Biopatterning of 3D cellular model by contactless magnetic manipulation for cardiotoxicity screening

Abstract

Patterning cells to create three-dimensional (3D) cell culture models by magnetic manipulation is a promising technique, which is rapid, simple, and cost-effective. This study introduces a new biopatterning approach based on magnetic manipulation of cells with a bioink that consists alginate, cells, and magnetic nanoparticles. Plackett-Burman and Box-Behnken experimental design models were used to optimize bioink formulation where NIH-3T3 cells were utilized as a model cell line. The patterning capability was confirmed by light microscopy through 7 days culture time. Then, biopatterned 3D cardiac structures were formed using H9c2 cardiomyocyte cells. Cellular and extracellular components, F-actin and collagen Type I, and cardiac-specific biomarkers, Troponin T and MYH6, of biopatterned 3D cardiac structures were observed successfully. Moreover, Doxorubicin (DOX)-induced cardiotoxicity was investigated for developed 3D model, and IC50 value was calculated as 8.1 μM for biopatterned 3D cardiac structures, which showed higher resistance against DOX-exposure compared to conventional two-dimensional cell culture. Hereby, developed biopatterning methodology proved to be a simple and rapid approach to fabricate 3D cardiac models, especially for drug screening applications. Copyright 2023, Mary Ann Liebert, Inc., publishers.