Clinical importance of biocorrosion of metal implants - experimentation and modeling
Date Issued
March 9, 2022
Abstract
Medical device materials contain chemicals that pose toxicological problems if released in
sufficient quantities in the body. Toxicological risk assessment and prevention by manufacturers
include metal surface treatments, in vitro extraction testing and animal experiments to minimize the
potential for patients to be exposed to chemicals that may possibly leach out of device materials.
Stent retrieval studies by us and others [1.2.3] have shown significant corrosion and leaching of
device materials into the body with significant concern by the FDA in numerous recent reports [3,4].
To investigate the peri-implant tissue response to stent biocorrosion, custom made self-expanding
nitinol stents (0.7 x 3.3 mm), were implanted in the common carotid artery of male CD1 mice (Project
license: CY/EXP/PR.L9/2019). Non-corroded (electropolished) and corroded (heat treated) stents
were pre- and post-implantation examined using SEM and also evaluated for Ni ion release
(quantified via ICP-MS) in a 60-day immersion test in PBS. Sham-stented samples were also prepared
to control for any non-stent related inflammatory effects such as endothelial layer damage caused
during catheter guidance. Mice were euthanized under anesthesia at 4 and 8 weeks after surgery and
harvested tissue samples were perfusion fixed in situ with 4% PFA for histological analysis which
included stent-tissue interaction, thrombus formation, inflammation, and the presence of neointima.
A separate group of operated mice was also prepared for nickel ion quantification in peri-implant
tissue (dissolved in NaOH and analyzed via ICP-MS). Right before euthanasia, whole blood samples
were collected, in citrate prefilled syringes using the cardiac puncture technique, for hematological
analysis. Our results indicate that stent surface condition and implantation time affect the
development and extent of neointima. The hematological and histological data revealed a significant
increase in inflammatory cells, thrombus formation and mature neointima in corroded stented
aortas with respect to the electropolished stented aortas. Elevated metal particle contamination,
prompted by corroded stents, triggers an inflammatory response. Further studies are warranted to
systematically characterize this mechanism that may lead to the development of in-stent restenosis.
sufficient quantities in the body. Toxicological risk assessment and prevention by manufacturers
include metal surface treatments, in vitro extraction testing and animal experiments to minimize the
potential for patients to be exposed to chemicals that may possibly leach out of device materials.
Stent retrieval studies by us and others [1.2.3] have shown significant corrosion and leaching of
device materials into the body with significant concern by the FDA in numerous recent reports [3,4].
To investigate the peri-implant tissue response to stent biocorrosion, custom made self-expanding
nitinol stents (0.7 x 3.3 mm), were implanted in the common carotid artery of male CD1 mice (Project
license: CY/EXP/PR.L9/2019). Non-corroded (electropolished) and corroded (heat treated) stents
were pre- and post-implantation examined using SEM and also evaluated for Ni ion release
(quantified via ICP-MS) in a 60-day immersion test in PBS. Sham-stented samples were also prepared
to control for any non-stent related inflammatory effects such as endothelial layer damage caused
during catheter guidance. Mice were euthanized under anesthesia at 4 and 8 weeks after surgery and
harvested tissue samples were perfusion fixed in situ with 4% PFA for histological analysis which
included stent-tissue interaction, thrombus formation, inflammation, and the presence of neointima.
A separate group of operated mice was also prepared for nickel ion quantification in peri-implant
tissue (dissolved in NaOH and analyzed via ICP-MS). Right before euthanasia, whole blood samples
were collected, in citrate prefilled syringes using the cardiac puncture technique, for hematological
analysis. Our results indicate that stent surface condition and implantation time affect the
development and extent of neointima. The hematological and histological data revealed a significant
increase in inflammatory cells, thrombus formation and mature neointima in corroded stented
aortas with respect to the electropolished stented aortas. Elevated metal particle contamination,
prompted by corroded stents, triggers an inflammatory response. Further studies are warranted to
systematically characterize this mechanism that may lead to the development of in-stent restenosis.
Subjects
File(s)![Thumbnail Image]()
Name
BraMat2022 abstract.pdf
Size
225.26 KB
Format
Adobe PDF
Checksum (MD5)
915ac61493ed9edc94e54a6646dfe714