EAGER: High-Throughput Bioprinting of Vascularized Living Tissue

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The ability to fabricate vascularized living tissues would enable critical advances in drug screening, tissue repair and regeneration. Tissue engineering has traditionally relied on the use of acellular scaffolds. However, this approach vastly limits the size and complexity of the tissues that can be created due to the lack of stable, perfusable vasculature and the inability to replicate intricate multicellular configurations. Vasculature networks are central to living tissues, since all cells must reside within several hundred micrometers of a nutrient supply to survive. This award supports scientific investigations on a new additive manufacturing process for fabricating three-dimensional, vascularized living tissues composed of cells, extracellular matrix, and embedded blood vessels. Results from this research will enable broader use of 3D living tissues in the pharmaceutical industry for drug safety and toxicity screening and, ultimately, in the medicine for tissue repair and regeneration.This research will establish the fundamental scientific understanding required for bioprinting of vascularized living tissue at organ scale. The complex interplay between cells, extracellular matrix, and vasculature in printed tissues will be determined. These relationships will be established by quantifying cell viability via live/dead staining as a function of varying cell type, concentration, and extracellular matrix composition. The effects of vascular network architecture, including blood vessel size, spacing, and degree of branching, on cell viability and function will also be quantified by live/dead and, concurrently, barrier function of the vascular channels will be measured by a standard leak test as a function of different architectural motifs. Finally, the relationship between nozzle size, design, and printing speed will be determined for cell-laden inks of varying cell type, concentration, and extracellular matrix composition to identify the requisite conditions that promote maximum cell viability, as determined by live/dead staining, during bioprinting and perfusion over long time periods.