Construction of 3D bioprinted colorectal cancer models and evaluation of their efficacy and drug sensitivity.

Currently, preclinical research on colorectal cancer (CRC) lacks effective tumor models. In recent years, 3D bioprinted models have shown great potential in tumor model construction.

This study used 3D bioprinting technology to establish a CRC extracellular matrix (ECM) model. Gradient concentrations of laminin/entactin complex combined with photocurable gelatin methacrylate (GelMA) hydrogel were used to prepare 3D bioprinting bioinks with biomimetic ECM properties. Biocompatibility was assessed by calcein-AM and propidium iodide staining. Proliferation was evaluated using the CellTiter-Glo® Luminescent Cell Viability Assay Kit in SW620 cells and primary CRC cells.

A "sandwich structure" model with inner and outer layers of GelMA or GelMA + LE2 was constructed to observe cell invasion. Mechanical properties of GelMA + LE2 were characterized. Total RNA was extracted from cells in 3D bioprinted models constructed with GelMA and GelMA + LE2 for transcriptome sequencing. Finally, chemotherapeutic drug tests were performed on the 3D bioprinted models.

A 3D bioprinted CRC organoid model based on GelMA + LE2 was successfully established. This model exhibited good biocompatibility and the ability to promote tumor cell proliferation and invasion. These characteristics were independent of the model's mechanical properties. Instead, they originated from LE2 activating the ErbB/Wnt signaling pathway and gap junction-mediated intercellular communication.

Additionally, a significant correlation was observed between the clinical treatment outcomes of CRC patients and the drug test results of the 3D bioprinted models. The 3D bioprinted CRC organoid constructed in this study provides a biomimetic and high-throughput research platform for precision medicine.