Injectable Thermosensitive Composite Hydrogels for Sustained Nanoparticle Delivery and Enhanced Wound Healing

Wound healing is frequently compromised by excessive oxidative stress, prolonged inflammation, and inadequate tissue regenerative capacity. To address these challenges, a thermosensitive and injectable composite hydrogel based on Pluronic F127 (F127), phosphatidylcholine (PC), and L-lysine (Lys) was developed for the sustained delivery of sinomenine-gallic acid nanoparticles (SGNPs) and the acceleration of wound repair. The hydrogel undergoes a rapid sol-gel transition at physiological temperatures through physical interactions, enabling excellent injectability and <i>in situ</i> gelation. The optimized composite hydrogel exhibited improved mechanical properties, enhanced structural stability, and a uniform porous microarchitecture. The F127-Lys-PCF127-Lys-PC@SGNPs hydrogel showed superior overall stability and hemocompatibility while enabling the sustained release of SGNPs for up to 24 h. Benefiting from the incorporation of SGNPs, the composite hydrogel displayed enhanced antioxidant activity, effectively scavenging free radicals and alleviating cellular oxidative stress. <i>In vitro</i> experiments demonstrated that the hydrogel promoted keratinocyte migration and proliferation. Furthermore, in a murine full-thickness skin wound model, treatment with F127-Lys-PCF127-Lys-PC@SGNPs significantly accelerated wound closure and facilitated re-epithelialization, angiogenesis, and collagen deposition. Collectively, this multifunctional thermosensitive hydrogel provides a promising platform for advanced wound dressings that integrate sustained delivery, antioxidant protection, and tissue regeneration.