Biofabrication of 3D tissue models of diseases for drug discovery
Biofabrication of architecturally defined and physiologically relevant human tissues is emerging as a key technology for drug discovery. The expectation is that 3D biofabricated tissues produced with human iPSC-derived cells will provide functionally and physiologically relevant assay platforms to test small molecules during drug discovery, and help narrow the current gaps between current simplistic in-vitro cell assays, non-predictive in-vivo animal models, and human clinical trials.
The NCATS 3D Tissue Bioprinting Laboratory has the capabilities to generate live human tissues that closely resemble the defined anatomical architecture of native human tissues and organs, and can be used for drug screening and discovery. The 3D Tissue Bioprinting Laboratory is bioprinting 3D tissues in multiwell plate platforms and develop physiologically relevant quantitative assay readouts on these 3D tissue models to enable tissue-in-a-dish models and screening of drug libraries.
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 student will have an opportunity to be an integral member of a team within the NCATS 3D Tissue Bioprinting Laboratory 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 models of normal retina, skin, ovarian cancer metastasis on the peritoneum, and neurovascular unit, and using this basic 3D tissue models to induce a disease phenotypes, such as age-related macular degeneration for retina and psoriasis and atopic dermatitis for skin, and eventually test drugs that correct the disease phenotype in the context of the tissue. The student will be able to work on any of these models based on her/his interest(s).