A multifunctional injectable, adhesive and self-healing carboxymethyl cellulose/alginate hydrogel reinforced with clove oil-caseinate nanoparticles for diabetic wound healing.

Abstract

Diabetic wound healing is frequently impaired by a persistently inflammatory wound microenvironment accompanied by impaired angiogenesis. Therefore, fabrication of advanced wound dressings to restore a favorable wound microenvironment is essential to accelerate the healing process. This study developed a carboxymethyl cellulose/sodium alginate (CMC/ALG) hydrogel reinforced with clove oil-loaded sodium caseinate nanoparticle (CO-CAS NPs) as a wound dressing with multifunctional properties for diabetic wound repair. Clove oil was extracted by hydro-distillation and characterized by GC-MS, revealing eugenol and β-caryophyllene as the principal constituents. The fabricated CO-CAS NPs exhibited EE of 82%, with surface charge of - 40.47 mV and hydrodynamic size of 330.4 nm. The CO-CAS NPs/CMC/ALG hydrogel exhibited superior swelling capacity, reduced degradation, sustained release, and favorable mechanical properties, including injectability, stretchability, moldability, and autonomous self-healing behavior. In vivo, CO-CAS NPs/CMC/ALG hydrogel significantly accelerated wound contraction, as wounds achieved complete closure by day 18, versus 91% in the blank hydrogel group. Histopathological analyses demonstrated that treatment with the CO-CAS NPs/CMC/ALG hydrogel promoted re-epithelialization, fibroblast proliferation, and collagen fiber organization. These findings were supported by significant suppression of IL-6 and oxidative stress markers, as well as significant upregulation of TGF-β and VEGF, reflecting improved tissue remodeling and angiogenesis. In vivo biocompatibility assessments confirmed excellent dermal safety with no irritation or histopathological changes. These findings collectively demonstrate that CO-CAS NPs/CMC/ALG hydrogel is an effective, biocompatible, and multifunctional dressing for diabetic skin wounds.