(H-305) Thrombosis on pure biodegradable metals for use in cardiovascular applications

Introduction: Stents are a prominent and critical component of care for cardiovascular patients. However, their permanence raises issues when reintervention is required. Biodegradable metals have great potential as stent materials, but little work has examined their thrombotic reactivity in whole blood. This work examined pure metal wires made of iron (Fe), zinc (Zn), molybdenum (Mo), and magnesium (Mg), as well as clinical, nondegradable alloys: stainless steel (SS), cobalt chromium (CoCr), and nickel titanium (NiTi). Wires were examined in an ex vivo non-human primate model of thrombosis to quantify platelet accumulation and activation, fibrin accumulation, macrophage activation, and overall thrombus quality.


Materials and Methods: Four pure metal (Fe, Zn, Mo, and Mg) and three alloy (SS, CoCr, and NiTi) wires were coiled around a 4mm rod and placed inside nonthrombogenic tubing. Coils were placed in a surgically implanted arteriovenous shunt in a juvenile, male baboon (papio anubus, 11.5kg) and exposed to flowing, whole blood without anticoagulant or antiplatelet therapies at 100mL/min for 1hr. The exteriorized shunt loop was placed over a gamma camera to dynamically quantify platelet accumulation on the coils with In-111 radiolabeled, autologous platelets. I-125 labeled fibrin was used to quantify endpoint fibrin accumulation. Blood was collected from the downstream boundary layer of the samples and processed to collect plasma. Blood samples were tested with fluorescence activated cell sorting (FACS). Plasma was used for biochemical assays and quantification of metal ions from the pure metal samples with inductively coupled plasma mass spectrometry (ICP-MS). Wires were fixed to image using scanning electron microscopy (SEM).


Results, Conclusions, and Discussions: All samples showed visible thrombus macroscopically with platelet and fibrin quantification being significantly lower for Mg, but largely unchanged for other groups (Fig. 1). SEM imaging showed platelets, fibrin, red blood cells, and neutrophils on all samples, with no visible differences in thrombus characteristics between the metal types. FACS showed no significant differences in platelet-leukocyte interactions, p-selectin, or lactadherin. ICP-MS showed no difference in ion concentration between the different metal types for any of the tested ions (Fe, Zn, Mo, Mg, Cu, Mn). These data suggest that no quantifiable degradation was seen during the short thrombosis testing. This was somewhat surprising for Mg, which is very reactive to aqueous solution and dissolves rapidly. This reactivity may explain the decreased platelet and fibrin accumulation seen on Mg compared to the other metals; however, the lack of differences seen with the FACS data indicate that the Mg stimulated platelets and leukocytes similarly to other metals. Overall, the observed thrombogenicity in all the samples suggested that none of the metals are inherently nonthrombogenic. Their clinical use will require the administration of antiplatelet or anticoagulant medications, which have an increased risk of bleeding. Future work will examine surface modifications of the biodegradable metals to improve their thrombogenic properties.


Acknowledgements: This work was supported by NIH grants R01HL130274, R01HL144113, R01HL101972, R01HL151367, and R01HL168696. We gratefully acknowledge the veterinary staff at the Oregon National Primate Research Center, supported by P51OD011092.