3D bioprinting of a perfusable tumor microenvironment model to investigate perfusion and chemotherapeutic responses in ovarian cancer cells

Understanding the role of perfusion and chemotherapeutic response in solid tumors require advanced in vitro models that closely recapitulate the tumor microenvironment. Addressing this need, we developed a perfusable three-dimensional (3D) GelMA-gelatin-based tumor model embedded with a hollow microchannel to investigate spatial variations in SKOV3 ovarian cancer cell behavior and their response to carboplatin. This study aims to overcome the limitations of conventional 2D and non-perfused 3D cultures by introducing controlled perfusion and directional drug delivery, thereby providing a more physiologically relevant platform for cancer research and drug testing. Using extrusion- and inkjet-based bioprinting, SKOV3 cells were cultured within the GelMA-gelatin matrix and exposed to continuous medium flow. We observed a strong dependence of cell behavior on distance from the perfusion channel. Cells closer to the channel (0–300 µm) showed increased elongation (aspect ratio: 3.5), faster migration (28.98 µm/day), higher viability (96%), and elevated proliferation (index: 3.8), which progressively declined with increasing distance. Upon carboplatin exposure (0–50 µM), SKOV3 cells exhibited dose-dependent reductions in viability, proliferation, migration, and elongation, with aspect ratio dropping to 1.17 and viability to 5% at 50 µM. Matrix degradation analysis revealed increased pore enlargement under perfusion (from 87 µm to 190 µm), suggesting higher MMP activity. This perfused 3D model enables precise evaluation of chemotherapeutic efficacy and tumor cell heterogeneity, offering a powerful tool for preclinical drug screening, tumor biology research, and future integration of vascular and immune components.