NIR-responsive injectable nanocomposite hydrogels with enhanced angiogenesis for promoting full-thickness wound healing

Angiogenesis plays a vital role in the treatment of full-thickness wounds. Deferoxamine (DFO) has been employed to promote neovascularization, however, smart drug delivery systems are needed to optimize its utilization. In this study, an injectable extracellular matrix (ECM)-mimicking hydrogel (HOG@P&D) was developed by leveraging the dynamic Schiff base and hydrogen bonds among a chitosan derivative (HACC), oxidized alginate (OSA), gelatin, and DFO-loaded polydopamine nanoparticles (P&D) for efficient wound healing. The incorporation of P&D enables HOG@P&D to respond to near-infrared (NIR) irradiation, converting laser energy into heat to trigger an on-demand, rapid release of DFO, thereby effectively enhancing angiogenesis. In vitro tube formation assays revealed that the number of meshes in the HOG@P&D group was fourfold higher than that of the control group. Additionally, HOG@P&D exhibited superior mechanical properties, tissue adhesion, and injectability, allowing it to cover wounds seamlessly. This hydrogel also demonstrated antibacterial and antioxidant properties, creating a conducive microenvironment for wound healing. In vivo studies further confirmed that HOG@P&D promoted angiogenesis and mitigated inflammation by upregulating angiogenic growth factor expression, thereby accelerating full-thickness wound healing. This nanocomposite hydrogel shows significant potential as a high-performance wound dressing.