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： 在制造工程组织结构的过程中，能够评估初始细胞至关重要 实时播种和随后的细胞功能。该研发将重点关注生物传感器技术的开发 技术将利用组织工程中广泛使用的支架来生产具有传感器功能的支架 采用不同的材料和配置折叠以服务于我们的 CP/SP。我们的关键创新是将传感技术融入 功能融入支架中，可用于动态监测多种特定的生物特性， 纵向，从而能够控制和修改细胞播种、营养交换、代谢废物 实时去除和分化提示。我们将通过两个具体目标来实现这一目标： 具体目标 1：生成传感支架以监测和自动化细胞接种。在自动化期间 在 TE 构建体的制造过程中，能够实时评估细胞附着至关重要，以便 验证播种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 TEMP 组装期间在支架内放置有助于优化流程。我们将设计信标型适体 与细胞全细胞或细胞表面分子结合并发生反应，因此可用作短 本应用中的术语“传感器”。适体将具有分子信标型报告化学物质， 结合靶细胞后构象变化被激活，并提供荧光反馈 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。该技术的变体将包括光学光导增强器 支撑脚手架来评估厚结构的内部。 具体目标 2：测量 O2、葡萄糖和乳酸的传感器平台。 O2、葡萄糖和乳酸是 3 个关键标志物 的代谢活动。在组织分化和/或成熟过程中对这些进行监测至关重要，以防止 挖掘它们的功能和生化质量，并在需要时再次提供采取补救措施的信号。 我们将使用新型化学物质开发 O2、葡萄糖和乳酸光极，并将它们与支架集成在一起 多种特定于应用的方法来测量组织内部的 O2、葡萄糖和乳酸水平 组织表面并最终进入本体培养基。我们还将开发一个测量摄氧率的系统 在工程结构的表面。传感器将使用生物相容性材料并将被集成 进入支架或使用新型微锚可逆地连接到支架上。传感器将进行稳定性测试 支架储存期间，以及组织分化和成熟过程中的生物相容性和稳定性。