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Nickel in the exposed Implant Braze Joint

Biocompatibility, Risks and Next Steps

Summer 2023 Intern Research Project

Reya Mehta

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Introduction

The implant braze joint has nickel and titanium alloyed together (refer to part number 10132-01 rev A for the preform, 10136-01 rev A for the nickel-titanium material)
Nickel is known to be allergenic and not very biocompatible (Brown et al., 2020; Tsang et al., 2018).
Questions: What causes nickel-related adverse reactions? Is there pure nickel on the surface of the braze joint? How do we test that the implant is safe inside the human body?

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Biocompatibility of Nickel

Corrosion of nickel → allergic contact dermatitis.
Most common allergic responses to neuromodulatory implants with nickel are local dermatitis, erythema, and pruritus (Brown et al., 2020).
Prevalence of nickel allergy is rising as metals are more frequently used in everyday life

Ear piercings
Women are more likely to have a nickel allergy

Possible long-term risk as the allergy can, in rare cases, be induced by nickel exposure

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Nickel in Ni-Ti Brazing

After the brazing process, is there still free, unbonded nickel on the surface of the implant?
Ramp rates when brazing must be high to ensure that the nickel doesn’t melt before titanium – to prevent liquation (Panteli et al., 2012)
Jiang et al., 2005 had a similar preform to SPM – found no exposed free nickel

Carried out biocompatibility testing in sheep, results were positive

When I was researching, I asked Chula if he knew of any brazing methods to decrease the possibility of there being nickel ion release from the implant, and he explained that the ramp rate when brazing has to be really fast, because nickel has a lower melting point than titanium—the high ramp rate helps ensure that the nickel doesn’t melt before the titanium. So that’s one method of prevention.

This study from 2005 had a similar setup to SetPoint—brazing zirconia to a nickel-titanium alloy. They examined braze-joint cross-sections using SEM-EDS analysis, and their findings reported maximum concentrations of nickel around 30%, which is significantly below the nickel biocompatibility limit of 50%. They also did X-ray diffraction and electrochemical analysis, and there didn’t appear to be any free or elemental nickel on the surface after brazing, as it was all bonded to other elements. These are good indications for SetPoint, but we can’t be sure we’ll have the same results.

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Does the SPM Implant Braze Joint have exposed Nickel?

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Technical Considerations for Non-Clinical Assessment of Medical Devices Containing Nitinol

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FDA Guidance

https://www.fda.gov/news-events/fda-brief/fda-brief-fda-outlines-considerations-medical-devices-containing-metal-alloy-nitinol-part-ongoing

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-non-clinical-assessment-medical-devices-containing-nitinol

https://www.fda.gov/media/123272/download

https://www.astm.org/f3306-19.html

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ASTM standard

Pending Kevin purchase (and Sheri quote)

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Next Steps

Does SetPoint want to perform nickel ion leach testing?
If yes, officially for DVT/FDA submission? Unofficially for internal ER?
Pros: more data; ability to re-evaluate early if results are not ideal; ability to present to FDA if results are ideal
Cons: potentially expensive, time-consuming, and may require additional testing if results are unexpected
If yes, we should request quotes (for official short-term and long-term trials) from Element or Exponent