Baicalein-loaded chitosan sponges for applications in regenerative dentistry

This study investigated the development and characterization of baicalein-loaded chitosan sponges for potential use in regenerative dentistry. Using a 3 × 3 factorial design, nine formulations were prepared by varying chitosan concentration (1-3%) and molecular weight (low, medium, and high). The sponges were evaluated for physicochemical and mechanical properties, drug release behavior, mucoadhesion, antioxidant, anti-inflammatory, antimicrobial activity, and biological compatibility. Scanning electron microscopy confirmed the formation of porous, lyophilized structures, with morphology dependent on chitosan concentration and molecular weight. Mechanical properties, including resilience and Young's modulus, were tunable through formulation parameters. Baicalein release followed Korsmeyer-Peppas kinetics and was slower in denser matrices. Mucoadhesion increased with higher chitosan concentration and was inversely correlated with drug release rate. Biological assays showed that antioxidant activity was enhanced at lower chitosan concentrations and higher molecular weight, whereas anti-inflammatory effects were associated with faster drug release and increased mucoadhesion. Studies with human dental pulp stem cells confirmed good cytocompatibility, normal cell morphology, and sustained metabolic activity. Wound healing assays demonstrated that baicalein-loaded sponges significantly improved cell migration and wound closure compared to free baicalein. Statistical modelling identified two optimal formulations: formulation 3 (BAI1_CS3_LMW) as a fast-acting system and formulation 7 (BAI1_CS1_HMW) as a sustained-release system. These outcomes reflected clear structure-property relationships governed by chitosan molecular weight and concentration. The sponges also showed good blood and i-PRF absorption and antimicrobial activity against oral pathogens. Baicalein-loaded chitosan sponges exhibit tunable physicochemical and biological properties, representing a promising platform for localized oral wound healing and regenerative dental therapies.