Responsive Inverse Opal Scaffolds with Biomimetic Enrichment Capability for Cell Culture

Three-dimensional (3D) porous scaffolds have a demonstrated value for tissue engineering and regenerative medicine. Inspired by the predation processes of marine predators in nature, we present new photocontrolled shrinkable inverse opal graphene oxide (GO) hydrogel scaffolds for cell enrichment and 3D culture. The scaffolds with adjustable pore sizes and morphologies were created using a GO and N-isopropylacrylamide dispersed solution as a continuous phase of microfluidic emulsions for polymerizing and replicating. Because of the interconnected porous structures and the remotely controllable volume responsiveness of the scaffolds, the suspended cells could be enriched into the inner spaces of the scaffolds through predator-like swallowing and discharging processes. Hepatocyte cells concentrated in the scaffold pores could form denser 3D spheroids more quickly via the controlled compression force caused by the shrinking of the dynamic scaffolds. More importantly, with a program of scaffold enrichment with different cells, an unprecedented 3D multilayer coculture system of endothelial-cell-encapsulated hepatocytes and fibroblasts could be generated for applications such as liver-on-a-chip and bioartificial liver. It was demonstrated that the resultant multicellular system offered significant improvements in hepatic functions, such as albumin secretion, urea synthesis, and cytochrome P450 expression. These features of our scaffolds make them highly promising for the biomimetic construction of various physiological and pathophysiological 3D tissue models, which could be used for understanding tissue level biology and in vitro drug testing applications.