Copper-Based Metal–Organic Framework as a Controllable Nitric Oxide-Releasing Vehicle for Enhanced Diabetic Wound Healing

Abstract

Chronic wounds are one of the most serious complications of diabetes mellitus. Even though utilizing nitric oxide (NO) as a gas medicine to repair diabetic wounds presents a promising strategy, controlling the NO release behavior in the affected area, which is vital for NO-based therapy, still remains a significant challenge. In this work, a copper-based metal–organic framework, namely, HKUST-1, has been introduced as a NO-loading vehicle, and a NO sustained release system with the core–shell structure has been designed through the electrospinning method. The results show that the NO is quantificationally and stably loaded in the HKUST-1 particles, and the NO-loaded HKUST-1 particles are well incorporated into the core layer of the coaxial nanofiber. Therefore, NO can be controllably released with an average release rate of 1.74 nmol L–1 h–1 for more than 14 days. Moreover, the additional copper ions released from the degradable HKUST-1 play a synergistic role with NO to promote endothelial cell growth and significantly improve the angiogenesis, collagen deposition as well as anti-inflammatory property in the wound bed, which eventually accelerate the diabetic wound healing. These results suggest that such a copper-based metal–organic framework material as a controllable NO-releasing vehicle is a highly efficient therapy for diabetic wounds.