Platinum nanozyme embedded in hyaluronate with multifunctional attributes synergistically promoting tracheal fistula...

Respiratory tract fistulas, including tracheal and bronchial fistulas, usually cause prolonged hospitalization with developed complications and even death, while respiratory tract fistula healing remains challenging. Exploring effectiveness and mechanism in animal systems using well-designed bio-nanomaterials will improve our understanding of fistula management. Hyaluronate (hyaluronan or hyaluronic acid) has been widely studied as a promising coating material for bio-nanomaterials in treatment applications. Herein, by combining the intrinsic bioactivities of sodium hyaluronate (SHA) and the enzyme-like activities of platinum (Pt) nanoparticles (NPs), obtained SHA-PtNPs defined as nanozymes (Enzyme-like nanomaterials) have been proposed to treat tracheal fistulas. Results reveal that introducing SHA endows the fabrication of PtNPs with dispersibility, small particle size (3.7 nm), stability, etc. On the other hand, SHA-PtNPs present high catalase-like (3320 U/g), superoxide dismutase-like activities (129,000 U/g), and hydroxyl radicals elimination capacity, thereby exerting excellent reactive oxide species scavenging ability. We have systematically verified the above properties of SHA-PtNPs in vitro. SHA-PtNPs show outstanding biocompatibility, promote cell proliferation and migration, and have considerable hemocompatibility and hemostasis. Afterward, rabbit tracheal fistula models that were treated with SHA-PtNPs in vivo showed a significant improvement in the closure of the fistulas and an increase in quality. This was evident through a substantial decrease in inflammation, increased angiogenesis, stimulation of re-epithelialization, and highly ordered alignment of collagen fibers. No significant side effects were observed. In summary, this work initiates an in vivo treatment for tracheal fistula models by taking advantage of both naturally sourced polysaccharides and nanozymes.