Lutein-loaded multifunctional hydrogel dressing based on carboxymethyl chitosan for chronic wound healing

Oxidative stress is a major contributor to the difficulties in chronic wound healing. Although antioxidant hydrogels have been developed, they are still insufficient for addressing the entire chronic wound healing process. In this study, a lutein-loaded multifunctional hydrogel dressing (Lutein/CMC/PVP/TA, Lutein/CPT) with synergistic antioxidation properties was developed by hydrogen bonding and electrostatic crosslinking of tannic acid (TA) with carboxymethyl chitosan (CMC) and polyvinylpyrrolidone (PVP). When loaded with 5 mg/mL of lutein, the 5Lutein/CPT hydrogel showed suitable swelling ratio, degradation rate, stability and biocompatibility. The hydrogel dressing demonstrates excellent self-healing behavior (≤20 s) and effectively extends the service life of the dressing. Importantly, this hydrogel displays pH-responsive drug release characteristics to meet the needs of the wound healing process. Specifically, under alkaline conditions (the initial stage of wound healing), TA and lutein are simultaneously released for synergistic antioxidant use in scavenging reactive oxygen species (ROS) and resolving inflammation. Under acidic conditions (late stage of wound healing), lutein is released to facilitate collagen formation. Additionally, the hydrogels demonstrated excellent antimicrobial (E. coli, S. aureus, and MRSA) activity and anti-biofilm ability. Animal experiments have shown that the 5Lutein/CPT hydrogel can promote wound closure, collagen fiber generation, angiogenesis and anti-inflammation. In conclusion, 5Lutein/CPT hydrogel dressings hold potential as candidate materials for promoting diabetic wound healing. Moreover, this study provides novel insights into the combined use of natural plant antioxidants in CMC-based hydrogel dressings to treat chronic wounds.