Bioadaptive Porous 3D Scaffolds Comprising Cellulose and Chitosan Nanofibers Constructed by Pickering Emulsion Templating

Highly porous three-dimensional (3D) scaffolds can mimic the lobular structure of a human liver where hepatocytes are organized. However, 3D scaffolds with uniformly porous and oriented structures are challenging to fabricate without cross-linking agents. Herein, this work presents a Pickering emulsion-induced interface approach to construct aligned porous scaffolds for 3D cell cultures through the combined use of surface-carboxylated cellulose nanofibers and chitosan nanofibers as stabilizers, and freezing/lyophilization to remove the oil phase. The obtained Pickering emulsions exhibit long-term stability and their droplet sizes are tunable from 2.7 to 10.2 µm. Assembly at the oil–water interface can be modulated by controlling the NaCl dosage and oil phase proportion, resulting in porous foams with tunable porosity and versatile architectures as an in vitro alternative to the native liver microenvironment. The foams are noncytotoxic, confirmed using mouse fibroblast NIH/3T3 cells, and the cells grow both on the surface and in the internal structure of the foam. Notably, the 3D porous scaffolds are favorable microenvironments for the formation of human liver carcinoma HepG2 spheroidal cells, which exhibit liver-like activity. This strategy based on Pickering emulsion templating provides a new avenue for constructing bioadaptive 3D scaffolds, specifically all-biomass porous foams, for tissue engineering.