Department of Biomedical Sciences and Engineering, National Central University, Jhong-Li, Taoyuan, 320, Taiwan.
Department of Chemical and Materials Engineering, National Central University, Jhong-Li, Taoyuan, 320, Taiwan.
Sci Rep. 2019 Aug 9;9(1):11562. doi: 10.1038/s41598-019-47978-9.
In this study, we report a metallogel developed based on metal-phenolic coordination of natural low-cost polyphenolic molecule and metal ions. Gelation occurs by mixing tannic acid (TA) and group (IV) titanium ions (Ti) to form TA-Ti gel. The TA-Ti gel exhibits good capability to incorporate diverse metal ions by in situ co-gelation. Herein, five antimicrobial metal ions, i.e. ferric (Fe), copper (Cu), zinc (Zn), cobalt (Co) and nickel (Ni) ions, were employed to include in TA-Ti gels for developing intelligent dressings for infected wounds. The chemical and coordinative structures of TA-Ti metallogels were characterized by UV-Vis and Fourier-transform infrared (FT-IR) spectroscopies. Cytotoxicity of antimicrobial metallogels was explored by MTT assay with NIH 3T3 fibroblasts. The release of metal ions was evaluated by inductively coupled plasma mass spectrometry (ICP-MS), indicating the different releasing profiles upon the coordinative interactions of metal ions with TA. The formation and disassembly of metallogels are sensitive to the presence of acid and an oxidizer, HO, which are substances spontaneously generated in infected wounds due to the metabolic activity of bacteria and the intrinsic immune response. The Cu releasing rates of TA-Ti-Cu metallogels at different pH values of 5.5, 7.4 and 8.5 have been studied. In addition, addition of HO trigger fast release of Cu as a result of oxidation of galloyl groups in TA. Consequently, the antimicrobial potency of TA-Ti-Cu metallogels can be simultaneously activated while the wounds are infected and healing. The antimicrobial property of metallogels against Gram-negative Escherichia coli, and Gram-positive Methicillin-Resistant Staphylococcus aureus (USA300) and Staphylococcus epidermidis has been investigated by agar diffusion test. In an animal model, the TA-Ti-Cu metallogels were applied as dressings for infected wounds, indicating faster recovery in the wound area and extremely lower amount of bacteria around the wounds, compared to TA-Ti gels and gauze. Accordingly, the intelligent nature derived metallogels is a promising and potential materials for medical applications.
在这项研究中，我们报告了一种基于天然低价位多酚分子与金属离子的金属-酚配位开发的金属凝胶。通过混合单宁酸（TA）和第（IV）族钛离子（Ti）形成 TA-Ti 凝胶来发生凝胶化。TA-Ti 凝胶通过原位共凝胶化表现出良好的掺入多种金属离子的能力。在此，使用五种抗菌金属离子，即铁（Fe）、铜（Cu）、锌（Zn）、钴（Co）和镍（Ni）离子，将其包含在 TA-Ti 凝胶中，用于开发用于感染伤口的智能敷料。通过 NIH 3T3 成纤维细胞的 MTT 测定法研究了抗菌金属凝胶的细胞毒性。通过电感耦合等离子体质谱法（ICP-MS）评估了金属离子的释放，表明金属离子与 TA 的配位相互作用导致不同的释放曲线。金属凝胶的形成和分解对酸和氧化剂 HO 的存在敏感，HO 是由于细菌的代谢活动和固有免疫反应，在感染的伤口中自发产生的物质。研究了 TA-Ti-Cu 金属凝胶在 pH 值为 5.5、7.4 和 8.5 时的 Cu 释放率。此外，HO 的加入会由于 TA 中的没食子酰基氧化而快速释放 Cu。因此，当伤口感染和愈合时，TA-Ti-Cu 金属凝胶的抗菌效力可以同时被激活。通过琼脂扩散试验研究了金属凝胶对革兰氏阴性大肠杆菌、耐甲氧西林金黄色葡萄球菌（USA300）和表皮葡萄球菌的抗菌性能。在动物模型中，将 TA-Ti-Cu 金属凝胶用作感染伤口的敷料，与 TA-Ti 凝胶和纱布相比，伤口区域的恢复更快，伤口周围的细菌数量极低。因此，衍生出的智能金属凝胶是一种有前途和有潜力的医疗应用材料。
