Photothermal/Photodynamic Synergistic Antibacterial Hydrogel Dressing with pH/Glucose Dual Responsive Pirfenidone Release for Diabetic Foot Ulcers

Abstract

Diabetic foot ulcers (DFU) are notoriously challenging to heal due to severe infection, excessive inflammation, and difficulty in angiogenesis. In response to these problems, first, a pH/glucose dual-responsive hydrogel dressing (HPC) is constructed using dual dynamic crosslinking through Schiff base and phenylboronate ester between m-aminophenylboronic acid and adipic dihydrazide bifunctionalized hyaluronic acid (AHP) and oxidized chondroitin sulfate (OCS). Then, polydopamine-reduced graphene oxide compounded glycine-modified fullerene (GPC) with photothermal/photodynamic synergistic antibacterial properties and the drug pirfenidone (PFD) with pro-angiogenesis and suppress inflammatory are loaded into the above HPC hydrogel. Based on the response of Schiff base/phenylboronate ester to pH/glucose, the HPC/GPC/PFD (HPCG/PFD) hydrogel can accelerate the release of PFD, thereby improving excessive inflammation and angiogenesis in DFU. In addition, dual dynamic crosslinking provided the hydrogel with good on-demand removal and self-healing performance, while GPC brought good tissue adhesion, antioxidation, and electrical conductivity to the hydrogel. The rheology, morphology, mechanical properties, swelling, degradation, and biocompatibility of the hydrogel have been well verified. Finally, in the DFU model of rats, this hydrogel can promote wound repair by reducing infection and inflammation, accelerating wound closure, and enhancing epidermal regeneration, collagen deposition, and angiogenesis, showing promoting effect on diabetic wound healing.