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 (_ACG NCs) were designed to achieve this purpose. Ceria NPs and graphene were linked by base-cleavable N-hydroxysuccinimide ester. At inflammation stage, _ACG 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 _ACG 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 _ACG NCs could effectively accelerate wound healing process.