Biopatterning of 3D Cellular Model by Contactless Magnetic Manipulation for Cardiotoxicity Screening.

Patterning cells to create 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 bio-ink that consists alginate, cells, and magnetic nanoparticles (MNPs). Plackett-Burman and Box-Behnken experimental design models were used to optimize bio-ink 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, 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 2D cell culture. Hereby, developed biopatterning methodology proved to be a simple and rapid approach to fabricate 3D cardiac models, especially for drug screening applications.