Hierarchical micro/nanofibrous scaffolds incorporated with curcumin and zinc ion eutectic metal organic frameworks for enhanced diabetic wound healing via anti-oxidant and anti-inflammatory activities

Abstract Persistent excessive inflammation and oxidative stress are main causes for the impaired wound healing in diabetic patient. To reduce the excessive reactive oxygen species (ROS) and inflammatory response of wound in acute inflammatory phase is a key strategy for diabetic wound healing. In this work, a kind of metal organic frameworks (MOFs) with curcumin as ligand and Zn2+ as center were synthesized by a eutectic method, and a controllable double release system of curcumin and Zn2+ for diabetic wound repair was constructed by loading the MOFs into the hierarchical micro/nanofibrous poly (L-lactic acid) (PLLA) scaffolds. The results showed that the synthetic MOFs could significantly improve the bioavailability of curcumin, and the fabricated hierarchical micro/nanofibrous scaffolds could not only promote the adhesion and growth of skin tissue cells, but also release curcumin and Zn2+ on-demand in the early stage of inflammation. In vivo experiments further demonstrated that the scaffolds could effectively inhibit the inflammatory response and promote collagen deposition, angiogenesis as well as re-epithelialization of the skin wound, which ultimately promoted diabetic would healing in mice. The mechanism lying behind is closely related to the finding that ROS generation and inflammatory reaction in the acute inflammation stage of wound healing were significantly reduced by the scaffolds. Our results suggest that the designed hierarchical micro/nanofibrous scaffolds with curcumin and Zn2+ eutectic MOFs incorporated can effectively promote the skin wound healing in diabetic mice, providing a new strategy for the treatment of chronic wound.