Abstract

The Bio-Pick, Place and Perfuse (Bio-P3): A New Instrument for Building Living Tissue

Jeffrey Morgan, Professor of Medical Science and Engineering, Brown University

First reported in 2005, 3D bio-printers that dispense single drops of living cells along with a bio-glue captured the imagination as a new additive manufacturing technology that might someday print organs. However, the grand challenge of fabricating large living structures with cell density akin to native organs (liver, kidney) and sustaining the viability and functionality of these structures prior to transplantation has not yet been achieved. New technologies are still needed. By adapting the principles of pick & place machines used in the high speed assembly of electronics, we have developed a new instrument; the Bio-Pick, Place, and Perfuse (Bio-P3). Unlike bio-printers, the Bio-P3 uses prefabricated living parts and operates submerged under the nutrient culture medium needed to sustain viability of the tissue under construction. The Bio-P3 uses fluid suction to pick up, transport and precisely deposit layer-by-layer large living parts on a build stage. Each living part is prefabricated by seeding cells into micro-molded hydrogels wherein the cells self-assemble into microtissues with cell densities equal to that of normal organs and geometries predetermined by the micro-mold design. When stacked by the Bio-P3, these layers of prefabricated microtissues fuse without the use of a bio-glue to form a macrotissue. The resulting macrotissue, with organ-like cell density, is continuous perfused with culture medium to help meet the metabolic demands of the tissue. The Bio-P3 is a first-generation device with particular utility in solid organ tissue engineering, as it precisely assembles high-density microtissue subunits in a manner that permits perfusion of the growing structure.