Massive fabrication of functional hepatic cancer spheroids by micropatterned GelMA hydrogel chip for drug screening.

Since hepatic cancer incidence and mortality continue to grow worldwide, it is necessary to develop the biomimetic tumor models for drug development and tumor therapeutics. Cellular spheroids as an excellent simple 3D model can bridge the gap between 2D cell culture and live tissue. In this study, we proposed a biological methacrylated gelatin (GelMA) hydrogel-based microplatform for the massive generation of hepatocellular spheroids and downstream investigation of drug resistance. Micropatterned GelMA hydrogel microwell chip (GHM-chip) with tunable array was easily achieved in standard 24-culture well plates through the micro-molding fabrication strategy. The fabricated GHM-chip induced multicellular self-assembly behavior within the defined topography and further formed spheroidal structure. By regulating cell seeding density and designing microwell size, uniform hepatic cancer spheroids with tunable diameters were obtained in a simplicity, stability and controllable manner. In addition, the screening chemotherapy study of anti-cancer drug was completed through non-destructive recovery of spheroids from the GHM-chip. Beyond that, the recovered functional spheroids have potential application value in various biomedical fields such as tumor biology, pharmacology, and tissue microengineering. Finally, the proposed GHM-chip incorporated into standard cell culture plates with easy to manufacture and operate properties, may be an efficient culture microplatform for cancer research applications.