Bioprinted Multi-Composition Array Mimicking Tumor Microenvironments to Evaluate Drug Efficacy with Multivariable Analysis.

Abstract

Current organ-on-a-chip technologies confront limitations in effectively recapitulating the intricate in vivo microenvironments and accommodating diverse experimental conditions on a single device. Here, a novel approach for constructing a multi-composition tumor array on a single microfluidic device, mimicking complex transport phenomena within tumor microenvironments (TMEs) and allowing for simultaneous evaluation of drug efficacy across 12 distinct conditions is presented. The TME array formed by bioprinting on a microfluidic substrate consists of 36 individual TME models, each characterized by one of three different compositions and tested under four varying drug concentrations. Notably, the TME model exhibits precise compartmentalization, fostering the development of self-organized vascular endothelial barriers surrounding breast cancer spheroids affecting substance transport. Multivariable screening and analysis of diverse conditions, including model complexity, replicates, and drug concentrations, within a single microfluidic platform, highlight the synergistic potential of integrating bioprinting with microfluidics to evaluate drug responses across diverse TME conditions comprehensively.