D17 - Understanding the host response to Zn-alloy wires for use in bioresorbable cardiovascular stents

Introduction: : Biodegradable cardiovascular stents offer a promising solution for treating vascular occlusion with a temporary device, allowing for potential reintervention and reducing the need for long-term antithrombotic therapies. However, zinc-based implants often trigger a chronic inflammatory response, albeit typically mild. Developing zinc-based stents with thinner struts could reduce toxicity and improve delivery of the stents. This study evaluates the in vitro, ex vivo, and in vivo responses to novel Zn alloys with reduced dimensions.

Materials and

Methods: : Zn alloys with a stainless steel (SS) control were tested in vitro using human blood plasma to examine coagulation FXII activation and fibrin generation. Zn alloy (AMZ, ACMZ, CMM) and SS coils were also tested in an ex vivo non-human primate model using whole, flowing blood without anticlotting medication for 1hr.1 Blood metrics for inflammation, platelet activation, and thrombosis were measured downstream of the alloy wires. Separately, the zinc-alloy wires were implanted into rat arteries to investigate the biological responses over a period of 3mths by histological staining.

Results, Conclusions, and Discussions:: Quantitative FXII activation and fibrin generation results showed no significant results from the human plasma. Similarly, the flowing ex vivo blood tests showed similar platelet and fibrin accumulation on the metals (Fig. 1). Qualitatively, all the wires showed thrombus with fibrin, red blood cells, platelets, and immune cells from scanning electron microscope visualization. Implants in rat arteries experienced healthy tissue growth with mild to moderate levels of chronic inflammation, consistent with prior reports of zinc implants into arterial tissue. The area of neointimal tissue (NA) formed around arterial implants was significantly reduced in 120 vs. 250 um diameter wires (Fig. 2). The lack of significant differences between SS and Zn alloys when tested for thrombogenicity suggests that the experimental alloys will perform similarly to current clinical devices when used for cardiovascular applications. The reduction in NA in the thin wire implants suggest that reduced dimensions favor the biocompatibility of zinc-alloys.

Acknowledgements and/or References (Optional):: Fort Wayne metals drew the metal wires. This project was supported by NIH grants, R01HL144113, R01HL167442, and R01HL168696. We gratefully acknowledge the veterinary staff at the Oregon National Primate Research Center, supported by P51OD011092.