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

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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.