Abstract

3D Modeling of Vascularized Barrier Tissues and Diseases For Preclinical Studies

Min Jae Song , Staff Scientist, National Center for Advancing Translational Sciences (NCATS)

In vitro three dimensional (3D) cellular models enable the study of multicellular interactions within functional tissue microenvironments. The enhanced physiological relevance of these complex 3D cellular models has opened the possibility of developing human-pathologically relevant disease assays for preclinical drug discovery and development studies. However, the increased cellular and structural complexity of these 3D cellular assays pose a significant technical challenge for their morphological and physiological validation, and use for pharmacological testing. Using 3D bioprinting techniques, we have established a robust and versatile method to engineer human vascularized tissues in a multiwell format. The bioprinting-based approach, used to biofabricate vascularized tissues, included a biodegradable polymer scaffold that enabled the addition of epithelia, in a transwell format. Several human barrier tissue models with vascularization were produced, including skin, peritoneal, and ocular tissues. Once 3D models of “healthy” tissues were biofabricated and validated, disease tissue models were developed by introducing disease-relevant chemical inducers or diseased cells, like cancer cells, into the “healthy” tissues. Treatments of the disease models with FDA approved drugs or drugs in clinical trials were able to correct the disease phenotypes. The structural, functional, and pharmacological validation of these tissues is critical to enable the use of these 3D models to accelerate the drug development process by providing pre-clinical data that it is more predictive of clinical outcomes.