Enhanced diabetic foot ulcer treatment with a chitosan-based thermosensitive hydrogel loaded self-assembled multi-functional nanoparticles for antibacterial and angiogenic effects

Abstract

Inhibiting bacterial growth and promoting angiogenesis are essential for enhancing wound healing in diabetic patients. Excessive oxidative stress at the wound site can also lead to an accumulation of reactive oxygen species. To address these challenges, a smart thermosensitive hydrogel loaded with therapeutic agents was developed. This formulation features self-assembled nanoparticles named CIZ, consisting of chlorogenic acid (CA), indocyanine green (ICG), and zinc ions (Zn²⁺). These nanoparticles are loaded into a chitosan-β-glycerophosphate hydrogel, named CIZ@G, which enables rapid gel formation under photothermal effects. The hydrogel demonstrates good biocompatibility and effectively releases drugs into diabetic foot ulcers (DFU) wound. Benefiting from the dual actions of CA and zinc ions, the hydrogel exhibits potent antioxidative and anti-inflammatory effects, enhances the expression of vascular endothelial growth factor (VEGF) and Platelet endothelial cell adhesion molecule-1 (CD31), and promotes angiogenesis. Both in vitro and in vivo experiments confirm that CIZ@G can effectively inhibit the growth of Staphylococcus aureus post-laser irradiation and accelerate wound remodeling within 14 days. This approach offers a new strategy for the treatment of diabetic foot ulcers (DFU), potentially transforming patient care in this challenging clinical area.