MRI: Development of a Bio-Pick and Place Instrument for the Fabrication of 3D Organs from Complex Shaped Living Building Parts

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PI: Morgan, JeffreyProposal: 1428092Title: MRI: Development of a Bio-Pick and Place Instrument for the Fabrication of 3D Organs from Complex Shaped Living Building PartsSignificanceThe Bio-Pick & Place instrument will make Brown University a world leader in 3D organ fabrication. In addition to being a showcase instrument for bioengineering, the Bio-P&P will be one-of-a-kind with unique technical capabilities. There is already a strong well-funded community of tissue engineers at Brown in the School of Engineering, the Division of BioMed and affiliated hospitals that would benefit from this instrument. There are other faculty in need of a replacement for animals and new complex test beds to evaluate the toxicity of chemicals, nanomaterials, new therapies and drug delivery. This unique instrument will aid in recruiting future faculty and will make possible new collaborations and new funding opportunities (NIH, NSF, DOD, industry). As a world-class instrument, it will foster collaboration with academics, clinicians and industry. Development of the instrument will generate new intellectual property and further strengthen the synergism that the Center for Biomedical Engineering has created between BioMed and Engineering. The instrument will significantly enhance the training infrastructure including; a new generation of instrumentalists facile in the use of engineering principles for the fabrication of a wide range of living materials, a new generation of scientists, engineers, and physicians using 3D living structures to investigate questions in developmental biology, the reduction of the use of animals in research, as well as the enhancement of tissue engineering research, toxicology testing, drug discovery, production of therapeutic proteins and clinical applications.Technical DescriptionThe major engineering challenge to the field of tissue engineering is the in vitro fabrication of large solid organs with high densities of living cells. Diffusion of oxygen, nutrients and removal of metabolic waste products limit current engineered tissues to thicknesses of ~100-200ìm in order to maintain cell viability. Natural organs are much larger and contain a branching vascular supply that perfuses the entire organ and ensures all cells are close to blood vessels. As the field of tissue engineering struggles with this limitation, the field of induced pluripotent (iPS) stem cells is providing a plentiful source of immune-matched cells of a variety of tissues and organs. The community does not yet have a means for the in vitro fabrication of large 3D organs and tissues from this source of cells. An instrument with this capability would have a worldwide impact in the field of tissue engineering. Such an instrument would establish new paradigms in the fields of biofabrication, biomanufacturing and would build new 3D models for research useful in any number of basic as well as applied fields. The major challenges in this area of organ fabrication are engineering in nature, albeit ones that must be informed by biology. The Bio-P&P instrument will assemble large 3D tissues/organs layer-by-layer using a controllable low level suction head to pick up living building parts and place them onto other living building parts in precise locations, while maintaining perfusion as parts fuse and the living structure is built. This is a versatile building platform that can grip multi-cellular building parts of any size, shape and cell type. The PIs have produced large living building parts in the shape of a honeycomb and, when stacked, the aligned lumens of these honeycomb parts will form channels that enable perfusion of the organ under construction. Success