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

Abstract 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.