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, we propose a simple strategy to engineer biomimetic fiber bundles that replicate the self-assembly and hierarchy of natural collagen fibers. The electrostatic interaction of methacrylated gellan gum (MeGG) with a countercharged chitosan (CHT) polymer led to the complexation of the polyelectrolytes. When directed through a polydimethylsiloxane (PDMS) channel, the polyelectrolytes formed a hierarchical fibrous hydrogel demonstrating nano-scale periodic light/dark bands similar to D-periodic bands in native collagen and aligned parallel fibrils at micro-scale. Importantly, collagen-mimicking hydrogel fibers exhibited robust mechanical properties (MPa scale) at a single fiber bundle level and enabled encapsulation of cells inside the fibers under cell-friendly mild conditions. Presence of carboxyl- (in gellan gum) or amino- (in chitosan) functionalities further enabled controlled peptide functionalization such as 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.