Abstract

Developing Bioink Formulations that Promote Multicellular Tumor Organoid Growth

Joseph Kinsella, Assistant Professor of Bioengineering, McGill University

The cellular, biochemical, and biophysical heterogeneity of native tissue microenvironments are not recapitulated by growing immortalized cell lines using conventional 2D cell culture. These challenges can be overcome using bioprinting techniques to build heterogeneous 3D tissue models whereby, different types of cells are embedded. Alginate and gelatin are two of the most common biomaterials employed in bioprinting due to their biocompatibility, biomimicry, and mechanical properties. By combining the two polymers we demonstrate a bioprintable composite hydrogel with likenesses to the microscopic architecture of native tissue stroma. The printability of the composite hydrogels are evaluated mechanically to acquire the optimal extrusion bioprinting timescale post-gelation. Breast cancer cells and fibroblasts embedded into the hydrogels can be printed to form a 3D model mimicking the in vivo tumor microenvironment. The bioprinted heterogeneous model achieves high viability for long-duration cell culture (>30 days) and promotes the self-assembly of the breast cancer cells into multicellular tumor spheroids (MCTSs). We observed migration of the cancer associated fibroblast cells (CAFs) with the MCTSs in this model. Using bioprinted cell culture platforms as co-culture systems we are able to develop a unique tool to study the dependence of tumorigenesis on the stroma composition. The materials developed are a continuous effort towards a physiologically relevant “universal” bioink that can be tuned to have specific initial mechanical and biochemical properties for different tissue architectures.