Self‐Assembled Hydrogel Fiber Bundles from Oppositely Charged Polyelectrolytes Mimic Micro‐/Nanoscale Hierarchy of Collagen

Fiber bundles are present in many tissues throughout the body. In most cases, collagen subunits spontaneously self‐assemble into a fibrilar structure that provides ductility to bone and constitutes the basis of muscle contraction. Translating these natural architectural features into a biomimetic scaffold still remains a great challenge. Here, a simple strategy is proposed to engineer biomimetic fiber bundles that replicate the self‐assembly and hierarchy of natural collagen fibers. The electrostatic interaction of methacrylated gellan gum with a countercharged chitosan polymer leads to the complexation of the polyelectrolytes. When directed through a polydimethylsiloxane channel, the polyelectrolytes form a hierarchical fibrous hydrogel demonstrating nanoscale periodic light/dark bands similar to D‐periodic bands in native collagen and align parallel fibrils at microscale. Importantly, collagen‐mimicking hydrogel fibers exhibit robust mechanical properties (MPa scale) at a single fiber bundle level and enable encapsulation of cells inside the fibers under cell‐friendly mild conditions. Presence of carboxyl‐ (in gellan gum) or amino‐ (in chitosan) functionalities further enables controlled peptide functionalization such as Arginylglycylaspartic acid (RGD) for biochemical mimicry (cell adhesion sites) of native collagen. This biomimetic‐aligned fibrous hydrogel system can potentially be used as a scaffold for tissue engineering as well as a drug/gene delivery vehicle.