Endothelial Cellular Responses to Biodegradable Metal Zinc

Biodegradable zinc (Zn) metals, a new generation of biomaterials, have attracted much attention due to their excellent biodegradability, bioabsorbability, and adaptability to tissue regeneration. Compared with magnesium (Mg) and iron (Fe), Zn exhibits better corrosion and mechanical behaviors in orthopedic and stent applications. After implantation, Zn containing material will slowly degrade, and Zn ions (Zn²⁺) will be released to the surrounding tissue. For stent applications, the local Zn²⁺concentration near endothelial tissue/cells could be high. However, it is unclear how endothelia will respond to such high concentrations of Zn²⁺, which is pivotal to vascular remodeling and regeneration. Here, we evaluated the short-term cellular behaviors of primary human coronary artery endothelial cells (HCECs) exposed to a concentration gradient (0-140 μM) of extracellular Zn²⁺. Zn²⁺ had an interesting biphasic effect on cell viability, proliferation, spreading, and migration. Generally, low concentrations of Zn²⁺ promoted viability, proliferation, adhesion, and migration, while high concentrations of Zn²⁺ had opposite effects. For gene expression profiles, the most affected functional genes were related to cell adhesion, cell injury, cell growth, angiogenesis, inflammation, vessel tone, and coagulation. These results provide helpful information and guidance for Zn-based alloy design as well as the controlled release of Zn²⁺in stent and other related medical applications.