Zn2+-dependent suppression of vascular smooth muscle intimal hyperplasia from biodegradable zinc implants

Guillory, Roger J.; Kolesar, Timothy M.; Oliver, Alexander A.; Stuart, Jeffrey A.; Bocks, Martin L.; Drelich, Jaroslaw; Goldman, Jeremy

doi:10.1016/j.msec.2020.110826

Cited by 23 publications

(23 citation statements)

References 24 publications

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“…This was not a surprise as earlier studies from our group and others have demonstrated a VSMC suppressive property for pure Zn implants. Following up on these early observations, we have recently reported that ionic Zn suppresses VSMC NI hyperplasia by activating caspase-3-dependent apoptosis signaling pathways . The present report demonstrates that the VSMC suppressive property of pure Zn arterial implants is retained following alloying to improve mechanical properties.…”

Section: Discussionsupporting

confidence: 68%

“…Following up on these early observations, we have recently reported that ionic Zn suppresses VSMC NI hyperplasia by activating caspase-3-dependent apoptosis signaling pathways. 40 The present report demonstrates that the VSMC suppressive property of pure Zn arterial implants is retained following alloying to improve mechanical properties. This VSMC suppressive property is expected to decrease NI size and therefore improve the biocompatibility of Zn-based BRS materials.…”

Section: Discussionmentioning

confidence: 53%

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Analysis of Vascular Inflammation against Bioresorbable Zn–Ag-Based Alloys

Oliver

Guillory

Flom

et al. 2020

ACS Appl. Bio Mater.

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Zinc (Zn) has emerged as a promising bioresorbable stent material because of its satisfactory corrosion behavior and excellent biocompatibility. However, for load-bearing implant applications, alloying is required to boost its mechanical properties as pure Zn exhibits poor strength. Unfortunately, an increase in inflammation relative to pure Zn is a commonly observed side effect of Zn alloys. Consequently, the development of a Zn-based alloy that can simultaneously feature improved mechanical properties and suppress inflammatory responses is a big challenge. Here, a bioresorbable, biocompatible Zn–Ag-based quinary alloy was comprehensively evaluated in vivo, in comparison to reference materials. The inflammatory and smooth muscle cellular response was characterized and correlated to metrics of neointimal (NI) growth. We found that implantation of the quinary alloy was associated with significantly improved inflammatory activities relative to the reference materials. Additionally, we found that inflammation, but not smooth muscle cell hyperplasia, significantly correlates to NI growth for Zn alloys. The results suggest that inflammation is the main driver of NI growth for Zn-based alloys and that the quinary Zn–Ag–Mn–Zr–Cu alloy may impart inflammation-resistance properties to arterial implants.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 53%

Analysis of Vascular Inflammation against Bioresorbable Zn–Ag-Based Alloys

Oliver

Guillory

Flom

et al. 2020

ACS Appl. Bio Mater.

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“…To examine this effect further, an ex vivo arterial culture study washed tissue slices prepared from the thoracic aorta of rats with 0.5–1.5 mM Zn-acetate to simulate zinc corrosion products. Suppression of caspase-8 and -9 activity was observed at high concentrations, as well as a dose-dependent activation of caspase-3 activity [17] . These results are consistent with studies that have demonstrated decreased cell viability in response to zinc exposure [ 6 , 10 ].…”

Section: Introductionmentioning

confidence: 88%

“…Consistent with this, a similar gradient was observed with pure zinc stent implants in rabbit abdominal aorta [16] . These results suggest that zinc corrosion products released from metal implants suppress smooth muscle cell hyperproliferation but do not affect endothelization or smooth muscle cells in the medial layer of the aorta [ 15 , 17 ]. To examine this effect further, an ex vivo arterial culture study washed tissue slices prepared from the thoracic aorta of rats with 0.5–1.5 mM Zn-acetate to simulate zinc corrosion products.…”

Section: Introductionmentioning

confidence: 99%

Bioabsorbable metal zinc differentially affects mitochondria in vascular endothelial and smooth muscle cells

Bagshaw

Moradi

Moffatt

et al. 2021

Biomaterials and Biosystems

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“…However, there are still some issues with zinc and its alloys. One of the drawbacks is that Zn and its alloys would induce more Zn ions, which are reported to be cytotoxic to cells [12]. Although zinc alloys showed good biocompatibility in in vivo assays, previous studies showed that cells exposed directly to zinc and its alloys would hardly survive [13].…”

Section: Introductionmentioning

confidence: 99%

Preliminary Investigation on Degradation Behavior and Cytocompatibility of Ca-P-Sr Coated Pure Zinc

Xie

Tang

et al. 2021

Coatings

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Zinc and its alloys show a good application prospect as a new biodegradable material. However, one of the drawbacks is that Zn and its alloys would induce the release of more Zn ions, which are reported to be cytotoxic to cells. In this study, a Ca-P-Sr bioactive coating was prepared on the surface of pure zinc by the hydrothermal method to address this issue. The morphology, thickness, and composition were characterized, and the effects of the coating on the degradation, cell viability, and ALP staining were investigated. The results demonstrated that the degradation rate of pure zinc was reduced, while the cytocompatibility was significantly improved after pure zinc was treated with Ca-P-Sr coating. It is considered that the Ca-P-Sr bioactive coating prepared by the hydrothermal method has promising application in the clinic.

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Zn2+-dependent suppression of vascular smooth muscle intimal hyperplasia from biodegradable zinc implants

Cited by 23 publications

References 24 publications

Analysis of Vascular Inflammation against Bioresorbable Zn–Ag-Based Alloys

Analysis of Vascular Inflammation against Bioresorbable Zn–Ag-Based Alloys

Bioabsorbable metal zinc differentially affects mitochondria in vascular endothelial and smooth muscle cells

Preliminary Investigation on Degradation Behavior and Cytocompatibility of Ca-P-Sr Coated Pure Zinc

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