Bioabsorbable zinc ion induced biphasic cellular responses in vascular smooth muscle cells

Bioabsorbable metal zinc (Zn) is a promising new generation of implantable scaffold for cardiovascular and orthopedic applications. In cardiovascular stent applications, zinc ion (Zn²⁺) will be gradually released into the surrounding vascular tissues from such Zn-containing scaffolds after implantation. However, the interactions between vascular cells and Zn²⁺ are still largely unknown. We explored the short-term effects of extracellular Zn²⁺ on human smooth muscle cells (SMCs) up to 24 h, and an interesting biphasic effect of Zn²⁺ was observed. Lower concentrations (<80 μM) of Zn²⁺ had no adverse effects on cell viability but promoted cell adhesion, cell spreading, cell proliferation, cell migration, and enhanced the expression of F-actin and vinculin. Cells treated with such lower concentrations of Zn²⁺ displayed an elongated shape compared to controls without any treatment. In contrast, cells treated with higher Zn²⁺ concentrations (80-120 μM) had opposite cellular responses and behaviors. Gene expression profiles revealed that the most affected functional genes were related to angiogenesis, inflammation, cell adhesion, vessel tone, and platelet aggregation. Results indicated that Zn has interesting concentration-dependent biphasic effects on SMCs with low concentrations being beneficial to cellular functions.