S1 - Determining the effect of alloying and surface treatment on the thrombogenicity of magnesium stents

Introduction: : Modern failures of stent intervention are due to the long-term presence of permanent metal devices. Many bioresorbable alternatives have arisen, with special interest on bioresorbable metals for their strong mechanical properties. Magnesium is a bioresorbable material with good strength and biocompatibility. Prior work in our lab indicates that magnesium exhibits incredibly low thrombogenicity, even delaying clotting time in vitro. Regardless, magnesium devices corrode too quickly for use as a cardiovascular stent. Researchers have used multiple approaches, such as alloying or surface treatments, to attempt to control magnesium corrosion. However, there is little understanding on the effects that these alterations will have on the hemocompatibility of the device when used as a stent material. This study examines the effects of magnesium alloying and surface treatments ex vivo and in vitro to further understand magnesium device design.

Materials and

Methods: : Magnesium materials with different alterations, namely alloying or surface treatments, were compared a clinical control, cobalt chromium (CoCr), in an ex-vivo non-human primate shunt loop. This shunt loop runs for 1 hr. and quantifies fibrin and platelet accumulation on the device, as well as downstream blood metrics for inflammation and thrombogenicity. Devices tested ex vivo were alloys ZX10, WE43, and AZ31. Surface treated WE22, another alloy, was also tested in the shunt loop with modifications such as anodization (WE22-A) and hydrofluorination (WE22-HF). Furthermore, in vitro characterization of the materials was performed using benchtop assays. These assays used human plasma and quantified FXIIa generation and fibrin clotting time, both aspects of the coagulation cascade.

Results, Conclusions, and Discussions:: Quantitative assessment of magnesium alloys showed no significant difference between the alloys, however, all had significantly less platelet accumulation than CoCr (Fig. 1). Surprisingly, both WE22-A and WE22-HF had significantly higher platelet accumulation than untreated WE22 (Fig. 2). Additionally, in vitro assays were performed using human plasma to investigate the cause of these results. Most alloyed materials performed similar to pure magnesium, with less FXIIa generation across all magnesium alloys compared to CoCr. A few alloys (WE43,AZ31) had significantly less FXIIa generation than pure magnesium. There were no significant differences between alloys in the fibrin clotting time assay. Furthermore, there were no significant differences found in the FXIIa generation or fibrin clotting time assay between WE22 and the surface treated conditions. All surface modified WE22 alloys, alongside unmodified WE22, had significantly lower FXIIa generation and higher fibrin clotting times than CoCr. These findings indicate magnesium alloys are good targets for alternatives to current clinical standards - alloying is an effective alteration for controlling corrosion without affecting thrombogenicity. Furthermore, the high level of thrombogenicity demonstrated ex vivo by surface modified WE22 indicates that surface modification could negatively effect the host response to the device. This research offers evidence for magnesium as a good choice for temporary stents while pointing researchers to more effective strategies to control corrosion without increasing thrombogenicity.

Acknowledgements and/or References (Optional):: We gratefully acknowledge financial support from NIH grants, R01HL144113, R01HL167442, and R01HL168696. Thanks to Fort Wayne Metals for drawing the wires. Finally, we acknowledge work performed by staff at the Oregon National Primate Research Center, supported by P51OD011092.