Sustainable Bioactive Hydrogels Engineered with Liquidambar orientalis Extracts: pH-Dependent Release Behavior and Wound Healing Potential

Abstract

Bioactive hydrogel films were developed by incorporating Liquidambar orientalis leaf extract (LOLE) and resin extract (LORE) into PVA/starch, PVA/chitosan, chitosan/gelatin, and chitosan matrices. HPLC-DAD identified myricetin as a major LOLE marker and trans-cinnamic acid as the predominant LORE compound, while SEM and FT-IR analyses supported extract incorporation and possible interactions within the hydrogel networks. The films exhibited polymer- and extract-dependent physicochemical behavior. LOLE-loaded chitosan films showed the highest swelling capacity (350%) and the highest in vitro mass loss after 14 days. Release studies demonstrated matrix-dependent and pH-dependent behavior within the tested pH range, with faster release generally observed at pH 5.5 than at pH 7.4; LOLE-loaded chitosan/gelatin films released 85.3% of the extract within 12 h at pH 5.5. LOLE-loaded hydrogels showed stronger antioxidant activity, whereas LORE-loaded films exhibited stronger antimicrobial performance against wound-associated microorganisms, reflecting their distinct phytochemical profiles. The extracts also showed antibiofilm, anti-quorum sensing, enzyme-inhibitory, and preliminary scratch wound closure activities, with no apparent cytotoxicity toward HEK-293T cells. LORE showed notable tyrosinase inhibition (IC50: 20.18 & micro;g/mL), suggesting pigmentation-related relevance. Overall, these findings support further investigation of L. orientalis-derived hydrogel films as sustainable bioactive wound dressing platforms, although mechanical, stability, and in vivo validations remain necessary.