Non-Thermal Plasma-Induced Selective Glycosidic Cleavage in Chitosan Produces Multifunctional Antibacterial Wound Care Biomaterials

Multifunctional biomaterials capable of simultaneously controlling bleeding, preventing infection, and promoting tissue regeneration are a critical need in contemporary healthcare. Herein, a sustainable and additive-free strategy for the molecular engineering of chitosan using non-thermal plasma (NTP) is presented. A custom-engineered underwater NTP bubbling system is employed to effectively cleave the β-(1→4)-glycosidic linkages between D-glucosamine and N-acetyl-D-glucosamine units under ambient conditions. The process yielded a chitosan material with markedly reduced molecular weight. Notably, in the plasma environment, hydroxyl radical-induced depolymerization reached its highest efficiency under UV-assisted conditions, indicating a synergistic effect between reactive species and plasma-emitted UV radiation, as supported by quantum chemical modeling. Mechanistic insights obtained via omics-level profiling and synchrotron ATR-FTIR macro spectroscopy revealed a multi-targeted antimicrobial action. In vitro and in vivo wound models validated that the NTP-modified chitosan promotes accelerated re-epithelialization, downregulates inflammation, and enhances tissue regeneration compared to native chitosan. This work establishes a novel, highly effective, and sustainable NTP technology for engineering bioactive biopolymers with potential for advancing the next generation of multifunctional regenerative biomaterials.