Development of a 3D-bioprinted tumour-on-chip with tunable hydrogel properties for monitoring colorectal cancer cell migration and invasion

Abstract

Understanding the mechanisms governing cancer cell migration is essential for elucidating the early events of colorectal cancer metastasis. Here, we report the development of a light-tunable three-dimensional (3D) bioprinted tumour-on-chip platform for monitoring the migration of colorectal cancer cells under biomimetic microenvironmental conditions. The platform integrates digital light processing (DLP)-based 3D bioprinting with microfluidic technology to recreate structural and mechanical features of the colorectal tumour microenvironment. A hybrid bioink composed of gelatin methacryloyl (GelMA), Matrigel, and type I collagen was formulated to balance DLP printability with biologically relevant extracellular matrix components. Multi-compartment tumour constructs were fabricated with HCT116 colorectal cancer cells spatially confined within a central tumour region, while human umbilical vein endothelial cells (HUVECs) were incorporated into surrounding compartments under co-culture conditions. By modulating the projected light intensity, constructs with tunable properties were generated to investigate the influence of matrix mechanics and transport on cancer cell behaviour. Comparison of Day 1 and Day 4 fluorescence images revealed outward redistribution of the HCT116-positive signal beyond the initially printed tumour core, consistent with colorectal cancer cell migration. The extent of this redistribution was influenced by the light-defined matrix properties and the presence of the neighbouring HUVEC-containing co-culture compartment, highlighting the combined role of physicochemical and cellular cues in regulating tumour cell behaviour. The system also establishes a foundation for future studies of tumour invasion, endothelial barrier interactions, and therapeutic screening under controlled perfusion conditions, supporting the advancement of personalized cancer models and anti-metastatic drug development.