(M-487) Tissue Regenerator: Engineering tissue templates with integrated quality monitoring.

Introduction:: The loss of muscle volume due to tumor ablation or traumatic injuries is a major challenge in modern societies, often resulting in disabilities in patients. In the USA, the annual cost of treating skeletal muscle injuries was estimated to be 176 billion dollars, with long-term expenditures potentially exceeding twice that amount. Techniques to reconstruct or mimic donor tissue are urgently needed but are still far from reaching clinical stage. Initial high expectations for tissue engineering (TE) were disappointing as the progress of implementing TE products into clinical and commercial endpoints has been slow, yielding modest results. This is contradicted by compelling advances made in highly defined laboratory environments. Numerous difficulties and technical barriers still need to be overcome to enable a successful clinical translation. One possible TE technique is top-down de- and recellularization, which allows the production of acellular templates for de novo regeneration or use as tissue patches to compensate for huge volumetric muscle loss in reconstructive surgery. However, an urgent requirement is to produce standardized acellular muscle templates, as well as on-line quality monitoring parameters to control template maturation during recellularization.


Materials and Methods:: A novel TE platform called Tissue Regenerator was created and developed to fill this gap. As the first step toward a second-generation de- & recellularization all-in-one device, it combines a bioreactor and process engineering technology, primarily, but not exclusively for decellularization and recellularization experiments. The system includes an optical platform that rotates around the vessel with the ability to take images through a mounted camera, or through taking a transmissive or reflective spectrum of the sample with two opposed lenses. Further, a biomechanics module supports active electromagnetic stimulation, as well as passive template actuation for maturation and training. An implemented hydrostatic pressure sensor measures the vascular perfusion pressure at all times to ensure vascular patency.


Results, Conclusions, and Discussions:: New possible on-line quality monitoring parameters were examined utilizing techniques from biomechanics and biophotonics. These include hydrostatic vascular pressure, continuous passive biomechanics, discrete passive biomechanics, diffuse reflectance spectroscopy, transmission spectroscopy, and 3D representation. A well-established protocol utilizing 0.1% sodium dodecyl sulfate (SDS) in de-ionized water was used to reduce additional variables. Novel parameters were validated via perfusion-decellularization through the main feeding artery of an M. gastrocnemius medialis and categorized according to their suspected usefulness in decellularization quality monitoring or in process control. The Tissue Regenerator represents a first step towards adaptive TE quality monitoring in an otherwise challenging scientific environment and may pioneer TE protocol standardization.


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