Bioreactor Core Facility

生物反应器核心设施

• 批准号: 8309230
• 负责人: JEAN F WELTER
• 金额: $ 13.89万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8309230
• 关键词: 3-Dimensional; Address; Area; Attention; Basic Science; Biomechanics; Bioreactors; Buffers; Cartilage; Cell Communication; Cells; Clinical; Complement; Complex; Computer Simulation; Consensus; Core Facility; Data; Development; Devices; Economics; Elements; Engineering; Ensure; Environment; Environmental Monitoring; Equipment; Excision; Experimental Designs; Faculty; Feedback; Funding; Future; Gases; Health Services Research; Healthcare; Histocompatibility Testing; Homeostasis; Human Resources; Implant; Knowledge; Laboratories; Life; Magnetic Resonance Imaging; Modality; Monitor; Morphogenesis; Morphology; Nutrient; Process; Program Research Project Grants; Research; Research Personnel; Resources; Services; Source; Staging; Students; System; Systems Development; Technical Expertise; Temperature; Testing; Tissue Engineering; Tissues; Training; Universities; analog; base; cartilage repair; clinical application; data acquisition; design; design and construction; instrument; operation; osteochondral tissue; pressure; programs; protocol development; research study; tool; wasting

Bioreactor Core Facility Introduction and Specific Aims Tissue engineering (TE), i.e., the fabrication of living, 3-dimensional, functional tissue analogs, is a rapidly developing research area that has the potential to revolutionize healthcare. Engineered three-dimensional tissue analogs are intended to replace tissue; in addition, they can serve as research tools to investigate tissue morphogenesis and complex cell-cell interactions. The significance of mass-transport limitations grows rapidly with increasing size of a TE construct; in static culture it can become limiting at construct sizes over a few mm3. At this point, a bioreactor becomes essential to provide an environment in which nutrient supply and waste removal, but also environmental conditions such as pH, temperature, or pressure, can be monitored and controlled. Several bioreactor designs have been commercialized; however, these devices remain quite expensive and complex to operate, and there is little consensus as to what constitutes the best design for a given TE application. Investigators wishing to develop large-scale TE constructs as part of their research program must currently design or purchase their own equipment. Furthermore, TE is now reaching a stage in which the testing of arrays of experimental conditions is becoming critical. Completing such experiments in a timely fashion will require a large number of reactors. This provides a clear rationale for the establishment of a Bioreactor Core Facility, i.e., a laboratory dedicated to providing state-of-the-art technical, instrument, and professional development support, and specialized training of faculty, staff and students. All the projects proposed in this Program Project Grant will make use of a bioreactor at one point or another. Case Western Reserve University does not currently have a formal bioreactor core facility. The PI of this core facility and his co-workers has developed a modular bioreactor system to address the needs of cartilage tissue engineering. The core reactor design is simple, but highly extensible, to allow for a wide range of treatment and monitoring modalities. In addition to the projects detailed in this Program Project proposal, this system has proven itself in the context of other funded projects. It makes technical, scientific and economic sense to centralize all bioreactor-related steps of these projects, from experimental design, to design and construction of bioreactor hardware, to the actual bioreactor operation. Further, this will allow the investigators to focus more of their attention on the basic science questions that are central to their projects. The proposed core facility will emphasize service and core facility research components that are summarized in the following Specific Aims: Specific Aim I: to provide a full-service research bioreactor facility to each PPG project, including: ¿ State-of-the-art bioreactor culture facilities for Program Project investigators for routine tissue engineering ¿ Technical expertise - this core facility would provide trained and skilled personnel for all bioreactor related operations, thus providing the best possible technical expertise. Assistance in experimental design, based on knowledge of the capabilities and limitations of the system, and development of projectspecific, need-driven extensions to the existing system, will be provided. Specific Aim II: to develop a clinically useful toolset for osteochondral tissue engineering. This research component will focus on developing elements of a system that will ensure clinical scalability and maximize clinical utility. These include process monitoring, and data acquisition and control. Specific aspects to be targeted include: ¿ Bioreactor medium homeostasis, by online monitoring of environmental parameters and feedback control through medium flow rate and/or through the use of buffers. ¿ MRI protocol development to monitor implant development non-invasively. ¿ Implementation of detailed computer modeling of the bioreactor system as a whole, including hydrodynamics and gas/nutrient exchange with the construct. ¿ Development of disposable versions of the media-wetted bioreactor components for future clinical applications. The core facility will provide all these services and expertise, freeing the Project Pis to focus on experimental design and result interpretation. The core will be complemented by the Cell, Biomechanics, and Morphology cores outlined elsewhere in this proposal, and will benefit by gathering critical information on the requirements of tissue type investigated, by perfecting computer model templates for different experiment types. These data will then be available from a single source to aid core users in designing their experiments. We therefore anticipate that this facility will become an invaluable resource to a significant number of investigators.

