Bioreactor Core Facility

生物反应器核心设施

• 批准号: 8118207
• 负责人: JEAN F WELTER
• 金额: $ 14.5万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8118207
• 关键词: 3-Dimensional; Address; Area; Arts; Attention; Basic Science; Biomechanics; Bioreactors; Buffers; Cartilage; Cell Communication; Cells; Clinical; Complement; Complex; Computer Simulation; Computer Systems Development; 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; Technical Expertise; Temperature; Testing; Tissue Engineering; Tissues; Training; Universities; analog; base; 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。设计的三维组织 类似物旨在替代组织；此外，它们可以用作研究组织的研究工具 形态发生和复杂的细胞相互作用。 随着TE结构的大小的增加，质量传播限制的重要性迅速增长。在静态 文化可能会限制在几个mm3上的构建体大小。此时，生物反应器成为必不可少的 提供一个营养供应和清除废物的环境，但也有这样的环境条件 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；但是，这些设备仍然很昂贵 并且运作复杂性，关于给定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。此外，TE现在正在达到测试的阶段 一系列实验条件变得至关重要。及时完成此类实验 将需要大量反应堆。这为建立生物actor提供了明确的理由 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。 该计划项目赠款中提出的所有项目都将在某个点使用生物反应器。 Case Western Reserve University目前没有正式的生物反应器核心设施。这个的pi 核心设施及其同事开发了一个模块化生物反应器系统，以满足软骨的需求 组织工程。核心反应堆设计很简单，但高度可扩展，可以进行多种处理 和监视方式。除了该计划项目建议中详细介绍的项目外，该系统 它具有技术，科学和经济意义 从实验设计到设计和构建 生物反应器硬件的实际生物反应器操作。此外，这将使调查人员能够集中精力 他们对项目核心的基本科学问题的更多关注。 拟议的核心设施将强调汇总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反应器设施，包括： »计划项目调查人员的常规组织工程研究人员的最先进的生物反应器培养设施 �技术专长 - 此核心设施将为所有与生物反应器相关的训练有素且熟练的人 运营，从而提供最佳的技术专长。实验设计的帮助， 根据对系统的能力和局限性的了解以及项目特定的开发， 将提供对现有系统的需求驱动的扩展。 特定目的II：开发用于骨软骨组织工程的临床上有用的工具集。这项研究 组件将集中于开发系统的元素，以确保临床可伸缩性并最大化临床 公用事业。这些包括过程监视以及数据采集和控制。针对目标的特定方面 包括： „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。 �MRI方案开发以非侵入性监测植入物开发。 »整个生物反应器系统的详细计算机建模，包括流体动力学 以及与结构的气体/养分交换。 �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。 核心设施将提供所有这些服务和专家，从而释放PIS PIS以专注于实验 设计和结果解释。核心将由细胞，生物力学和形态完成 本提案中其他地方概述的核心，将通过收集有关要求的关键信息而受益 研究的组织类型，通过完善用于不同实验类型的计算机模型模板。这些数据 然后将从单个来源提供帮助核心用户设计实验。因此，我们期待 该设施将成为大量调查人员的宝贵资源。