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.
