Hollow, Rough, and Nitric Oxide-Releasing Cerium Oxide Nanoparticles for Promoting Multiple Stages of Wound Healing.

Wound healing is a complex and sequential biological process that involves multiple stages. Although various nanomaterials are applied to accelerate the wound healing process, only a single stage is promoted during the process, lacking hierarchical stimulation. Herein, hollow CeO2 nanoparticles (NPs) with rough surface and l-arginine inside (Ah CeO2 NPs) are developed as a compact and programmable nanosystem for sequentially promoting the hemostasis, inflammation, and proliferation stages. The rough surface of Ah CeO2 NPs works as a nanobridge to rapidly closure the wounds, promoting the hemostasis stage. The hollow structure of Ah CeO2 NPs enables the multireflection of light inside particles, significantly enhancing the light harvest efficiency and electron-hole pair abundance. Simultaneously, the porous shell of Ah CeO2 NPs facilitates the electron-hole separation and reactive oxygen species production, preventing wound infection and promotion wound healing during the inflammation stage. The enzyme mimicking property of Ah CeO2 NPs can alleviate the oxidative injury in the wound, and the released l-arginine can be converted into nitric oxide (NO) under the catalysis of inducible NO synthase, both of which promote the proliferation stage. A series of in vitro and in vitro biological assessments corroborate the effectiveness of Ah CeO2 NPs in the wound healing process.