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

迫切需要开发一种能够评估非养殖环境的孵化系统 侵犯性的。当应用于骨或软骨组织工程(TE)时，该仪器必须支持细胞 分化和构建生长和成熟，同时也显示磁共振成像(MRI) 兼容性，这将允许定期和非侵入性评估。如果没有这样的工具， 工程化骨和软骨组织的临床翻译受到工程评估困难的限制。 过程和结果，特别是组织的性能一致性和植入前的质量 构造。长期目标是开发一种与成像兼容的仪器来监测现场工程 组织生长和成熟。这一特定应用程序的目标是创建首个此类MRI- 用于间充质衍生工程构建物的兼容智能生物反应器作为模型系统 在为TE提供适当的生理条件和机械刺激的同时进行连续的MRI评估 构造。这项拟议研究的基本原理是，一旦建立了这样的工具，形态发生 工程化构造的演变和结果可以通过在 每天使用磁共振成像，从而在TE和再生医学领域产生了创新的方法。引导式 通过强大的初步数据，这一目标将通过追求三个具体目标来实现：1)评估 在电子孵化器中构建间充质来源的组织工程构建物；2)[研究MRI对 磁共振成像检测血流灌流刺激对间充质软骨的影响 可兼容的灌流生物反应器]；以及3)[研究MRI的灵敏度以检测变化的效果 在MRI兼容的超声生物反应器中对间充质衍生骨的超声刺激]。在……下面 第一个目标是用一个微控制器作为中央控制单元，形成一个封闭但自主的 受控和用户可配置的环境，同时允许MRI应用程序跟踪 建设发展新格局。间充质衍生的构造将被用作评估的模型系统。 在第二个和第三个目标下，电子孵化器将转变为一个用于TE构建的智能生物反应器 通过引入流动灌流或将其与压电式超声换能器集成。方法是 创新是因为它与目前可用的设计有实质性的不同，并将使 第一次，生理环境的调节；生长结构的评估；以及 使用磁共振对缺陷结构进行过滤。这项拟议的研究具有重要意义，因为它提供了一种转变 从生化分析到MRI的评估，它可以应用于其他工程化组织结构或 培养的组织/器官(例如，脑切片)。预计它还将有助于更广泛地理解 如何在生物反应器的帮助下更有效地在TE中应用成像方式。智能网的发展 用于监测工程化组织生长的成像兼容仪器有望在不久的将来问世。

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.