Cobalt-based metal-organic framework as a dual cooperative controllable release system for accelerating diabetic wound healing

Insufficient angiogenesis in the chronic wound of the diabetic is one of the most important causes that making the wound unable to heal itself. In this work, a cobalt-based metal-organic framework (ZIF-67) was introduced as a carrier for loading a pro-angiogenic small molecular drug (dimethyloxalylglycine, DMOG). To achieve a long-term angiogenic therapy on the diabetic wound beds, a dual cooperative controllable release system has been designed by incorporating the drug-loaded ZIF-67 nanoparticles into the micro-patterned PLLA/Gelatin nanofibrous scaffolds. The results showed that DMOG was incorporated into ZIF-67 with a high loading ratio (359.12 mg/g), and the drug-loaded ZIF-67 nanoparticles were well embedded in the circular patterned scaffold. Notably, the DMOG as well as Co ions could continuously release from the scaffold for more than 15 days. The in vitro studies showed that the released Co ions and DMOG from the micropatterned nanofibrous scaffolds could synergistically promote the proliferation, migration and tube formation of the human umbilical vein endothelial cells (HUVECs) by inducing a hypoxia response and upregulating the expression of angiogenesis-related genes such as HIF-1α, VEGF and e-NOS. Furthermore, the in vivo results demonstrated that the composite scaffolds could significantly enhance angiogenesis, collagen deposition and eliminate inflammation in the diabetes wounds. These results indicate that the cobalt-based metal-organic framework as a dual cooperative controllable release system provides a new strategy for enhancing angiogenesis and promoting diabetic wound healing.