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

Abstract

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 (AhCeO2 NPs) are developed as a compact and programmable nanosystem for sequentially promoting the hemostasis, inflammation, and proliferation stages. The rough surface of AhCeO2 NPs works as a nanobridge to rapidly closure the wounds, promoting the hemostasis stage. The hollow structure of AhCeO2 NPs enables the multireflection of light inside particles, significantly enhancing the light harvest efficiency and electron–hole pair abundance. Simultaneously, the porous shell of AhCeO2 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 AhCeO2 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 AhCeO2 NPs in the wound healing process.

Efficacy of A Novel Smart Polymeric Nanodrug in the Treatment of Experimental Wounds in Rats

“…The presence of a polymer gel in cerium dioxide nanoparticles with changing valency in the wound ensures the environment required for regeneration as a result of its anti-inflammatory, antioxidant, antimicrobial, and proregenerative effects. The decrease in the active forms of oxygen can be judged by the decrease in the number of non-resident cells (leukocytes), which are the main producers of free radicals in the wound, which is consistent with the conclusions from different groups of scientists [39][40][41]. The positive effects of CeO 2 that are relevant for regenerative medicine are consistent with the results of other studies [19][20][21][22][23][24]27,42].…”

Cerium Oxide Nanoparticles: Recent Advances in Tissue Engineering

“…However, what matters most in tissue engineering is the manufacturing of vascularized and innervated tissues, which has not been well addressed as yet. To this end, both synthesis and fabrication techniques should be integrated into the hierarchical stimulation of angiogenesis and differentiation processes, as shown previously for the use of Ah CeONPs in wound healing [151].…”

“…In another study, the wound nanobridge was explored by applying CeONPs with hollow and porous shells (termed as Ah CeONPs) [151]. This novel product originated from the hierarchical stimulation of the wound healing process, including the hemostasis, inflammation, and proliferation stages.…”

The Chemistry of Reticular Framework Nanoparticles: MOF, ZIF, and COF Materials

“…NO is produced in cells, e.g., by the NO synthase at varied concentrations in the nano-to micromolar range and acts as neurotransmitter in the peripheral and central nervous system, [323] anticoagulant agent, [326] and stimulus for tissue growth and wound healing. [327] Moreover, NO possesses antibacterial [328] properties and regulates inflammatory processes [329] and tumor progression [330] depending on concentration [331] and site in the body. Due to its strong biomedical importance, great effort has gone into the design of reticular nanoparticles that release NO in a controllable fashion.…”