Predicting patient exposure to nickel released from cardiovascular devices using multi-scale modeling

Area of Science:

• Biomedical Engineering
• Materials Science
• Toxicology

Background:

• Cardiovascular devices often contain nickel alloys, posing potential health risks if nickel ions are released.
• In-vivo nickel release and biodistribution from implanted devices are not well understood, hindering risk assessment.
• In-vitro tests for metal ion release may not accurately represent clinical environments, creating uncertainty in patient risk evaluation.

Purpose of the Study:

• To develop and validate a multi-scale biokinetic model to predict nickel ion concentrations in patients with cardiovascular devices.
• To link nickel release from devices to levels in peri-implant tissue, serum, and urine.
• To improve the evaluation of patient risk from nickel in medical implants.

Main Methods:

• Developed a multi-scale (material, tissue, system) biokinetic model.
• Parameterized the model for nitinol septal occluders using in-vitro release, ex-vivo uptake, and in-vivo/clinical data.
• Validated the model by comparing predictions with animal model tissue concentrations and patient serum/urine data.

Main Results:

• The model accurately predicted nickel concentrations in peri-implant tissue (animal model) and in serum and urine (patient data).
• Predicted local and systemic nickel exposure from nitinol devices across various manufacturing processes.
• Established relationships between nickel release rate and exposure, suggesting safe limits for device manufacturing.

Conclusions:

• The validated biokinetic model provides useful insights for establishing nickel exposure limits and interpreting biomonitoring data.
• The model can help assess patient risk from nickel in cardiovascular devices.
• This approach can be extended to other metal ions and biomedical products.