Flow diverting stents are braided,metallic endoluminal devices widely used to treat intracranial aneurysms.Bioresorbable flow diverters(BRFDs)are gaining traction as the next generation of flow diverter technology.BRF...Flow diverting stents are braided,metallic endoluminal devices widely used to treat intracranial aneurysms.Bioresorbable flow diverters(BRFDs)are gaining traction as the next generation of flow diverter technology.BRFDs aim to occlude and heal the aneurysm before safely dissolving into the body,mitigating or eliminating complications associated with the permanent presence of conventional flow diverters such as thromboembolism and stenosis.Additional putative advantages of a BRFD include a reduction in metal induced medical imaging artifacts,a restoration of physiological vasoreactivity,and allowing physicians to re-access the aneurysm if an additional procedure is required.In this current study,iron-manganese-nitrogen(FeMnN)alloy BRFDs and permanent control FDs composed of an industry standard Cobalt-Nickel-Chromium alloy were deployed in the rabbit aorta.MicroCT and SEM corrosion analysis determined the FeMnN wire volumes and cross-sectional areas had reduced approximately 85%and 95%after 3-and 6-months implantation duration,respectively.Histo-logical analysis demonstrated the BRFDs exhibited suitable biocompatibility,with no cases of in-stent throm-bosis,clinically significant stenosis,or adverse tissue responses observed.Immunohistochemistry revealed the neointimas surrounding the BRFDs featured a confluent endothelium covering several layers of smooth muscle cells,with macrophages adjacent to the device wires.The macrophages were able to penetrate the corrosion product and were observed transporting corrosion products away from the implant site.This current work provides primary in vivo corrosion and biocompatibility data to the field for FeMn alloys,which we feel will stimulate and inform the design of next-generation bioresorbable endovascular devices.展开更多
Flow diverter devices are small stents used to divert blood flow away from aneurysms in the brain,stagnating flow and inducing intra-aneurysmal thrombosis which in time will prevent aneurysm rupture.Current devices ar...Flow diverter devices are small stents used to divert blood flow away from aneurysms in the brain,stagnating flow and inducing intra-aneurysmal thrombosis which in time will prevent aneurysm rupture.Current devices are formed from thin(~25μm)wires which will remain in place long after the aneurysm has been mitigated.As their continued presence could lead to secondary complications,an absorbable flow diverter which dissolves into the body after aneurysm occlusion is desirable.The absorbable metals investigated to date struggle to achieve the necessary combination of strength,elasticity,corrosion rate,fragmentation resistance,radiopacity,and biocompatibility.This work proposes and investigates a new composite wire concept combining absorbable iron alloy(FeMnN)shells with one or more pure molybdenum(Mo)cores.Various wire configurations are produced and drawn to 25–250μm wires.Tensile testing revealed high and tunable mechanical properties on par with existing flow diverter materials.In vitro degradation testing of 100μm wire in DMEM to 7 days indicated progressive corrosion and cracking of the FeMnN shell but not of the Mo,confirming the cathodic protection of the Mo by the FeMnN and thus mitigation of premature fragmentation risk.In vivo implantation and subsequentμCT of the same wires in mouse aortas to 6 months showed meaningful corrosion had begun in the FeMnN shell but not yet in the Mo filament cores.In total,these results indicate that these composites may offer an ideal combination of properties for absorbable flow diverters.展开更多
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 sca...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.展开更多
基金National Institutes of Health grant#R01 NS076491supported by American Heart Association grant 23PRE1012781.
文摘Flow diverting stents are braided,metallic endoluminal devices widely used to treat intracranial aneurysms.Bioresorbable flow diverters(BRFDs)are gaining traction as the next generation of flow diverter technology.BRFDs aim to occlude and heal the aneurysm before safely dissolving into the body,mitigating or eliminating complications associated with the permanent presence of conventional flow diverters such as thromboembolism and stenosis.Additional putative advantages of a BRFD include a reduction in metal induced medical imaging artifacts,a restoration of physiological vasoreactivity,and allowing physicians to re-access the aneurysm if an additional procedure is required.In this current study,iron-manganese-nitrogen(FeMnN)alloy BRFDs and permanent control FDs composed of an industry standard Cobalt-Nickel-Chromium alloy were deployed in the rabbit aorta.MicroCT and SEM corrosion analysis determined the FeMnN wire volumes and cross-sectional areas had reduced approximately 85%and 95%after 3-and 6-months implantation duration,respectively.Histo-logical analysis demonstrated the BRFDs exhibited suitable biocompatibility,with no cases of in-stent throm-bosis,clinically significant stenosis,or adverse tissue responses observed.Immunohistochemistry revealed the neointimas surrounding the BRFDs featured a confluent endothelium covering several layers of smooth muscle cells,with macrophages adjacent to the device wires.The macrophages were able to penetrate the corrosion product and were observed transporting corrosion products away from the implant site.This current work provides primary in vivo corrosion and biocompatibility data to the field for FeMn alloys,which we feel will stimulate and inform the design of next-generation bioresorbable endovascular devices.
基金support of Carlo Wolf(School of Mechanical Engineering,University of Applied Sciences Stralsund)for support with the CT analysis and metallographic preparation,Aubrey L.Ehle(Indiana University School of Medicine)for support with the radiopacity assessment,and Amani Gillette(Morgridge Institute for Research)for support with the cytotoxicity analysis.Parts of this study were completed using Michigan Technological University’s Applied Chemical and Morphological Analysis Laboratory.RG and NP were partially supported by NIH R15HL167221AO is supported by American Heart Association grant 23PRE1012781.
文摘Flow diverter devices are small stents used to divert blood flow away from aneurysms in the brain,stagnating flow and inducing intra-aneurysmal thrombosis which in time will prevent aneurysm rupture.Current devices are formed from thin(~25μm)wires which will remain in place long after the aneurysm has been mitigated.As their continued presence could lead to secondary complications,an absorbable flow diverter which dissolves into the body after aneurysm occlusion is desirable.The absorbable metals investigated to date struggle to achieve the necessary combination of strength,elasticity,corrosion rate,fragmentation resistance,radiopacity,and biocompatibility.This work proposes and investigates a new composite wire concept combining absorbable iron alloy(FeMnN)shells with one or more pure molybdenum(Mo)cores.Various wire configurations are produced and drawn to 25–250μm wires.Tensile testing revealed high and tunable mechanical properties on par with existing flow diverter materials.In vitro degradation testing of 100μm wire in DMEM to 7 days indicated progressive corrosion and cracking of the FeMnN shell but not of the Mo,confirming the cathodic protection of the Mo by the FeMnN and thus mitigation of premature fragmentation risk.In vivo implantation and subsequentμCT of the same wires in mouse aortas to 6 months showed meaningful corrosion had begun in the FeMnN shell but not yet in the Mo filament cores.In total,these results indicate that these composites may offer an ideal combination of properties for absorbable flow diverters.
基金U.S.National Institute of Health-National Heart,Lung,and Blood Institute grants R15HL147299 and R01HL144739 are acknowledged for funding this work.
文摘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.
