Customized Multilayered Tissue-on-a-Chip (MToC) to Simulate Bacillus Calmette-Guerin (BCG) Immunotherapy for Bladder Cancer Treatment

As an advanced cell culture platform, the organ-on-a-chip has been in the spotlight recently owing to its ability to maintain the physiological characteristics of cells in vitro. Therefore, several disease models have been developed using the organ-on-a-chip technology, and the organ specific three-dimensional (3D) structure and various mechanical/chemical stimuli built into the chip enable efficient development of drugs, medical devices, and biomaterials, as well as realization of patient-specific precise medicine. This study introduces a novel chip-based non-muscle invasive bladder cancer model, multilayered tissue-on-a-chip (MToC), which was created using 3D bio-printing technology, micro-milling, and soft lithography based polydimethylsiloxane (PDMS) casting. All types of cells, T24, MRC-5, and HUVEC, were successfully co-cultured in the MToC. Using computational fluid dynamics (CFD), the flow phenomena occurring in MToC were analyzed. Further, we attempted Bacillus Calmette-Guerin (BCG)-induced migration of THP-1, and the viability reduction of bladder cancer cells and the THP-1 migration were observed. Although follow-up studies are needed to precisely mimic the immune response, this partial phenomenon of the immune response suggests the potential of this device as a surrogate experimental tool for BCG immunotherapy in future.

Automated summary

The organ-on-a-chip technology, an advanced cell culture platform, has garnered attention recently for its ability to maintain the physiological characteristics of cells. This technology enables efficient development of drugs, medical devices, and biomaterials, as well as realization of patient-specific precise medicine through organ-specific 3D structures and various mechanical/chemical stimuli built into the chip.