Biodegradable metals offer a promising means to ameliorate many of the long-term risks associated with vascular devices made of conventional biostable stent metals.While numerous biodegradable metal alloys have been d...Biodegradable metals offer a promising means to ameliorate many of the long-term risks associated with vascular devices made of conventional biostable stent metals.While numerous biodegradable metal alloys have been developed and characterized in animal models,knowledge of their blood reactivity and thrombogenicity remains unknown.Metal hemocompatibility is particularly valuable because current generation drug-eluting stents pose a significant long-term thrombosis risk.In this study,four pure metals,widely used as degradable base materials(Fe,Zn,Mg,and Mo),and three alloys commonly used in cardiovascular devices[NiTi,CoCr,and stainless steel(SS)]were evaluated.This work examined how each of these metals activate platelets,coagulation factors,and inflammation using in vitro hemocompatibility assays and a clinically relevant ex vivo non-human primate arteriovenous shunt model.Testing found that while all metals promoted a downstream activation of platelets and coagulation in flowing whole blood,platelet and fibrin attachment to Mg was markedly reduced.Additionally,Fe and Mo trended toward higher platelet attachment and contact pathway activation.Overall,the results suggest that Mg may delay clot initiation,but not eliminate clot formation,indicating the importance of understanding thrombosis in Mg alloys that are currently being developed for clinical use as biodegradable stents.展开更多
基金supported by National Institutes of Health(NIH)grants R01HL144113,R01HL101972,R01HL151367,R01HL168696,and R01HL146549The authors gratefully acknowledge the veterinary staff at the Oregon National Primate Research Center,supported by P51OD011092+1 种基金The authors also appreciate the technical consultations with Dr.Novella Keeling,Dr.Si-Han WangMr.Cole Baker.We thank Mr.Rick Mathews for his assistance in preparing this manuscript.SEM instrumentation was provided with the support of the OHSU Multiscale Microscopy Core.ICP-MS was completed at the OHSU Elemental Analysis Core,which is funded by grant S10OD028492 from the NIH.Schematic images were created with BioRender.com.
文摘Biodegradable metals offer a promising means to ameliorate many of the long-term risks associated with vascular devices made of conventional biostable stent metals.While numerous biodegradable metal alloys have been developed and characterized in animal models,knowledge of their blood reactivity and thrombogenicity remains unknown.Metal hemocompatibility is particularly valuable because current generation drug-eluting stents pose a significant long-term thrombosis risk.In this study,four pure metals,widely used as degradable base materials(Fe,Zn,Mg,and Mo),and three alloys commonly used in cardiovascular devices[NiTi,CoCr,and stainless steel(SS)]were evaluated.This work examined how each of these metals activate platelets,coagulation factors,and inflammation using in vitro hemocompatibility assays and a clinically relevant ex vivo non-human primate arteriovenous shunt model.Testing found that while all metals promoted a downstream activation of platelets and coagulation in flowing whole blood,platelet and fibrin attachment to Mg was markedly reduced.Additionally,Fe and Mo trended toward higher platelet attachment and contact pathway activation.Overall,the results suggest that Mg may delay clot initiation,but not eliminate clot formation,indicating the importance of understanding thrombosis in Mg alloys that are currently being developed for clinical use as biodegradable stents.
