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

Abstract

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.

Magnesium ion leachables induce a conversion of contractile vascular smooth muscle cells to an inflammatory phenotype

“…Compared to vascular endothelial cells, vSMCs were much less tolerable to the corroded products of zinc in vivo . In vitro , vSMCs replicated slower when cultured at 80∼120 μM zinc ion concentration . Even when Zn 2+ was low to 50 m M , the proliferative damage still occurred in a long‐term exposure experiment .…”

“…Even when Zn 2+ was low to 50 m M , the proliferative damage still occurred in a long‐term exposure experiment . In addition, the free Zn 2+ also hindered the cell movement of human aortic SMCs . Therefore, the locally accumulated Zn 2+ due to the degradation of AZ31 may inhibit the vSMC expanding.…”

“…In our work, the Mg ions exhibited the proinflammatory activity for the contractile vSMCs. Recently, Ma et al performed cDNA microarrays and showed that Mg 2+ and Zn 2+ altered the expressions of the inflammation‐related genes in vSMCs, including Vcam1, Ccl2 , and Il1b. These studies all suggest the bioevaluation of the Mg‐based stents need to cover their modulation of the critical phenotypes of vSMCs.…”

The Prospects of Zinc as a Structural Material for Biodegradable Implants—A Review Paper

“…In contrast, high concentrations of Zn 2+ elicited opposite effects. Gene expression profiles revealed that the most affected functional genes were related to angiogenesis, inflammation, cell adhesion, vessel tone, and platelet aggregation [26]. Since the Zn 2+ concentration is intrinsically related to the implant degradation rate, a slow corrosion rate with controlled release of Zn 2+ is desirable to maintain a low concentration profile of Zn 2+ in the local tissues, in order to benefit cellular functions [16].…”

“…The cellular response of human bone marrow mesenchymal stem cells (hMSC) and human vascular cells (HCECs, HASMC, HAEC) to Zn 2+ was recently investigated [16,26,69,70]. According to Zhu et al [70], Zn biomaterial can support hMSC adhesion and proliferation and zinc ions can lead to enhanced regulation of genes, cell survival/growth and differentiation, extracellular matrix (ECM) mineralization, and osteogenesis.…”