Phase-change Composite Filled Natural Nanotubes in Hydrogel Promote Wound Healing Under Photothermally Triggered Drug Release

It is of great importance to treat a bacterial-infected wound by a smart dressing capable of delivering antibiotics in a smart manner without causing drug resistance. The construction of smart release nanocontainers responsive to near-infrared (NIR) laser irradiation in an on-demand and stepwise way is a promising strategy for avoiding the emergence of multidrug-resistant bacteria. Here, we develop a hydrogel composite made of alginate and nanotubes with an efficient NIR-triggered release of rifampicin and outstanding antibacterial ability. This composite hydrogel is prepared through co-encapsulating antibacterial drug (rifampicin), NIR-absorbing dye (indocyanine green), and phase-change materials (a eutectic mixture of fatty acids) into halloysite nanotubes, followed by incorporation into alginate hydrogels, allowing the in-situ gelation at room temperature and maintaining the integrity of drug-loaded nanotubes. Among them, the eutectic mixture with a melting point of 39 °C serves as the biocompatible phase-change material to facilitate the NIR-triggered drug release. The resultant phase-change material gated-nanotubes exhibit a prominent photothermal efficiency with multistep drug release under laser irradiation. In an assay, composite hydrogel provides good antibacterial potency against one of the most prevalent microorganisms of dangerous gas gangrene. A bacterial-infected rat full-thickness wound model demonstrates that the NIR-responsive composite hydrogel inhibits the bacteria colonization and suppresses the inflammatory response caused by bacteria, promoting angiogenesis and collagen deposition to accelerate wound regeneration. The NIR-responsive composite hydrogel has a great potential as an antibacterial wound dressing functionalized with controlled multistep treatment of the infected sites.