Surface engineering of titanium alloy using metal-polyphenol network coating with magnesium ions for improved osseointegration

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 (Mg2+) in a metal-polyphenol network (MPN) formation. Specifically, Ti discs were coated with EGCG in MgCl2 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-Mg2+-coated Ti showed significantly enhanced ALP activity and mRNA expression of osteogenic markers. In addition, the EGCG-Mg2+-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 Mg2+ signaling, confirmed that the enhancement of osteogenic differentiation in the hADSCs was caused by the synergistic influence of EGCG and Mg2+. The EGCG-Mg2+ 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-Mg2+-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 (Mg2+) with the synergistic benefits of a polyphenol (EGCG).