3D bioprinting of hepatoma cells and application with microfluidics for pharmacodynamic test of Metuzumab

Abstract

Constructing in vitro drug models with a higher degree of bionics is considered to be an important approach to improve the effectiveness of existing drug screening models. 3D printing, co-culture and microfluidics are important methods that commonly used. This study combined the advantages of the three methods. A 3D co-culture microfluidic model with controllable hepatoma cluster size was constructed, and applied to pharmacodynamic tests of a new anti-CD147 monoclonal antibody, Metuzumab. In the phase of cell preparation, hepatoma cells in the new model were found to proliferate faster than common in vitro 3D models fabricated by cell printing only. The hepatoma cells were also found less affected by the increase of drug dosage in migration performance, proliferation performance and protein expression level in the new model compared with 2D models. These results are in line with those obtained from animal experiments and clinical trials of similar anti-CD147 antibody drugs. In view of the special mechanism of antibody drugs, a modified model was built by adding peripheral blood mononuclear cells into the new model as effector cells, porting traditional antibody-dependent cell-mediated cytotoxicity (ADCC) test to a co-culture 3D microfluidic microenvironment. The results showed that ADCC exhibited higher effectiveness in the microfluidic model than in 3D printing models under the same dose of drug treatment. The new model was proved constructive and it provided a valuable reference for complex in vitro hepatoma model studies and antibody drug screening researches.