Biofabrication of engineered 3D tissues for disease modeling and drug discovery

Biofabrication of architecturally defined and physiologically relevant human tissues is emerging as a key technology for disease modeling and drug discovery. The expectation is that these physiologically relevant engineered 3D tissues produced with human primary or iPSC-derived cells will be more clinically predicative assay platforms to test small molecules during drug discovery than current 2D cellular models. The vision is that engineered 3D tissue models will help reduce the use of animal in drug discovery and make the process of drug discovery faster, cheaper, and more efficient.

Tissue bioabrication integrates advances in tissue engineering technologies and cell biology, with the development of three-dimensional (3D) bioprinters, biocompatible polymers and hydrogels, and methods to validate the morphology and function of human tissues. Rapid, scalable, and reliable biofabrication of architecturally and physiologically defined functional human tissues in multiwell-plate platforms for drug testing integrates five emerging technologies: 1) bioprinters with precise XYZ control to reproducibly fabricate tissues with defined 3D geometries; 2) biocompatible hydrogels to support the 3D structure of tissue-embedded cells; 3) platforms that enable the delivery of mechanical and chemical cues to the cells seeded in the biofabricated tissue; 4) ability to obtain autologous cells from patients, including human iPSCs; and 5) the ability to quantitatively characterize the morphology and functionality of biofabricated tissues using both invasive and non-invasive technologies such as high resolution fluorescence confocal/multiphoton microscopy and image analysis techniques.

The NCATS 3D Tissue Bioprinting Laboratory (3DTBL) has the capabilities to generate live human tissues that closely resemble the defined anatomical architecture of native human tissues, including vasculature and immune cells. The NCATS 3DTBL is bioprinting engineered 3D tissues in multiwell plate format, validating the tissues using histology, fluorescence imaging and scRNAseq, and developing physiologically relevant quantitative assay readouts to enable screening of drug libraries. The student will have an opportunity to be an integral member of a team within the NCATS 3DTBL to learn and use these technologies to develop a disease tissue model and implement drug screens to find potential new therapeutics for that disease.

We are currently developing engineered 3D tissue models of skin, lung, skeletal muscle, neuronal circuits, and the blood brain barrier. The student will be able to work on any of these models based on her/his interest(s).