Chondroitin Sulfate-Based MPDA@MnO₂ Nanocomposite Hydrogels: A Smart Drug Delivery System with pH/ROS Responsiveness...

Chronic wounds, particularly those complicated by infection, present significant challenges in clinical management. The microenvironment of these wounds is typically characterized by the accumulation of reactive oxygen species (ROS) and abnormal local pH levels, both of which impede the healing process. Baicalin (BA), a natural flavonoid, exhibits anti-inflammatory activity, ROS-scavenging capability, and pro-healing effects. In this study, hydrogels were synthesized through photoinitiated radical polymerization of methacrylic anhydride (MAA) and dopamine (DA)-modified chondroitin sulfate (ChSMA-DA), grafting degrees of MA and DA were 58%, 23%, MPDA@MnO₂ nanoparticles (NPs), and methacrylated gelatin (GelMA). The gelation time, microtopography, swelling behavior, and water retention of the hydrogels were investigated, along with their degradation, rheological properties, and photothermal effects. The results indicate that swelling ratio (SR) and water retention (WR) of optimal HG-MPDA@MnO₂-M sample were 5.7, 82.42%, exhibited responsive behavior upon weakly acidic environment with pH 6.5 and elevated ROS levels, and exhibited a stable photothermal effect (photothermal conversion efficiency was 22.7%) under 808 nm near-infrared (NIR) light. Following the incorporation of the drug model BA, the cumulative release percentage over 24 h under the combined stimulation of pH 6.5, 1 mmol·L^-1 H₂O₂, and 808 nm NIR was 81.1%, significantly higher than either factor alone. These hydrogels show promise as an injectable dressing for chronic wounds, effectively integrating the internal microenvironment of the wound tissue with external NIR to modulate drug release.