Hierarchically Inverse Opal Porous Scaffolds from Droplet Microfluidics for Biomimetic 3D Cell Co-Culture

With the advantages of better mimicking the specificity of natural tissues, three-dimensional (3D) cell culture plays a major role in drug development, toxicity testing, and tissue engineering. However, existing scaffolds or microcarriers for 3D cell culture are often limited in size and show suboptimal performance in simulating the vascular complexes of living organisms. Therefore, we present a novel hierarchically inverse opal porous scaffold made via a simple microfluidic approach for promoting 3D cell co-culture techniques. The designed scaffold is constructed using a combined concept involving an emulsion droplet template and inert polymer polymerization. This work demonstrates that the resultant scaffolds ensure a sufficient supply of nutrients during cell culture, so as to achieve large-volume cell culture. In addition, by serially planting different cells in the scaffold, a 3D co-culture system of endothelial-cell-encapsulated hepatocytes can be developed for constructing certain functional tissues. It is also demonstrated that the use of the proposed scaffold for a co-culture system helps hepatocytes to maintain specific in vivo functions. These hierarchically inverse opal scaffolds lay the foundation for 3D cell culture and even the construction of biomimetic tissues.