Natural polymer hydrogel based 3D printed bioreactor testing platform for cancer cell culture

Abstract

Although two-dimensional cell cultures provide a time- and cost-effective method for testing drugs at the preclinical level, they do not capture the three-dimensional cellular interactions or tumor penetration that must occur in vivo. Therefore, these drugs often fail as they transition from two-dimensional culture models to more complex ones, including animal models or even human clinical trials. The goal of this research was to develop a three-dimensional bioprinted pancreatic cancer drug testing platform that could increase the effectiveness of drug testing during the early preclinical stages. Specifically, different natural polymer hydrogel formulations of cellulose, alginate, and gelatin were tested to find the optimal printability and cell viability. It was determined that a cellulose nanocrystal and alginate hydrogel provided the best printability because of its superior shear thinning properties. In addition, BxPC-3 cells, that were printed and then cultured within this hydrogel for four days, exhibited a range of cell viability between 80 % and 60 %. To simulate vasculature around the bioprinted cultures, a spinning bioreactor was manufactured; however, it disturbed the cells, leading to a decrease in cell viability compared to stagnant cultures. Overall, the platform demonstrated good printability and cell viability for future use in pancreatic cancer drug testing.