Cues to MSCs: An Integrative Plan to Promote Diversity

ID: MPS/DMR/BMAT(7623) 0847390 PI: Bryant， Stephanie ORG: ColoradoTitle：职业：多结构水凝胶来控制MSCs的生化和生物力学线索：促进多样性的综合计划该提案描述了一个基于PI在组织工程生物材料设计方面的专业知识的综合研究和教育计划，将为促进科罗拉多大学STEM学科的多样性提供独特而令人兴奋的机会。PI整体研究计划的主题是设计创新的智能水凝胶，用于组织工程，模仿自然引导复杂组织发育和维持体内平衡的独特方式。该研究基于干细胞研究的最新进展，该研究表明干细胞与细胞外基质（ECM）的相互作用为指导分化提供了生化和生物力学线索。为此，PI将在水凝胶环境（通过其化学和结构）和机械力（以动态压缩应变的形式）通过水凝胶传递到细胞之间建立基本联系，以指导干细胞在3D中分化。这些基础知识将用于开发创新的多结构水凝胶，其中结构和化学成分在空间上受到控制，以调节3D的生化和生物力学线索，并在骨软骨组织工程的单个水凝胶中差异引导干细胞分化为软骨和骨。这项工作开发的3D水凝胶干细胞壁龛将使某些生化（ECM）和生物力学线索得以分离，并阐明它们在间质干细胞分化中的作用。通过系统地控制水凝胶生态位，PI将能够阐明涉及间充质干细胞（MSC）分化的基本机制，包括它们的ECM和生物力学环境。基于这些基础知识，本研究将为组织工程构建创新和复杂的3D水凝胶(1)以3D形式再现这些线索，在一定程度上模仿正常关节内生物力学信号的翻译；(2)设计用于操纵干细胞命运，以驱动MSCs在单个水凝胶内分化谱系。本研究将开发一种用于骨软骨组织再生的新型支架。总体而言，这项研究将影响4名研究生和至少15名本科生的培训。更广泛的影响：拟议的教育活动与PI密切相关？的整体研究主题，这将共同建立一个强大的和多样化的研究计划。PI将与科罗拉多州农村地区的西班牙裔服务机构亚当斯州立学院（Adams State College）密切合作，为学生，特别是来自西班牙裔或拉丁裔、低收入家庭和/或第一代大学生，开辟一条从事工程职业的培养途径。拟议的计划植根于制定战略，通过密切整合PI？组织工程与教育项目的研究。通过与ASC的密切合作，PI将为ASC的学生创造机会，探索科罗拉多大学博尔德分校（CU）校园，并通过在科罗拉多大学博尔德分校为期10周的暑期研究项目提高他们的学术技能。总之，这些目标将准备ASC学生成功地转到科罗拉多大学博尔德分校进入工程专业，并获得工程学士学位。拟议的教育活动将与科罗拉多州一所农村学院ASC建立终身合作伙伴关系，并创建一个试点暑期项目，最终可以扩大到广泛影响其他农村学院。

ID: MPS/DMR/BMAT(7623) 0847390 PI: Bryant, Stephanie ORG: ColoradoTitle: CAREER: Multi-structured Hydrogels to Control Biochemical and Biomechanical Cues to MSCs: An Integrative Plan to Promote DiversityINTELLECTUAL 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 undergraduatesBROADER 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.