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.

糖尿病慢性伤口的血管生成不足是导致伤口无法自愈的最重要原因之一。在这项工作中，引入了基于钴的金属有机骨架（ZIF-67）作为载体，以加载促血管生成的小分子药物（二甲基草酰甘氨酸，DMOG）。为了在糖尿病伤口床上实现长期的血管生成治疗，已通过将载有药物的ZIF-67纳米颗粒掺入微图案化的PLLA /明胶纳米纤维支架中，设计了一种双重协同可控释放系统。结果表明，将DMOG以高负载比（359.12 mg / g）掺入ZIF-67中，并且将负载药物的ZIF-67纳米颗粒很好地嵌入圆形构图支架中。值得注意的是 DMOG以及Co离子可能会从支架上连续释放超过15天。的体外研究表明，微模式纳米纤维支架释放的Co离子和DMOG可以通过诱导缺氧反应并上调血管生成相关基因的表达来协同促进人脐静脉内皮细胞（HUVEC）的增殖，迁移和管形成。如HIF-1α，VEGF和e-NOS。此外，体内结果表明复合支架可以显着增强血管生成，胶原蛋白沉积并消除糖尿病伤口中的炎症。这些结果表明，基于钴的金属-有机框架作为双重协同可控释放系统提供了增强血管生成和促进糖尿病伤口愈合的新策略。