Assessment of Mechanical Stimulation of Mesenchymally Derived Constructs in an MRI Bioreactor

MRI 生物反应器中间充质衍生结构的机械刺激评估

• 批准号: 9813193
• 负责人: Shadi F Othman
• 金额: $ 35.31万
• 依托单位: UNIVERSITY OF THE PACIFIC-STOCKTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9813193
• 关键词: Adverse effects; Biochemical; Biological Assay; Biological Models; Biomedical Research; Bioreactors; Bone Tissue; Brain; Cartilage; Cell Differentiation process; Cell Proliferation; Cells; Chondrogenesis; Clinical Research; Data; Development; Effectiveness; Engineering; Ensure; Environment; Evaluation; Evolution; Exhibits; Extracellular Matrix; Fiber; Future; Goals; Growth; Human; Image; Implant; In Situ; In Vitro; Incubators; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Measurement; Mechanical Stimulation; Mechanical Stress; Mechanics; Mesenchymal; Methods; Modeling; Monitor; Morphogenesis; Natural regeneration; Organ; Osteogenesis; Outcome; Performance; Perfusion; Periodicals; Periodicity; Physiologic pulse; Physiological; Process; Public Health; Publishing; Regenerative Medicine; Regulation; Research; Slice; Stimulus; Supporting Cell; System; Testing; Time; Tissue Engineering; Tissues; Transplantation; Ultrasonic Transducer; Ultrasonography; Uncertainty; Visual; Work; base; bone; bone engineering; bone loss; clinical translation; design; imaging modality; implantation; improved; innovation; instrument; magnetic field; novel; preimplantation; quantitative imaging; repaired; tool

There is an urgent need to develop an incubation system capable of assessing a cultured environment non- invasively. As applied to bone or cartilage tissue engineering (TE), this instrument must support cell differentiation and construct growth and maturation while also exhibiting magnetic resonance imaging (MRI) compatibility, which would allow for periodic and non-invasive evaluation. Without such an instrument, the clinical translation of engineered bone and cartilage tissue is limited by the difficulties of assessing engineering processes and outcomes, specifically the performance consistency and pre-implantation quality of tissue constructs. The long-term goal is to develop an imaging-compatible instrument to monitor in situ engineered tissue growth and maturation. The objective of this particular application is to create a first-of-its-kind MRI- compatible smart bioreactor for mesenchymally derived engineered constructs as a model system that enables continuous MRI assessment while offering proper physiological conditions and mechanical stimuli for TE constructs. The rationale for the proposed research is that once such an instrument is built, the morphogenesis evolution and outcome of engineered constructs can be visualized through volumetric quantitative images on a daily basis using MRI, resulting in innovative approaches to the field of TE and regenerative medicine. Guided by strong preliminary data, this objective will be accomplished by pursuing three specific aims: 1) assess mesenchymally derived tissue engineered constructs in the e-incubator; 2) [Research the sensitivity of MRI to detect the effectiveness of a perfusion flow stimulation on mesenchymally derived cartilage in an MRI compatible perfusion bioreactor]; and 3) [Research the sensitivity of MRI to detect the effect of varying ultrasound stimulation on mesenchymally derived bone in an MRI compatible ultrasound bioreactor]. Under the first aim, a microcontroller will be used as a central control unit to form an enclosed but autonomously controlled and user-configurable environment while simultaneously allowing applications of MRI to track construct development. Mesenchymally derived constructs will be used as a model system for evaluation. Under the second and third aims, the e-incubator will be transformed into a smart bioreactor for TE constructs by introducing flow perfusion or integrating it with a piezoelectric ultrasound transducer. The approach is innovative because it represents a substantive departure from the currently available designs and will enable, for the first time, the regulation of the physiological environment; assessment of growing constructs; and filtering of deficient constructs using MRI. The proposed research is significant because it offers a shift in TE assessment from biochemical assays to MRI and it can be applied to other engineered tissue constructs or cultured tissues / organs (e.g., brain slices). It is also expected to contribute to the broader understanding of how imaging modalities can be applied in TE more effectively with the aid of bioreactors. Development of an imaging-compatible instrument to monitor engineered tissue growth is expected in the near future.

迫切需要开发一种能够评估培养环境的培养系统， 侵入性地当应用于骨或软骨组织工程（TE）时，该仪器必须支持细胞增殖， 分化和构建体生长和成熟，同时还表现出磁共振成像（MRI）， 兼容性，这将允许定期和非侵入性评估。如果没有这样的文书， 工程化骨和软骨组织的临床转化受到评估工程化的困难的限制 过程和结果，特别是组织的性能一致性和植入前质量 结构。长期目标是开发一种成像兼容的仪器来监测原位工程 组织生长和成熟。这项特殊应用的目的是创造一个首创的MRI- 用于间充质衍生的工程化构建体的兼容智能生物反应器作为模型系统， 连续MRI评估，同时为TE提供适当的生理条件和机械刺激 结构。这项研究的基本原理是，一旦建立了这样的仪器， 工程化构建体的进化和结果可以通过在一个或多个细胞上的体积定量图像来可视化。 每天使用MRI，导致TE和再生医学领域的创新方法。指导 通过强有力的初步数据，这一目标将通过追求三个具体目标来实现：1）评估 在e-培养箱中的间充质来源的组织工程构建物; 2）[研究MRI对 在MRI中检测灌注流刺激对间充质衍生软骨的有效性 相容的灌注生物反应器];和3）[研究MRI的灵敏度，以检测不同灌注生物反应器的影响]。 在MRI兼容的超声生物反应器中对源自间充质的骨进行超声刺激]。下 第一个目标，微控制器将被用作中央控制单元，以形成封闭但自主的 受控和用户可配置的环境，同时允许MRI应用程序跟踪 建设发展。间充质衍生的结构将用作评价的模型系统。 根据第二和第三个目标，电子孵化器将转变为TE结构的智能生物反应器 通过引入流动灌注或将其与压电超声传感器集成。该方法是 创新性是因为它代表了与当前可用设计的实质性偏离， 第一次，调节生理环境;评估生长结构;和 使用MRI过滤缺陷构建体。拟议的研究意义重大，因为它提供了TE的转变 从生物化学测定到MRI的评估，并且它可以应用于其他工程化组织构建体或 培养的组织/器官（例如，脑切片）。它还将有助于更广泛地了解 如何在生物反应器的帮助下更有效地将成像模式应用于TE。的研制 在不久的将来，有望开发出与成像兼容的仪器来监测工程化组织的生长。