Magnetic 3D Bioprinting, The Next Step in High-Throughput Compound Screening and Translational Applications

The limited relevance of non-human tissues and the need to reduce the dependence on animal-intensive tests define an unmet need for in vitro assays with fewer ethical challenges and the potential for needed translational capabilities. Thus, there is a demand for an in vitro assay that is predictive of in vivo drug response, uses human cells, and is adaptable to high-throughput screening and clinical applications. To meet such need, biomedical research has gravitated towards 3D cell culture for models and assays that accurately represent in vivo tissue. Challenges in 3D cell culture, both technical/practical and analytical, exist as increased throughput and miniaturization of 3D cultures can make handling and imaging difficult. Towards that end, we developed a platform, magnetic 3D bioprinting (m3D), that addresses key technical difficulties of 3D cell culture. As a result from a collaboration with MD Anderson Cancer Center, we will show comparable compound response, tissue morphology, and gene expression between m3D and a PDX mouse model generated from the same original breast tumor and treated with the same panel of drugs. Next, with The Scripps Research Institute and Cold Spring Harbor Laboratory, we validated m3D as a high-throughput screening platform using four patient-derived pancreatic cancer-associated cell types against 3,290 of FDA approved compound library. Here, we compared and identified clear differences between screens performed in 2D versus 3D. Finally, during this screen, we identified a single compound which was only active in cells cultured in 3D and is currently under Phase I trial for pancreatic cancer.