Organ-on-a-chip for dynamic tumor drug resistance investigation

Abstract

Drug resistance continues to be the main limiting factor in the cure of cancer patients. Herein, an organ-on-a-chip platform based on inverse opal scaffold was proposed to generate tumor cell spheroids and study resistance dynamically. The relevant inverse opal scaffold with desired tridimensional porous structure was prepared by negatively replicating the assembled microfluidic droplet template. Benefitting from the ordered and uniform porous structure of the inverse opal scaffolds, hepatoma cells could aggregate in the pores of the scaffold and form large amounts of homogeneous hepatoma cell spheroids. The proposed liver tumor-on-a-chip was established by integrating the inverse opal scaffolds with a well-designed gradient microfluidic chip. The liver tumor models with varying degrees of drug-resistant phenotypes were realized by simply gradient injection of hepatoma parental and resistant cells into the microfluidic chip. Based on the resultant system, we have obtained the dynamic drug resistance performance of different tumor stages and diverse medication periods, which will provide extremely significant preclinical data for drug therapy of tumors. These features make the proposed organ-on-a-chip platform a valuable candidate for preclinical drug resistance evaluation.