CAREER: Multifunctional Dynamic Surfaces for Engineering Cell Microenvironments

ID：MPS/DMR/BMAT(7623)1151529 PI：沈，魏ORG：明尼苏达大学标题：Career：用于工程细胞微环境的多功能动态表面INTELLECTUCT优点：使用合成材料来设计人工细胞微环境，概括其体内同行的基本特征，以指导干细胞命运选择已成为再生医学中的一项重要策略。然而，创造模拟不溶性配体动态呈现的材料仍然是一个挑战，限制了在明确定义的仿生细胞微环境中控制和研究干细胞命运选择的能力。该项目的目标是开发一种能够在不使细胞暴露于可溶配体的情况下对细胞表面受体进行可逆和正交调节的动态生物材料，并将这种工程材料用于研究人诱导多能干细胞(IPSCs)在呈现动态控制的整合素配体的细胞微环境中的中胚层分化。这项建议的具体目标是：(1)设计、制备和物理化学表征能够可逆和正交地呈现多个不溶性配体的底物；(2)研究不可溶配体的细胞可及状态和细胞不可及状态的可逆和正交调节；(3)研究两种特定整合素的动态调节配体对人IPSCs向心肌和血液内皮祖细胞的中胚层分化的响应。该项目的完成将弥合需要了解和控制干细胞命运选择以响应动态调节的不溶性配体与缺乏使能的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造更好地模仿体内同行的细胞微环境。这些仿生人工细胞微环境不仅将引导干细胞更有效地分化为基于细胞的治疗所需的谱系，而且还可以在受控良好的系统中研究发育生物学的基本原理，这是动物研究难以达到的。BROADER影响：本项目开发的方法可以适用于动态调节许多感兴趣的不溶性配体，以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都有意义。拟议的教育活动旨在生物材料和组织工程领域培养一支合格和多样化的劳动力队伍，将完全与PI的研究兴趣相结合。PI将向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项目的学生提供智能生物材料(葡萄糖敏感凝胶、工程细胞膜的温度响应材料、允许细胞封装的水凝胶)的动手演示、智能生物材料研讨会和暑期研究机会。她将通过参加北极星STEM计划，促进未被充分代表的少数族裔和女性本科生的研究活动，并将帮助在明尼苏达大学的生物医学工程课程中建立强大的生物材料和组织工程课程。

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.