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：科罗拉多州标题：职业：多结构水凝胶控制MSC的生化和生物力学线索：促进多样性的综合计划智力优势：该提案描述了基于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，并将为促进科罗拉多大学STEM学科的多样性提供独特和令人兴奋的机会。 PI整体研究计划的主题是设计创新和智能水凝胶，用于组织工程，模仿自然界引导复杂组织发育和维持体内平衡的独特方式。 拟议的研究建立在干细胞研究的最新进展基础上，这表明干细胞与细胞外基质（ECM）的相互作用提供了生物化学和生物力学线索来指导分化。 为此，PI将在水凝胶环境（通过其化学和结构）与通过水凝胶到细胞的机械力（以动态压缩应变的形式）的转化之间建立基本联系，以引导干细胞在3D中分化。 这些基础知识将用于开发创新的多结构水凝胶，其中结构和化学在空间上受到控制，以调节3D中的生化和生物力学线索，并在单一水凝胶中差异化地引导干细胞分化为软骨和骨，用于骨软骨组织工程。 这项工作开发的3D水凝胶干细胞龛将使某些生化（ECM）和生物力学线索被分离，并阐明它们在MSC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，包括其ECM和生物力学环境。 从这一基础知识，这项研究将建立创新和复杂的3D水凝胶组织工程，（1）概括这些线索在3D模拟，在一定程度上，生物力学信号在正常关节内的翻译和（2）被设计为操纵干细胞的命运，以驱动MSC分化的谱系在一个单一的水凝胶。 拟议的工作将开发一类用于再生骨软骨组织的新型支架。 总的来说，这项研究将影响4个研究生和至少15个本科生的培训更广泛的影响：拟议的教育活动是密切交织在一起的PI？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将与科罗拉多农村的西班牙裔服务机构亚当斯州立学院密切合作，为学生，特别是那些来自西班牙裔或拉丁裔，来自低收入家庭和/或第一代大学生的学生，制定一条培养道路，以追求工程事业。 拟议的计划是植根于创造战略，以增加参与工程前计划在亚当斯州立学院（ASC）的密切结合PI？组织工程学的研究与教育计划。 通过与ASC的密切合作，PI将为ASC学生创造机会，探索科罗拉多大学博尔德分校（CU）的校园，并通过在CU-Boulder为期10周的夏季研究计划提高他们的学术技能。 总之，这些目标将准备ASC学生成功转移到CU博尔德进入工程，并获得学士学位。 工程学学位。 拟议中的教育活动将开始与科罗拉多农村大学ASC建立终身伙伴关系，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大学。

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.