Quaternized chitosan nanoparticles encapsulating EGCG-Zn complex: A novel approach to accelerate diabetic wound healing in mice

Diabetic wounds are a frequent and serious complication of diabetes, and their treatment remains a critical clinical challenge. In this study, we developed an innovative ternary nanocomposite system by first chelating epigallocatechin gallate (EGCG) with Zn 2+ to form a complex, which was then incorporated into quaternized chitosan (QCS). The resulting EGCG-Zn-QCS nanoparticles demonstrated excellent stability, dispersibility, and sustained release of EGCG. In vitro , they scavenged ABTS and DPPH radicals, reduced lipopolysaccharide (LPS)-induced IL-6 and TNF-α secretion in RAW264.7 macrophages, and inhibited Staphylococcus aureus growth and biofilm formation. In diabetic mice with full-thickness wounds, EGCG-Zn-QCS nanoparticles significantly enhanced healing compared to EGCG or EGCG-Zn. It promoted macrophage polarization from M1 to M2 phenotype, decreased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), increased anti-inflammatory IL-10, enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) levels. It also upregulated TGF-β, VEGF, EGF, HIF-α, α-SMA, and CD31, promoting cell proliferation and angiogenesis. The nanoparticles showed no hemolysis or toxicity, with normal serum markers (aspartate and alanine aminotransferases, urea, creatinine) and no organ pathology, indicating strong biocompatibility and safety. Overall, EGCG-Zn-QCS nanoparticles offer a promising strategy for diabetic wound healing.