Spatial Control of Cell Behavior via Interfacial Bioorthogonal Chemistry

通过界面生物正交化学空间控制细胞行为

• 批准号: 1506613
• 负责人: Xinqiao Jia
• 金额: $ 45万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1506613&HistoricalAwards=false
• 关键词: Spatial; Control; Cell; Behavior; via

Spatial Control of Stem Cell Behavior via Interfacial Bioorthogonal Chemistry (NSF DMR, Biomaterials Program # DMR-1506613)Non-technical: Tissue engineering holds promise for creating off-the-shelf, implantable tissues or organs for the betterment of human health. Successful engineering of functional tissues requires the environment in which the cells originally reside in vivo be recreated ex vivo. In this project, a biomimetic scaffold will be created by combining a gelatinous material exhibiting desired spatial gradients with synthetic fibers displaying biochemical signals in a repetitive fashion. The individual components and the integrated scaffold will be produced using a novel process that takes advantage of an ultrafast, highly efficient coupling reaction. Such a process permits the spatial control of scaffold properties without having to rely on external, potentially toxic triggers or templates, thereby enabling facile incorporation of the patient's cells in the scaffold in 3D. The cell-populated scaffold will be mechanically stimulated to enhance tissue growth. The ultimate goal is to create tissues with the correct organization and proper functions. This work will enable the production of sophisticated materials to improve the quality of life for patients suffering from various diseases, thus justifying the public support. The PIs outreach and education efforts will help maintain the United States' global competitiveness. In addition to course development, student training, effort will be dedicated to the engaging and empowering of pre-service, early childhood teachers who will inspire the next generation scientists.Technical: This award to the University of Delaware (UD) aims to develop synthetic matrices with anisotropic features and spatial gradients to control the behavior of 3D encapsulated mesenchymal stem cells (MSCs) for the engineering of mechanically active soft tissues. The PIs will accomplish this goal by integrating a hyaluronic acid (HA)-based hydrogel with synthetic fibers produced de novo using designed monomers. The HA hydrogel will exhibit spatial variations of matrix stiffness and ligand density while the synthetic fibers will mimic the structure and the function of fibrous proteins found in the native extracellular matrix. Both the gel and the fiber components will be produced via a novel interfacial polymerization process that takes advantage of the rapid, bioorthogonal and highly efficient cycloaddition reaction between s-tetrazine (Tz) and trans-cyclooctene (TCO). The PIs will evaluate the potential of the synthetic matrix, combined with a dynamic culture device, in guiding the spatial differentiation of MSCs. The ultimate goal is to produce a multilayered construct with anisotropic features that reflect the microstructure of the targeted tissue. The proposed research program will provide a fertile training ground for undergraduate and graduate students, thus contributing to the continued growth of the biomedical engineering program at UD. The research project will also provide a platform for engaging and empowering early childhood teachers.

通过界面生物正交化学对干细胞行为进行空间控制（NSF DMR，生物材料计划# DMR-1506613）非技术性：组织工程有望创造现成的可植入组织或器官，以改善人类健康。功能组织的成功工程需要在体外​​重建细胞最初在体内所处的环境。在该项目中，将通过将具有所需空间梯度的凝胶材料与以重复方式显示生化信号的合成纤维相结合来创建仿生支架。各个组件和集成支架将使用一种利用超快、高效偶联反应的新颖工艺来生产。这样的过程允许对支架特性进行空间控制，而无需依赖外部的、潜在有毒的触发器或模板，从而能够轻松地将患者的细胞以3D方式并入支架中。细胞填充的支架将受到机械刺激以增强组织生长。最终目标是创造具有正确组织和适当功能的组织。这项工作将能够生产复杂的材料，以改善患有各种疾病的患者的生活质量，从而证明公众的支持是合理的。 PI 的外展和教育工作将有助于保持美国的全球竞争力。除了课程开发、学生培训之外，我们还将致力于吸引职前幼儿教师并为其赋权，他们将激励下一代科学家。技术：特拉华大学 (UD) 获得该奖项的目的是开发合成材料具有各向异性特征和空间梯度的矩阵可控制 3D 封装间充质干细胞 (MSC) 的行为，用于机械活性软组织工程。 PI 将通过将基于透明质酸 (HA) 的水凝胶与使用设计的单体从头生产的合成纤维相结合来实现这一目标。 HA 水凝胶将表现出基质刚度和配体密度的空间变化，而合成纤维将模仿天然细胞外基质中纤维蛋白的结构和功能。凝胶和纤维组分都将通过新型界面聚合工艺生产，该工艺利用了 s-四嗪 (Tz) 和反式环辛烯 (TCO) 之间快速、生物正交和高效的环加成反应。 PI 将评估合成基质与动态培养装置相结合在指导 MSC 空间分化方面的潜力。最终目标是生产具有各向异性特征的多层结构，反映目标组织的微观结构。拟议的研究项目将为本科生和研究生提供肥沃的训练基地，从而促进特拉华大学生物医学工程项目的持续发展。该研究项目还将提供一个吸引幼儿教师并为其赋权的平台。