Background

Impaired wound healing in diabetic patients remains a major clinical challenge due to oxidative stress, chronic inflammation, and compromised tissue regeneration.

Objective

This study aimed to develop and evaluate a novel nanocomposite hydrogel system incorporating lipoic acid and melatonin to enhance diabetic wound healing.

Methods

Chitosan nanoparticles co-loaded with lipoic acid and melatonin (LAMELCNPs) were embedded within a calcium alginate hydrogel to form a bioactive wound dressing (LAMELCNPHYD). The system was characterized in terms of its microstructure, swelling behavior, drug release profile, cytocompatibility, antioxidant capacity, anti-inflammatory activity, and hemocompatibility. In vivo wound healing efficacy was assessed using a streptozotocin-induced diabetic rat model.

Results

Scanning electron microscopy (SEM) confirmed the porous hydrogel structure. LAMELCNPHYD showed sustained drug release, excellent cytocompatibility, and enhanced antioxidant and anti-inflammatory activity. In vivo, LAMELCNPHYD significantly improved wound closure, collagen deposition, epithelial regeneration, and modulation of inflammatory markers (reduced interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9); increased transforming growth factor-beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF)).

Conclusion

The LAMELCNPHYD hydrogel demonstrated potent wound healing efficacy through combined antioxidative, anti-inflammatory, and regenerative mechanisms, offering a promising therapeutic strategy for diabetic wound management.