Oxidized regenerated cellulose-based supermolecular hydrogel for controlled drug release: Integrating cyclodextrin-mediated hydrophobic drug distribution, wound-specific degradation, and multifunctional therapeutic effects.

Multifunctional wound dressings with rapid hemostasis, antimicrobial and anti-inflammatory properties, healing promotion, pain relief, and controlled degradation hold significant clinical potential. Herein, we developed a novel hydrogel system by functionalizing oxidized regenerated cellulose (ORC) with l-lysine (L-Lys) through dynamic Schiff base linkages. This strategy endowed the hydrogel with natural antimicrobial activity and enabled controlled release of L-Lys for tissue regeneration. Moreover, hydrophobic ibuprofen (IBU) was encapsulated using hydroxypropyl-β-cyclodextrin (HP-β-CD), effectively improving its solubility, dispersion, and delivery within the hydrophilic hydrogel matrix. This supramolecular host-guest approach solved the common challenge of incorporating hydrophobic drugs into aqueous systems. The hydrogel's structure and morphology were systematically characterized, confirming successful fabrication. Antimicrobial assays revealed strong inhibition against E. coli and S. aureus, with inhibition zones of 25.3 ± 0.12 mm and 34.4 ± 0.11 mm, respectively. Degradation studies showed complete disintegration within 60 h, with easy removal using saline. In vivo wound healing experiments demonstrated 98.5 % wound closure within 13 days. Histological analysis confirmed that the combined release of L-Lys and IBU significantly promoted tissue regeneration. This work introduces an innovative platform that leverages dynamic covalent chemistry and cyclodextrin-based drug delivery for next-generation wound dressings with enhanced therapeutic performance.