Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, College of Biological Science and Technology, National Yang Ming Chiao Tung University, 75 Bo-Ai Street, Hsinchu 300, Taiwan.
Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, 75 Bo-Ai Street, Hsinchu 300, Taiwan.
Bioconjug Chem. 2023 Sep 20;34(9):1688-1703. doi: 10.1021/acs.bioconjchem.3c00325. Epub 2023 Aug 8.
The employment of metal-organic framework (MOF)-based nanomaterials has been rapidly increasing in bioapplications owing to their biocompatibility, drug degradation, tunable porosity, and intrinsic biodegradability. This evidence suggests that the multifunctional bimetallic ions can behave as remarkable candidates for infection control and wound healing. In this study, bimetallic MOFs (Zn-HKUST-1 and FolA-Zn-HKUST-1) embedded with and without folic acid were synthesized and used for tissue sealing and repairing incisional wound sites in mice models. For comparison, HKUST-1 and FolA-HKUST-1 were also synthesized. The Brunauer-Emmett-Teller (BET) surface area measured for HKUST-1, FolA-HKUST-1, Zn-HKUST-1, and FolA-Zn-HKUST-1 from N isotherms was found to be 1868, 1392, 1706, and 1179 m/g, respectively. The measurements of contact angle values for Zn-HKUST-1, FolA-HKUST-1, and Zn-FolA-HKUST-1 were identified as 4.95 ± 0.8, 43.6 ± 3.4, and 60.62 ± 2.0°, respectively. For topical application in wound healing, they display a wide range of healing characteristics, including antibacterial and enhanced wound healing rates. In addition, cell migration and tubulogenic potentials were evaluated. The significant reduction in the wound gap and increased expression levels for CD31, eNOS, VEGF-A, and Ki67 were observed from immunohistological analyses to predict the angiogenesis behavior at the incision wound site. The wound healing rate was analyzed in the excisional dermal wounds of diabetic mice model . On account of antibacterial potentials and tissue-repairing characteristics of Cu and Zn ions, designing an innovative mixed metal ion-based biomaterial has wide applicability and is expected to modulate the growth of various gradient tissues.
基于金属有机骨架(MOF)的纳米材料由于其生物相容性、药物降解、可调节的孔隙率和内在的可生物降解性,在生物应用中的应用迅速增加。有证据表明,多功能双金属离子可以作为控制感染和伤口愈合的显著候选物。在这项研究中,合成了嵌入和不嵌入叶酸的双金属 MOF(Zn-HKUST-1 和 FolA-Zn-HKUST-1),并将其用于小鼠模型的组织密封和修复切口伤口部位。为了比较,还合成了 HKUST-1 和 FolA-HKUST-1。从 N 等温线测量的 HKUST-1、FolA-HKUST-1、Zn-HKUST-1 和 FolA-Zn-HKUST-1 的 Brunauer-Emmett-Teller(BET)表面积分别为 1868、1392、1706 和 1179 m/g。Zn-HKUST-1、FolA-HKUST-1 和 Zn-FolA-HKUST-1 的接触角值测量值分别确定为 4.95±0.8、43.6±3.4 和 60.62±2.0°。对于局部应用于伤口愈合,它们表现出广泛的愈合特征,包括抗菌和增强的伤口愈合率。此外,还评估了细胞迁移和管状形成潜力。从免疫组织学分析中观察到伤口间隙的显著减少和 CD31、eNOS、VEGF-A 和 Ki67 的表达水平增加,以预测切口部位的血管生成行为。在糖尿病小鼠模型的皮肤切除伤口中分析了伤口愈合率。鉴于铜和锌离子的抗菌潜力和组织修复特性,设计创新的混合金属离子基生物材料具有广泛的适用性,并有望调节各种梯度组织的生长。