Cobalt-based metal-organic framework as a dual cooperative controllable release system for accelerating diabetic wound healing
Cobalt-based metal-organic framework as a dual cooperative controllable release system for accelerating diabetic wound healing
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DOI：
10.1007/s12274-020-2846-1
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发表时间：
2020-06-16
期刊：
影响因子：
9.9
通讯作者：
Xu, He
中科院分区：
文献类型：
--
作者：
Li, Jiankai;Lv, Fang;Xu, He
糖尿病慢性创面血管生成不足是造成创面不能自愈的重要原因之一。在这项工作中，引入了钴基金属有机框架（ZIF-67）作为载体来装载促血管生成的小分子药物（二甲基氧基酰甘氨酸，DMOG）。为了实现糖尿病伤口床的长期血管生成治疗，我们设计了一种双协同可控释放系统，将负载药物的ZIF-67纳米颗粒加入到微图案PLLA/明胶纳米纤维支架中。结果表明，DMOG以较高的载药率（359.12 mg/g）掺入ZIF-67中，载药的ZIF-67纳米颗粒包埋在圆形支架中。值得注意的是，DMOG和Co离子可以从支架中连续释放超过15天。体外实验表明，微图纳米纤维支架释放的Co离子和DMOG可通过诱导缺氧反应和上调HIF-1 α、VEGF和e-NOS等血管生成相关基因的表达，协同促进人脐静脉内皮细胞（HUVECs）的增殖、迁移和成管。此外，他们的体内实验结果表明，复合支架可以显著促进糖尿病创面血管生成、胶原沉积和消除炎症。这些结果表明，钴基金属-有机骨架作为一种双重协同可控释放系统，为促进血管生成和促进糖尿病创面愈合提供了新的策略。
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. Thein vitrostudies 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-1 alpha, VEGF and e-NOS. Furthermore, thein vivoresults 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.