Hierarchical Acceleration of Wound Healing through Intelligent Nanosystem to Promote Multiple Stages

Wound healing is a dynamic, interactive, and complex process, including multiple stages. Although various nanomaterials are applied to accelerate the wound healing process through exhibiting antibacterial activity or promoting cell proliferation, only a single stage is promoted during the process, lowering healing efficacy. It is necessary to develop programmable nanosystems for promoting multiple wound healing stages in sequence. Herein, arginine-loaded and detachable ceria-graphene nanocomposites ((A)CG NCs) were designed to achieve this purpose. Ceria NPs and graphene were linked by base-cleavable N-hydroxysuccinimide ester. At inflammation stage, (A)CG NCs could effectively generate reactive oxygen species (ROS) and kill bacteria under white light irradiation due to their efficient electron-hole separation between ceria NPs and graphene. At proliferation stage, ceria NPs could be detached from (A)CG NCs and taken up by cells to scarify intracellular ROS and promote cell proliferation, while the separated graphene could act as a scaffold to promote fibroblast migration to wound site. A series of in vitro and in vivo assessments demonstrated that (A)CG NCs could effectively accelerate wound healing process.