Self‐assembly of multi‐scale anisotropic hydrogels through interfacial polyionic complexation

: Polysaccharides are explored for various tissue engineering applications due to their inherent cytocompatibility and ability to form bulk hydrogels. However, bulk hydrogels offer poor control over their microarchitecture and multi-scale hierarchy, parameters important to recreate extracellular matrix-mimetic microenvironment. Here, we developed a versatile platform technology to self-assemble oppositely charged polysaccharides into multi-scale fibrous hydrogels with controlled anisotropic microarchitecture. We employed polyionic complexation through microfluidic flow of positively charged polysaccharide, chitosan, along with one of the three negatively charged polysaccharides: alginate, gellan gum, and kappa carrageenan. These hydrogels were composed of micro-scale fibers, which in turn were made of sub-micron fibrils confirming multi-scale hierarchy. Fibrous hydrogels showed strong tensile mechanical properties, which were further modulated by encapsulation of shape-specific antioxidant cerium oxide nanoparticles. Specifically, hydrogels with chitosan and gellan gum showed more than eight times higher tensile strength compared to the other two pairs. Incorporation of sphere-shaped cerium oxide nanoparticles in chitosan and gellan gum further reinforced the fibrous hydrogels and increased tensile strength by 40%. Altogether, our automated hydrogel fabrication platform allows fabrication of bioinspired biomaterials with scope for one-step encapsulation of small molecules and nanoparticles without chemical modification or use of chemical crosslinkers. This article is protected by copyright. All rights reserved.