Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.
Biomater Sci. 2020 Jun 21;8(12):3404-3417. doi: 10.1039/d0bm00566e. Epub 2020 May 7.
Although titanium-based implants are widely used in orthopedic and dental clinics, improved osseointegration at the bone-implant interface is still required. In this study, we developed a titanium alloy (Ti-6Al-4V, Ti) coated with epigallocatechin gallate (EGCG) and magnesium ions (Mg) in a metal-polyphenol network (MPN) formation. Specifically, Ti discs were coated with EGCG in MgCl by controlling their concentrations and pH, with the amount of coating increasing with the coating time. An in vitro culture of human adipose-derived stem cells (hADSCs) on the EGCG-Mg-coated Ti showed significantly enhanced ALP activity and mRNA expression of osteogenic markers. In addition, the EGCG-Mg-coated Ti enhanced the mineralization of hADSCs, significantly increasing the calcium content (22.2 ± 5.0 μg) compared with cells grown on Ti (13.5 ± 0.3 μg). Treatment with 2-APB, an inhibitor of Mg signaling, confirmed that the enhancement of osteogenic differentiation in the hADSCs was caused by the synergistic influence of EGCG and Mg. The EGCG-Mg coating significantly reduced the osteoclastic maturation of Raw264.7 cells, reducing tartrate-resistant acid phosphatase activity (5.4 ± 0.4) compared with that of cells grown on Ti (1.0 ± 0.5). When we placed Ti implants onto rabbit tibias, the bone-implant contact (%) was greater on the EGCG-Mg-coated Ti implants (8.1 ± 4.3) than on the uncoated implants (4.4 ± 2.0). Therefore, our MPN coating could be a reliable surface modification for orthopedic implants to enable the delivery of an osteoinductive metal ion (Mg) with the synergistic benefits of a polyphenol (EGCG).
虽然钛基植入物在骨科和牙科诊所中得到广泛应用,但仍需要改善骨-植入物界面的骨整合。在这项研究中,我们开发了一种钛合金(Ti-6Al-4V,Ti),它在金属-多酚网络(MPN)形成中涂有表没食子儿茶素没食子酸酯(EGCG)和镁离子(Mg)。具体来说,Ti 盘通过控制其浓度和 pH 值在 MgCl 中涂覆 EGCG,随着涂层时间的增加,涂层量增加。在 EGCG-Mg 涂层 Ti 上培养人脂肪来源的干细胞(hADSCs)的体外培养显示出明显增强的碱性磷酸酶活性和成骨标志物的 mRNA 表达。此外,EGCG-Mg 涂层 Ti 增强了 hADSCs 的矿化作用,与在 Ti 上生长的细胞相比(13.5 ± 0.3 μg),钙含量显著增加(22.2 ± 5.0 μg)。用 2-APB(Mg 信号抑制剂)处理证实了 hADSCs 成骨分化的增强是由 EGCG 和 Mg 的协同影响引起的。EGCG-Mg 涂层显著降低了 Raw264.7 细胞的破骨细胞成熟,与在 Ti 上生长的细胞相比(1.0 ± 0.5),抗酒石酸酸性磷酸酶活性降低(5.4 ± 0.4)。当我们将 Ti 植入物放置在兔子胫骨上时,EGCG-Mg 涂层 Ti 植入物的骨-植入物接触(%)(8.1 ± 4.3)大于未涂层植入物(4.4 ± 2.0)。因此,我们的 MPN 涂层可以作为一种可靠的骨科植入物表面改性方法,将具有协同益处的骨诱导金属离子(Mg)与多酚(EGCG)一起输送。