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

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.