Abstract

Bioprinted in vitro Models in Drug Developments - Perspective from Pharmaceutical Industry

Annie Moisan, Lab Head, Roche Pharmaceuticals

Nephrotoxicity is a major side effect of drugs, accounting for approximately 20% of community and hospital-acquired acute renal failure. These failures stem from extensive use of animal models in preclinical testing that are not sufficiently predictive of the human response. To address this challenge, we present a bioprinting method for creating functional 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than three months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen at physiological shear stresses. These engineered 3D proximal tubules exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D surfaces with or without perfusion. Additionally, curved regions of the convoluted tubule uptake albumin more than nearby straight regions. Lastly, upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. This in vitro model system allows customization by printing perfusable vasculature and multiple cell types in predefined locations, enabling both drug screening and drug toxicity mechanistic studies at user-defined levels of complexity.