Feasibility of a Photocurable 3D Bioprinted Primary Colorectal Cancer Model for In Vitro Drug Evaluation

Objective: To establish and validate the feasibility of a photocurable 3D bioprinted in vitro model using primary colorectal cancer (CRC) cells, aiming to better recapitulate tumor architecture and biological heterogeneity compared with conventional two-dimensional cultures.

Methods: Primary tumor tissues were obtained from patients with colorectal cancer and enzymatically dissociated into single-cell suspensions. A photocurable bioink composed of gelatin methacrylate (GelMA), hyaluronic acid methacrylate (HAMA), and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) was prepared and mixed with primary CRC cells. Three-dimensional tumor constructs were generated using a high-throughput light-based 3D bioprinting system and cultured under standard conditions. Model stability, morphology, and cell viability were monitored microscopically. Reproducibility was evaluated by repeated bioprinting and parallel drug exposure experiments.

Results: Photocurable 3D bioprinting successfully generated structurally stable and reproducible primary CRC constructs across multiple patient-derived samples. Tumor spheroids maintained compact architecture and sustained viability during long-term culture. The model demonstrated high experimental consistency, with low inter-batch variability and good repeatability in drug response assays. Compared with 2D cultures, the 3D bioprinted model exhibited increased resistance to chemotherapy, suggesting improved simulation of the in vivo tumor microenvironment.

Conclusion: Photocurable 3D bioprinting is a feasible and reliable approach for constructing primary colorectal cancer models in vitro. This platform provides a biologically relevant and reproducible system that better reflects tumor heterogeneity and drug response characteristics, supporting its application in translational research and precision oncology.