In vitro construction of lung cancer organoids by 3D bioprinting for drug evaluation

Abstract

The construction of tumor model plays a crucial role in preclinical drug evaluation. However, traditional two-dimensional (2D) monolayer cell models are unable to accurately predict drug activity in vivo, and animal models have species differences and ethical issues. Herein, a droplet-based 3D bioprinting strategy is established to construct lung cancer organoid arrays for drug evaluation. The bioink system is based on sodium alginate (SA, used to crosslink with Ca2+), hyaluronic acid (HA, used to improve gel viscoelasticity and printability), and arginine-glycine-aspartic acid peptide (RGD, used to improve cell adhesion). Hundreds of organoids with 3D multicellular spherical structures are produced in batches after post-printing culture. Compared with 2D monolayer culture models, 3D organoids show higher cell activity and functional expression of P-CK, ProSP-C, MUC1 and Caveolin-1, as well as higher anticancer drug resistance and IC50. This strategy will provide insights into the field of organoid modeling, high-throughput and personalized drug screening.