Effects of Zinc Ions Released From Ti-NW-Zn Surface on Osteogenesis and Angiogenesis In Vitro and in an In Vivo Zebrafish Model

Abstract

Zinc-modified titanium materials have been widely applied in oral implants. Among them, our previous studies have also successfully prepared a novel acid-etched microstructured titanium surface modified with zinc-containing nanowires (Ti-NW-Zn) and proved its excellent biocompatibility. It is well known that the functional regulation between angiogenesis and osteogenesis is of great importance for bone remodeling around implants. However, there are few reports concerning the biological safety of zinc ions released from materials and the appropriate concentration of released zinc ions which was more conducive to angiogenesis and bone regeneration. In this study, we investigated the effects of zinc ions released from Ti-NW-Zn surfaces on angiogenesis and osteogenesis using the zebrafish model and revealed the relationship between angiogenesis and osteogenesis via HUVECs and MC3T3-E1s in vitro. We found that the zinc ions released from Ti-NW-Zn surfaces, with a concentration lower than median lethal concentrations (LCs) of zebrafish, were biologically safe and promote osteogenesis and angiogenesis in vivo. Moreover, the proper concentration of zinc ions could induce the proliferation of HUVECs and osteogenic differentiation. The positive effects of the appropriate concentration of zinc ions on osteoblast behaviors might be regulated by activating the MAPK/ERK signaling pathway. These aspects may provide new sights into the mechanisms underlying zinc-modified titanium surfaces between osteogenesis and angiogenesis, to lay the foundation for further improving the materials, meanwhile, promoting the applications in dentistry.

A functional study of zinc–titanium coatings and exploration of the intrinsic correlation between angiogenesis and osteogenesis

“…It has been shown that the regulatory effect of zinc ions on osteogenesis is closely related to the MAPK/ERK signaling pathway. 24 The results show that our prepared Zn-containing micro-arc oxide coatings have sound osteogenic effects. The osteogenic effect of the Zn2 group was collectively superior to that of the remaining groups.…”

“…It is pointed out that adding zinc to titanium on the surface can improve the material's antibacterial properties and chemical stability. 24…”

“…Studies have shown that appropriate concentrations of zinc ions can stimulate the upstream of the MAPK signaling axis, activating MAPK phosphorylation, and once activated, the MAPK signaling pathway responds and triggers further responses in a cascade fashion, ultimately affecting the expression of osteogenic markers. 24 In this study, MAO technology successfully combines zinc elements from the electrolyte into the titanium coating. The Zn2 group had a higher Zn content than the Zn1 group.…”

“…The preparation of conditioned media was referred to in the relevant literature. 24 The secretions of HUVECs and BMSCs were collected to prepare a conditioned medium (CM), and their functional effects on each other were studied. The impact of HUVECs secretion on osteogenic differentiation of BMSCs under different concentrations of zinc ions was verified by q-PCR.…”

“…It is pointed out that adding zinc to titanium on the surface can improve the material's antibacterial properties and chemical stability. 24 Micro-arc oxidation allows the attachment of elements from the electrolyte into the surface coating of the titanium sheet. In the case of zinc acetate added to the electrolyte, the element zinc is present in the form of ions, which can likewise be bound to the titanium sheet surface layer by MAO.…”