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的空间控制（NSF DMR，生物材料计划＃DMR-1506613）非技术：组织工程有望建立现成的，可植入的组织或器官，以改善人类健康。功能组织的成功工程需要在体内重新创建的细胞最初驻留在体内的环境。在这个项目中，将通过将表现出所需空间梯度的胶状材料与合成纤维相结合，以重复性方式显示生化信号。单个组件和集成的支架将使用新型过程来利用超快，高效的耦合反应。这样的过程允许对脚手架特性进行空间控制，而不必依赖外部，潜在的有毒触发器或模板，从而使患者的细胞在3D中的支架中均能融合。细胞填充的支架将被机械刺激以增强组织的生长。最终目标是创建具有正确的组织和适当功能的组织。这项工作将使精致材料的生产能够改善患有各种疾病的患者的生活质量，从而证明公众支持是合理的。 PIS推广和教育工作将有助于维持美国的全球竞争力。除了课程发展外，学生培训，努力还将致力于激发下一代科学家的参与和授权，幼儿老师的能力。组织。 PIS将通过使用设计的单体将基于透明质酸（HA）的水凝胶与合成纤维的从头产生的合成纤维进行整合，从而实现这一目标。 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发现的纤维蛋白的结构和功能。凝胶和纤维成分都将通过新的界面聚合过程产生，该过程利用S-trazine（TZ）和跨环辛（TZ）（TZ）（TCO）之间的快速，生物色聚和高效的环加成反应。 PI将在指导MSC的空间分化时评估合成基质的潜力，并结合动态培养装置。最终目标是生产具有各向异性特征的多层构造，该构建体反映了目标组织的微观结构。拟议的研究计划将为大学生和研究生提供肥沃的培训场，从而为UD生物医学工程计划的持续增长做出了贡献。该研究项目还将为吸引和授权幼儿老师提供能力的平台。