In Vitro Cytotoxicity, Adhesion, and Proliferation of Human Vascular Cells Exposed to Zinc

Abstract

Zinc (Zn) and its alloys have recently been introduced as a new class of biodegradable metals with potential application in biodegradable vascular stents. Although an in vivo feasibility study pointed to outstanding biocompatibility of Zn-based implants in vascular environments, a thorough understanding of how Zn and Zn2+ affect surrounding cells is lacking. In this comparative study, three vascular cell types—human endothelial cells (HAEC), human aortic smooth muscle cells (AoSMC), and human dermal fibroblasts (hDF)—were studied to advance the understanding of Zn/Zn2+-cell interactions. Aqueous cytotoxicity using a Zn2+ insult assay resulted in LD50 values of 50 µM for hDF, 70 µM for AoSMC, and 265 µM for HAEC. Direct cell contact with the metallic Zn surface resulted initially in cell attachment, but was quickly followed by cell death. After modification of the Zn surface using a layer of gelatin—intended to mimic a protein layer seen in vivo—the cells were able to attach and proliferate on the Zn surface. Further experiments demonstrated a Zn dose-dependent effect on cell spreading and migration, suggesting that both adhesion and cell mobility may be hindered by free Zn2+.

Long-term surveillance of zinc implant in murine artery: Surprisingly steady biocorrosion rate

“…Additionally, the Zn implants were observed to have penetration rates around the 20 µm/yr benchmark. The presence of viable cells around the wire at 20 months supports the recently reported biocompatibility of Zn [42,43]. The guidelines also state that full absorption of the implant should occur after 12–24 months [19], and the implants in this study showed only 60% CSA reduction at 20 months.…”

“…Alloying of Zn can improve its strength to the level of Fe and above [39–41], with elongation to failure remaining above values characteristic for pure Mg and Fe [19]. Studies so far on Zn as an experimental stent material have shown good biocompatibility and a rate of degradation between 10–20 µm/yr, which is similar to the 20 µm/yr benchmark value for an ideal bioabsorable material [42,43]. Zn implants were also found to remain intact in the murine arterial wall even after 6 months of residence, with the first 3–6 months after implantation being considered a critical period for coronary stent scaffolding [19].…”

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 .…”

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

“…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.…”