Evaluation of wound regeneration potential of nano-phytoextracts loaded carboxymethyl chitosan scaffolds for diabetic foot ulcer

Diabetic foot ulcer (DFU) is a common complication of diabetes mellitus affecting 15-25% of diabetic patients causing chronic pain, morbidity, amputation, economic burden, and, in some cases, mortality. Current treatments face significant challenges including poor antimicrobial efficacy, multidrug resistance and high costs. This study aimed to develop a novel carboxymethyl chitosan (CMCh) based scaffold enriched with green tea extract (GTE) and Acacia catechu extract (ACE), intending to leverage their complimentary antimicrobial, antioxidant and regenerative properties for wound healing beyond individual component effects. The scaffolds were fabricated via freeze‒drying with vanillin crosslinking. Comprehensive characterization using various spectroscopy and microscopy confirmed the successful incorporation of the phytoextracts with retained functional groups and thermal stability. The synthesized CMCh + GTE + ACE scaffolds had a mean pore size of 131 ± 43 μm with 400% absorption capacity. Antibacterial assay indicated that they exhibited meaningful broad-spectrum activity with a 17 mm zone of inhibition against bacterial strains commonly found in DFU. In vivo studies revealed that the developed scaffolds were nontoxic and nonirritant and demonstrated enhanced wound healing potential, with the CMCh + GTE + ACE scaffold resulting in 99% wound closure in comparison with 70% in the untreated control group. Furthermore, histopathology studies revealed enhanced keratinocyte proliferation, ECM deposition, epithelialization and vascularization. Thus, the results indicated that nanoscaffolds show potential for clinical application as an innovative plant based bioactive treatment for DFU management and necessitates further long-term studies for optimization and clinical translation.