生物反应器核心设施 介绍和具体目的 组织工程（TE），即生存的制造，三维功能组织类似物，是一个迅速的 开发有可能改变医疗保健的研究领域 类似物旨在替代组织； 形态发生和复杂的细胞相互作用。 质量限制的意义从静态结构的尺寸迅速增长 在这一点上，培养可能会限制在几个MM3上。 提供环境供应和废物清除，也可以提供此类环境条件。 作为pH，温度或压力，可以监视和控制。 几种生物反应器设计已商业化； 并且要运行复杂，并且对于给定的TE应用程序的最佳设计几乎没有共识。 希望开发大型TE结构作为其研究计划的一部分的调查人员必须 目前设计或购买自己的设备。 实验条件的阵列至关重要。 将需要大量的反应堆。 核心设施，即致力于提供最先进的技术，工具和专业的实验室 发展支持以及教职员工和学生的专门培训。 所有项目计划项目赠款都将利用点或另一个项目的生物反应器。 Case Western Reserve University目前没有正式的生物反应器核心设施。 核心设施及其同事开发了一个模块化生物反应器系统，以增加软骨的需求 组织工程。 和监视模式。 在其他资助的项目的背景下，已经证明了这一点。 从实验设计到设计和构建，要集中项目的所有与生物反应器相关的步骤 生物反应器硬件，进一步的生物反应器。 他们对中央项目的基本科学问题的更多关注。 支撑的核心设施将强调该地区总结的服务和核心设施研究组件 在以下具体目的中： 特定目的I：为每个PPG项目提供全方位服务的研究生物学配置，包括： 挥之不去f-F-the Bioractor文化文化培养设施针对常规组织工程的计划项目调查员 挥之不去技术专长 - 该核心设施将训练熟练的人员伪造人员锻炼者相关 运营，从而提供最佳的技术专长。 根据对系统的能力和局限性的了解以及项目特定的发展的知识， 需求驱动的扩展名将提供现有系统。 特定目标II：为骨软骨组织工程开发临床上有用的工具集。 组件将集中于开发系统的元素，以确保临床和最大化临床 实用程序包括过程监控以及数据采集和控制。 包括： 挥之不去生物反应器中等稳态，通过在线监视环境参数和反馈控制 通过中等流量和/或通过使用缓冲区。 挥之不去MRI协议开发以非侵入性监测植入物的开发。 挥之不去生物反应器系统系统的实施计算机建模尽可能高 以及与结构的气体/养分交换。 挥之不去开发用于未来临床应用的媒体润湿生物反应器成分的一次性版本。 该设施将提供所有这些服务和专业知识，使PIS释放PIS以专注于实验 设计和结果解释。 核心概述了该提案中的其他内容，并将通过收集有关要求的关键信息而受益 通过为不同类型的计算机模型进行了研究 然后，将从单个来源提供帮助核心用户设计其实验 该设施将成为大量调查人员的武土资源。