Advanced ADA-GEL bioink for bioprinted artificial cancer models

Abstract

One of the main problems encountered in cancer pathologies is the lack of proper in vitro systems resembling the architecture of tumoral tissues. Since 2D surfaces do not represent the morpho-mechanical characteristics of malignant milieus, 3D systems are rapidly gaining interest in the field of Biomaterials for Cancer Research.In this work, we used a new kind of hydrogel-based scaffold constituted by crosslinked alginate di-aldehyde (ADA) and gelatin (GEL) to mimic the tumoral milieu in vitro by biofabrication. For this purpose, flat 2D films and 3D bioprinted scaffolds were crosslinked with solutions of calcium, barium, and combinations of the two. These structures were analyzed in terms of their chemical and mechanical properties, as well as their biological compatibility in the presence of the tumoral cell line HCT116 (colorectal cancer).Our results indicate that ADA-GEL, crosslinked with these divalent ions, can perform effectively as an artificial cancer model, matching the mechanical properties of colorectal tumors, as well as enabling cell growth in confinement. Furthermore, the use of different combinations of divalent ions allowed the tailoring of the mechanical properties of the material.The cell-loaded ADA-GEL constructs are not significantly affected by the type of crosslinking ion. The best outcome was achieved when 3D printed structures were produced with an ADA concentration of 2.5 (w/v)% and crosslinked with barium, showing remarkable results in terms of printability and mechanical properties. With this composition and barium as the crosslinking ion, a stiffness of 44.97 kPa was achieved, compared with calcium crosslinked samples, where it was only possible to achieve an elastic modulus of 21.55 kPa.This work demonstrates that ADA-GEL-based matrices are a very interesting option to perform as tumor-like scaffolds, which could be used to improve current methods of drug testing as well as for personalized medicine.