TR&D-2: Sensor Enabled Scaffolds

TR

• 批准号: 10554851
• 负责人: JEAN F WELTER
• 金额: $ 16.94万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10554851
• 关键词: 3D Print; Affinity; Behavior; Binding; Biochemical; Biocompatible Materials; Biological; Bioreactors; Biosensor; Calibration; Cartilage; Cell Density; Cell division; Cell physiology; Cell surface; Cell-Matrix Junction; Cells; Cellular Metabolic Process; Chemistry; Citrates; Collagen; Consumption; Cues; Detection; Development; Devices; Diffusion; Dyes; Engineering; Ensure; Excision; Exhibits; Feedback; Fiber; Fiber Optics; Fluorescence; Gel; Generations; Germ Cells; Glass; Glucose; Light; Lighting; Link; Location; Mammalian Cell; Measurement; Measures; Metabolic; Metabolic Marker; Metabolism; Methods; Molecular; Molecular Conformation; Monitor; Nutrient; Optics; Oxygen; Performance; Plague; Process; Production; Property; Reagent; Reporter; Reproducibility; Resistance; Signal Transduction; Skin; Source; Specificity; Spottings; Standardization; Structure; Surface; System; Technology; Thick; Thinness; Time; Tissue Differentiation; Tissue Engineering; Tissue Microarray; Tissue constructs; Tissues; Validation; Variant; Work; aptamer; base; bioink; biomaterial compatibility; bioscaffold; cell determination; complex data; data acquisition; data streams; design; detection limit; detector; in vitro testing; innovation; instrument; novel; process optimization; prototype; scaffold; sensor; stability testing; tissue support frame; uptake; wasting

Project Summary/Abstract: During the process of fabricating an engineered tissue construct, it is critical to be able to assess the initial cell seeding and subsequent cell functions in real time. This TR&D will focus on the development of biosensor tech- nology that will leverage the widespread use of scaffolds in tissue engineering to produce sensor-enabled scaf- folds in different materials and configurations to serve our CPs/SPs. Our key innovation is to incorporate sensing functions into the scaffolds that can be used to monitor multiple specific biological properties dynamically and longitudinally, thus enabling the potential to control and modify cell seeding, nutrient exchange, metabolic waste removal and differentiation cues in real-time. We will accomplish this in two Specific Aims: Specific Aim 1: Generation of sensing scaffolds to monitor and automate cellular seeding. During the automated fabrication process of a TE construct, it is critical to be able to assess cell attachment in real-time in order to validate the seeding process or take remedial action if called for. Because different scaffold biomaterials and syntheses provide different microenvironmental cues for cells, assessing the attachment and distribution of cells within the scaffold during TEMP assembly can help optimize the process. We will design beacon-type aptamers that bind and react to cell whole cells or alternately to cell surface molecules and are therefore usable as short- term sensors in this application. The aptamers will have a molecular beacon-type of reporter chemistry that will be activated by conformational changes upon binding their target cell and will provide a fluorescent feedback signal proportional to the number of cells seeded to the scaffold. Our aptamer sensor that can be attached to or integrated into scaffolds/biomaterials/bioinks. Variations of the technology will include optic light guide aug- mented scaffolds to assess the interior of thick structures. Specific Aim 2: Sensor platforms to measure O2, glucose and lactate. O2, glucose and lactate are 3 key markers of metabolic activity. Monitoring of these is essential during differentiation and/or maturation of tissues to deter- mine both their functionality and biochemical quality, and to, again, provide signals for remedial action if needed. We will develop O2, glucose, and lactate optodes using novel chemistries, and integrate them with scaffolds in a variety of application-specific ways to measure levels of O2, glucose, and lactate in the tissue interior, at the tissue surface and eventually in the bulk medium. We will also develop a system to measure oxygen uptake rate at the surface of the engineered construct. The sensors will use biocompatible materials and will be integrated into the scaffolds or reversibly attached to them using novel micro-anchors. The sensors will be tested for stability during scaffold storage, and for biocompatibility and stability during tissue differentiation and maturation.

项目摘要/摘要： 在制造工程化组织结构的过程中，能够评估初始细胞是至关重要的 实时播种和后续单元功能。本次研发将重点关注生物传感器技术的发展-- Nology将利用组织工程中广泛使用的支架来产生传感器使能的SCAF- 折叠使用不同的材料和配置，以满足我们的CPS/SPS。我们的关键创新是将传感器 可用于动态监测多个特定生物属性的支架中的功能 纵向上，从而使控制和修改细胞接种、营养交换、代谢废物的潜力成为可能 实时删除和区分提示。我们将通过两个具体目标来实现这一目标： 具体目标1：产生用于监测和自动化细胞播种的传感支架。在自动化过程中 在TE结构的制造过程中，能够实时评估细胞附着性是至关重要的，以便 验证种子设定过程或在需要时采取补救措施。因为不同的支架生物材料和 合成为细胞提供不同的微环境线索，评估细胞的附着和分布 在临时组装过程中脚手架内可以帮助优化工艺。我们将设计信标类型的适配子 结合并与整个细胞反应或交替与细胞表面分子反应，因此可用作短链- 此应用程序中的术语传感器。适配子将具有分子信标类型的报告化学，它将 在结合靶细胞时被构象变化激活，并将提供荧光反馈 信号与接种到支架上的细胞数量成正比。我们的适体传感器可以连接到或 集成到支架/生物材料/生物墨水中。这项技术的变种将包括光学光导8月- 多层脚手架，用于评估厚结构的内部。 具体目标2：测量氧气、葡萄糖和乳酸的传感器平台。氧气、葡萄糖和乳酸是三个关键的标志物 新陈代谢活动。在组织分化和/或成熟过程中监测这些是必不可少的，以阻止- 挖掘它们的功能和生化质量，并再次提供信号，如果需要的话，采取补救行动。 我们将使用新的化学方法开发氧气、葡萄糖和乳酸光敏元件，并将它们与支架集成在一起 多种特定用途的方法来测量组织内部的O2、葡萄糖和乳酸水平， 组织表面，并最终在散体介质中。我们还将开发一种系统来测量氧气摄取率 在工程结构的表面。传感器将使用生物兼容材料，并将被集成 进入支架或使用新型微锚可逆地附着在支架上。传感器将接受稳定性测试 在支架储存期间，以及在组织分化和成熟过程中的生物相容性和稳定性。