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

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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.