In vitro cell study has been widely used as the smallest structural and functional unit of living organisms in bio-field industry to develop a variety of biomaterial and drug products. Also, most of cell studies has been carried out as in vitro 2D assay on a plastic well-plate due to simple and low-cost advantages. However, as an in vitro test model to represent the human organ and tissue systems, 2D assay has critical limitations such as environmental difference from the natural 3D organ system, and the restricted interactions between cellular and extracellular matrix. These mismatches could lead cost waste in the bio-field industry because in vitro cell study could not play the subjected role to support much higher-cost in vivo animal test. In this light, the direction of cell test platform needs to head toward increasing in vitro data reliability, while it could be commercially used in bio-field company.
Herein, using two types of hepatocellular carcinoma cells (HepG2 or Hep3B), we fabricate 'cell laden microgel' as a size and component tunable 3D cell culture platform through microfluidics technology, which can generate cell laden microgels in a monodisperse and high-throughput manner. With this microgel model, we adjust various gel-stiffness and hyaluronic acid (HA) component, which composes liver extracellular matrix as bioactive glycosaminoglycans, to mimic the natural human liver tissue modulus and composition, as well as to compare 3D-cultured cell behaviors within various kinds of microgel so that we can analyze each variable effect on the cell fate up to 21 days, not affected by non-uniform diffusion issue. Lastly, we utilize this cell laden microgel as a high-throughput drug screening platform to investigate chemotherapeutic effect since microgel is a constant drug diffusion platform due to micro-sized hydrogel layer.