CAREER: Multifunctional Dynamic Surfaces for Engineering Cell Microenvironments

ID：MPS/DMR/BMAT（7623）1151529 PI：Shen，Wei ORG：University of Minnesota Title： 职业：多功能动态表面工程细胞微环境智力优势：使用合成材料工程化人工细胞微环境，概括其体内对应物的基本特征，以指导干细胞命运选择已成为再生医学的重要策略。 然而，它仍然是一个挑战，创造材料，模拟不溶性配体的动态呈现，限制了控制和研究干细胞的命运选择在明确的仿生细胞微环境的能力。 该项目的目标是开发一种方法来工程动态生物材料，使可逆和正交调节的多个不溶性配体的细胞表面受体，而不暴露细胞的配体的可溶性对应物，并使用这样的工程材料来研究中胚层分化的人诱导多能干细胞（iPSC）在细胞微环境中呈现动态控制的整合素配体作为模型系统。 这项建议的具体目标是：（1）能够可逆和正交地呈递多个不溶性配体的底物的设计、制备和物理-化学表征，（2）研究不溶性配体的细胞可接近和细胞不可接近状态的可逆和正交调节，（3）研究人iPSC响应于两种特异性整合素的动态调节的配体向心肌和血液内皮祖细胞的中胚层分化。 该项目的完成将弥合理解和控制干细胞命运选择响应动态调节的不溶性配体和缺乏使能动态生物材料之间的差距。 基于这种方法的多功能动态生物材料将允许创建更好地模拟其体内对应物的细胞微环境。 这些仿生人工细胞微环境不仅可以引导干细胞更有效地分化为细胞治疗所需的谱系，还可以在良好控制的系统中研究发育生物学的基础知识，这在动物研究中是很难实现的。本研究所开发的方法可用于动态调控许多不溶性配体，构建各种仿生细胞微环境 研究和控制这些工程系统中的细胞行为、命运选择和功能将对技术发展和基本理解产生影响。 拟议的教育活动旨在培养生物材料和组织工程领域的合格和多样化的劳动力，将与PI的研究兴趣完全结合起来。 PI将提供智能生物材料的实践演示（葡萄糖敏感凝胶，工程细胞片的温度响应材料，允许细胞封装的水凝胶），智能生物材料研讨会，以及明尼阿波利斯公立学校高科技女孩协会和探索工程和物理科学课程职业的学生的夏季研究机会。 她将通过参与North星星STEM计划来促进代表性不足的少数民族和女性本科生的研究活动，她将帮助在明尼苏达大学的生物医学工程课程中建立一个强大的生物材料和组织工程轨道。

ID: MPS/DMR/BMAT(7623) 1151529 PI: Shen, Wei ORG: University of MinnesotaTitle: CAREER: Multifunctional Dynamic Surfaces for Engineering Cell MicroenvironmentsINTELLECTUAL MERIT: Using synthetic materials to engineer artificial cell microenvironments that recapitulate the essential characteristics of their in vivo counterparts to guide stem cell fate selection has become an important strategy in regenerative medicine. However, it remains a challenge to create materials that mimic dynamic presentation of insoluble ligands, limiting the ability to control and study stem cell fate selection in well-defined biomimetic cell microenvironments. The goal of the project is to develop a method to engineer dynamic biomaterials that enable reversible and orthogonal regulation of multiple insoluble ligands to cell surface receptors without exposing cells to the soluble counterparts of the ligands and to use such engineered materials to study mesodermal differentiation of human induced pluripotent stem cells (iPSCs) in cell microenvironments presenting dynamically controlled integrin ligands as a model system. The specific objectives of this proposal are: (1) design, preparation, and physical-chemical characterization of substrates capable of presenting multiple insoluble ligands reversibly and orthogonally, (2) investigation of reversible and orthogonal regulation of cell-accessible and cell-inaccessible states of the insoluble ligands, (3) investigation of mesodermal differentiation of human iPSCs toward myocardial and hemato-endothelial progenitors in response to dynamically modulated ligands for two specific integrins. Completion of this project will bridge the gap between the need for understanding and controlling stem cell fate selection in response to dynamically modulated insoluble ligands and the lack of enabling dynamic biomaterials. Multifunctional dynamic biomaterials based on this method will allow creation of cell microenvironments that better emulate their in vivo counterparts. These biomimetic artificial cell microenvironments will not only guide more efficient stem cell differentiation toward desired lineages for cell-based therapy, but also enable the study of fundamentals of developmental biology in well-controlled systems, which is difficult to access with animal studies.BROADER IMPACTS: The approach developed in this project can be adapted for dynamic modulation of many insoluble ligands of interest to construct a variety of biomimetic cell microenvironments. Study and control of cell behavior, fate selection, and functions in these engineered systems will have implications for both technological development and fundamental understandings. The proposed education activities, aimed at creation of a qualified and diversified workforce in the biomaterials and tissue engineering fields, will be completely integrated with the PI's research interests. The PI will give hands-on demonstrations of smart biomaterials (glucose-sensitive gels, temperature-responsive materials for engineering cell sheets, hydrogels allowing cell encapsulation), a seminar on smart biomaterials, and summer research opportunities to the students in the Minneapolis Public Schools High Tech Girls Society and the Exploring Careers in Engineering and Physical Science programs. She will promote the research activities of underrepresented minority and women undergraduate students through participation in the North Star STEM program, and she will help to establish a strong Biomaterials and Tissue Engineering track in the Biomedical Engineering curriculum at the University of Minnesota.