Biofunctional semi-interpenetrating gellan gum and silk sericin scaffolds encapsulated with betel leaf extract-β-Cyclodextrin inclusive complexes for wound healing.

Chronic wound treatment presents a significant challenge, requiring bioactive scaffolds that facilitate effective wound repair and promote skin regeneration with normal functionality. In this study, gellan gum (GG) networks were formed via physical crosslinking with divalent cations, while silk sericin (SS), as the linear phase, molecularly penetrated the pore volume of the GG network, resulting in the formation of semi-interpenetrating polymeric networks (semi-IPNs). The GG/SS scaffolds were enriched with betel leaf extract-encapsulated β-cyclodextrin complexes (B-ICs) to preserve the bioactive substance, improve the controlled release, and provide antibacterial, antioxidant and anti-inflammatory properties. Characterization through XRD, FTIR, and thermal analyses confirmed successful encapsulation and enhanced thermal stability, while SEM imaging revealed well-formed microporous structures. Mechanical testing showed that B-ICs significantly improved the compressive modulus and strength of the scaffolds. Additionally, the controlled release behavior of the B-ICs-GG/SS scaffolds, confirmed by the Korsmeyer-Peppas model, suggested anomalous transport as the release mechanism, aligning with the faster in vitro degradation rate. The scaffolds exhibited high phenolic content, resulting in excellent free radical scavenging activity to minimize oxidative stress and support an optimal wound healing environment. In vivo skin irritation test in rabbits confirmed that B-ICs-GG/SS scaffolds were non-irritant, suggesting the dermal safety and biocompatibility of the materials, a critical requirement for clinical translation. As a result, the B-ICs-GG/SS scaffolds would be a promising candidate for wound healing and tissue engineering applications.