RESUMO
The relationship between reactive oxygen and nitrogen species (ROS-RNS) secretion and the concomitant biocorrosion of degradable magnesium (Mg) materials is poorly understood. We found that Mg foils implanted short term in vivo (24 h) displayed large amounts of proinflammatory F4/80+/iNOS + macrophages at the interface. We sought to investigate the interplay between biodegrading Mg materials (98.6% Mg, AZ31 & AZ61) and macrophages (RAW 264.7) stimulated with lipopolysaccharide (RAW 264.7LPS) to induce ROS-RNS secretion. To test how these proinflammatory ROS-RNS secreting cells interact with Mg corrosion in vitro, Mg and AZ61 discs were suspended approximately 2 mm above a monolayer of RAW 264.7 cells, either with or without LPS. The surfaces of both materials showed acute (24 h) changes when incubated in the proinflammatory RAW 264.7LPS environment. Mg discs incubated with RAW 264.7LPS macrophages showed greater corrosion pitting, while AZ61 showed morphological and elemental bulk product changes via scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX). X-ray photoelectron spectroscopy (XPS) analysis showed a reduction in the Ca/P ratio of the surface products for AZ61 disc incubated with RAW 264.7LPS, but not the Mg discs. Moreover, RAW 264.7LPS macrophages were found to be more viable in the acute biodegradative environment generated by Mg materials, as demonstrated by calcein-AM and cleaved (active) caspase-3 staining (CC3). LPS stimulation caused an increase in ROS-RNS, and a decrease in antioxidant peroxidase activity. Mg and AZ61 were found to change this ROS-RNS balance, independently of physiological antioxidant mechanisms. The findings highlight the complexity of the cellular driven acute inflammatory responses to different biodegradable Mg, and how it can potentially affect performance of these materials.
RESUMO
Biodegradable stents have tremendous theoretical potential as an alternative to bare metal stents and drug-eluting stents for the treatment of obstructive coronary artery disease. Any bioresorbable or biodegradable scaffold material needs to possess optimal mechanical properties and uniform degradation behavior that avoids local and systemic toxicity. Recently, molybdenum (Mo) has been investigated as a potential novel biodegradable material for this purpose. With its proven moderate degradation rate and excellent mechanical properties, Mo may represent an ideal source material for clinical cardiac and vascular applications. The present study was performed to evaluate the mechanical performance of metallic Mo in vitro and the biodegradation properties in vivo. The results demonstrated favorable mechanical behavior and a uniform degradation profile as desired for a new generation ultra-thin degradable endovascular stent material. Moreover, Mo implants in mouse arteries avoided the typical cellular response that contributes to restenosis. There was minimal neointimal hyperplasia over 6 months, an absence of excessive smooth muscle cell (SMC) proliferation or inflammation near the implant, and avoidance of significant harm to regenerating endothelial cells (EC). Qualitative inspection of kidney sections showed a potentially pathological remodeling of kidney Bowman's capsule and glomeruli, indicative of impaired filtering function and development of kidney disease, although quantifications of these morphological changes were not statistically significant. Together, the results suggest that the products of Mo corrosion may exert beneficial or inert effects on the activities of inflammatory and arterial cells, while exerting potentially toxic effects in the kidneys that warrant further investigation.