Geometry-driven control of drug release kinetics in 3D printed chitosan scaffolds via an oxygen-self-supplying crosslinking strategy.

Chitosan-based hydrogels are attractive for drug delivery, yet their application in extrusion-based 3D printing is limited by slow gelation and insufficient shape stability. This work introduces a novel oxygen-self-supplying crosslinking mechanism using calcium peroxide (CaO2) to accelerate genipin-chitosan gelation. By actively generating oxygen, this strategy bypasses the rate-limiting step of ambient oxygen diffusion, enabling rapid, in situ activation of the nucleophilic addition between genipin and chitosan. This fundamental shift from passive diffusion to active, catalytic-driven reaction significantly accelerates gelation kinetics, allowing high-fidelity, layer-by-layer deposition without synthetic rheology modifiers. The printed scaffolds exhibited excellent shape fidelity, cytocompatibility, and retained antibacterial activity. Furthermore, by modulating scaffold architecture, specifically barrier thickness, infill density, and channel tortuosity, the release profiles of doxycycline and bovine serum albumin were precisely tuned, consistent with changes in diffusion path length and effective diffusivity. These results demonstrate that combining rapid in situ crosslinking with geometric design provides a practical, composition-independent approach for programming drug release kinetics in 3D printed chitosan hydrogels.