A 3D bioprinted tumor model fabricated with gelatin/sodium alginate/decellularized extracellular matrix bioink

Abstract

Tissue-engineered scaffolds are more commonly used to construct three-dimension­al (3D) tumor models for in vitro studies when compared to the conventional two-dimensional (2D) cell culture because the microenvironments provided by the 3D tumor models closely resemble the in vivo system and could achieve higher success rate when the scaffolds are translated for use in pre-clinical animal model. Physical properties, heterogeneity, and cell behaviors of the model could be regulated to simulate different tumors by changing the components and concentrations of materials. In this study, a novel 3D breast tumor model was fabricated by bioprinting using a bioink that consists of porcine liver-derived decellularized extracellular matrix (dECM) with different concentrations of gelatin and sodium alginate. Primary cells were removed while extracellular matrix components of porcine liver were preserved. The rheolog­ical properties of biomimetic bioinks and the physical properties of hybrid scaffolds were investigated, and we found that the addition of gelatin increased hydrophilia and viscoelasticity, while the addition of alginate increased mechanical properties and porosity. The swelling ratio, compression modulus, and porosity could reach 835.43 ± 130.61%, 9.64 ± 0.41 kPa, and 76.62 ± 4.43%, respectively. L929 cells and the mouse breast tumor cells 4T1 were subsequently inoculated to evaluate biocompatibility of the scaffolds and to form the 3D models. The results showed that all scaffolds exhibited good biocompatibility, and the average diameter of tumor spheres could reach 148.52 ± 8.02 μm on 7 d. These findings suggest that the 3D breast tumor model could serve as an effective platform for anticancer drug screening and cancer research in vitro.