Improved metallic GLASses for Small Implants through X-ray and biological characterisation of corrosion products

Periodic Reporting for period 1 - GLASSIX (Improved metallic GLASses for Small Implants through X-ray and biological characterisation of corrosion products)

Berichtszeitraum: 2015-11-01 bis 2017-10-31

Millions of people around the world enjoy healthier lives due to the use of implants (dental implants, hip replacements etc.). Small metallic implants, such as those used in dentistry, craniofacial applications, bone-anchored hearing aids and some orthopaedic applications (spinal/finger joints) are particularly challenging as miniaturisation reduces the surface area available for bone ingrowth. Small devices are associated with stress concentration and a susceptibility to chronic local inflammation which can lead to progressive bone loss in up to 56% of devices. This can cause pain, and the implant may loosen and fail. The increased strength of metallic glasses would be ideally suited to such applications if they can be produced with suitable corrosion resistance.
Ti is protected from corrosion by a thin film of TiO2 and conventional “biocompatibility” testing focuses on the interactions between this surface and human tissue. However, most Ti implant failures occur through “mechanically-assisted crevice corrosion” (MACC), which takes place when a Ti implant is in tight contact with another solid surface such as metal, cement or bone. Slight vibrations abrade the oxide film, leading to Ti dissolution generating a highly acidic solution in the gap that can leach into the adjacent tissue causing pain and tissue damage. Solid corrosion product particles and metal fragments can also be released into the tissue, causing adverse physiological reactions. It is therefore clear that the improved mechanical properties and corrosion resistance of Ti metallic glasses offers great promise for small implants. However, their corrosion products are completely unknown, and they have never been subjected to MACC tests.
The main objective was to evaluate the local corrosion behaviour and MACC of new Ti-based bulk metallic glasses with focus on characterisation of corrosion products with methods including in situ synchrotron X-rays. Another objective was to determine the biological compatibility of the new alloys including corrosion products simulants. Finally another objective was to work with an industrial partner to identify the feasibility of translating one or more metallic glasses into clinical practice.
A series of Ti-based bulk metallic glasses were found to have good corrosion resistance in simulated body conditions. Using in situ synchrotron X-ray diffraction it was found that a Ti-based bulk metallic glass generates a series of corrosion products including metallic nanoparticles. In vitro biological testing with structural and immune cell lines revealed that the different corrosion products elicit significantly different cellular behaviours highlighting the need to identify accurately the nature of the corrosion products as part of routine biocompatibility testing. Initial MACC experiments indicate that certain Ti-based bulk metallic glasses might have significantly higher MACC resistance than current implant Ti alloys. A certain Ti-based bulk metallic glass was found to have regulatory and manufacturing feasibility and further detailed characterisation is under way to determine the best indication for its use.

Corrosion products in artificial pits on a Ti-based bulk metallic glass and on pure Zr were characterised in situ using X-ray diffraction, X-ray absorption near edge structure and X-ray fluorescence mapping at the Diamond Light Source synchrotron (UK). It was found that Zr may generate micrometre-sized Zr fragments in artificial pits indicating such fragments may be formed by Zr containing implant alloys. The metallic glass may generate metallic Pd nanoparticles, PdCl2, CuCl and other minority compounds. The formation of Zr fragments and Pd nanoparticles was confirmed by ex situ transmission electron microscopy investigations.
The biological compatibilities of the Ti-based bulk metallic glass were assessed with structural cells and immune cell lines. Different corrosion products elicited significantly different cellular behaviours in in-vitro assays. For examples, CuCl significantly reduced reactive oxygen species formation in neutrophils in a dose dependent manner whereas PdCl2 and zirconyl octahydrate were stimulatory. In contrast zirconyl octahydrate resulted in a significant reduction in neutrophil extracellular trap formation. The findings highlight the need to identify accurately the nature of corrosion products as part of routine biocompatibility testing.
Mechanically-assisted crevice corrosion (MACC) tests have been carried out with a custom MACC device on three metallic glasses. The sample geometry for MACC had to be modified in order to allow testing of smaller samples made of metallic glass. Promising results were obtained on the metallic glasses, which appear to have a MACC resistance much higher than that of conventional Ti.
We have worked closely with a major European dental implants manufacturer throughout the project. This successfully manufactured implants in industrial conditions with their standard geometry from Ti-based bulk metallic glass and performed an extensive series of standard testing regarding mechanical, corrosion and biological performance as required for implant validation according to current regulation. Important technical milestones have been reached and this alloy was found to have both regulatory and manufacturing feasibility. Materials performances are now being evaluated more closely to determine the best indication for its use.
Results in this project are/will be presented in 6 scientific articles in peer-reviewed journals (one is published, three are will be submitted shortly, and two in preparation) and 6 talks at international conferences.

The in situ X-ray diffraction investigations have revealed that it is possible to generate metal particles by corrosion in artificial pits in conditions relevant for implant service from Zr and a Ti-based bulk metallic glass. Biological tests under way at the moment will reveal the biocompatibility of those particles. This methodology of evaluating the biocompatibility of new alloys products goes beyond the current standard which involves testing only the alloy surface and corrosion products generated on flat surfaces (ISO 10993). The results in this project are expected to create awareness in the biomaterials development community of the need for such an improved methodology leading eventually to a modification of the biological evaluation standards.
To our knowledge, this is the first investigation into the applicability of bulk metallic glasses for dental implants in the European space. They were found to have both regulatory and manufacturing feasibility and following additional more detailed investigations these will very likely be used for certain components in mini-invasive implant systems.

In situ X-ray diffraction experiment on artificial pit on metallic glass.

Periodic Reporting for period 1 - GLASSIX (Improved metallic GLASses for Small Implants through X-ray and biological characterisation of corrosion products)

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