Engineered novel dually cross-linked hydrogel system embedded with Apigenin–cyclodextrin complex for surgical wound healing

Surgical wounds present a critical clinical challenge often requiring advanced therapeutic strategies to accelerate healing and enhance tissue regeneration. Herein, we engineered novel dually cross-linked hydrogel system incorporating an Apigenin-β-cyclodextrin (API–βCD) inclusion complex for enhanced wound therapy. First, the API–βCD inclusion complex was prepared and characterized comprehensively through nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), scanning electron microscopy (SEM), molecular docking and phase solubility studies. Then, dually cross-linked hydrogel matrix embedded with the API–βCD complex was synthesized and assessed for comprehensive structural, mechanical and physiochemical properties. In vitro release, ex vivo permeation, cell viability, antibacterial activity, wound closure and anti-inflammatory cells analyses of the API–βCD hydrogel were performed. Results confirmed the formation of successful inclusion complex. Phase solubility study demonstrated 66.8 ~ fold increase in the aqueous solubility of API. FTIR analysis confirmed successful crosslinking within the hydrogel matrix. Moreover, API–βCD hydrogel exhibited enhanced mechanical properties, porous architecture and optimal swelling and degradation behaviors. In vitro and ex vivo studies demonstrated sustained release, minimal permeation and enhanced disposition (57%) of API in skin layers, higher cell viability, and augmented antibacterial potential. Additionally, API–βCD hydrogel demonstrated significantly accelerated wound healing with 97% wound closure and noticeable downregulation of inflammatory parameters, such as TNF-α and IL-1β. These results concluded that API–βCD hydrogel may improve the solubility, dissolution of API and holds promising potential for regenerative wound management.