Metal particles of implants penetrate into the bone marrow

03-08-2020

The bone and bone marrow are exposed to metals from implants, scientists led by the Charité Medical University in Berlin (Germany) have found. Their results could ultimately lead to safer prosthesis. They are published today in Advanced Science.

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Metallic implants are frequently used in medicine to support and replace degenerated tissues. When an artificial joint is implanted in a patient, a foreign body reaction occurs, resulting in the formation of fibrous tissue around the implant.  Until now, it was assumed that this fibrotic membrane is prone to chemically isolate the implant from the surrounding tissue. This is one of the reasons why the scientific community has not yet examined whether the release of metallic implant material affects the surrounding bone marrow and bone tissue in humans.

Now researchers from the Charité Hospital in Berlin have assessed the exposure of metals released from artificial joints , like cobalt, titanium and chromium, in the adjacent bone and in the bone marrow. “In our previous study we found that cells from the bone where the implant was placed had lost capacity to form bone, and we were intrigued to find out why”, explains Janosch Schoon, first author of the paper and scientist at the Charité Medical University and now at the Medical University of Greifswald.

The comprehensive exploration of the topic required the combined expertise of different fields. The study is the result of a close collaboration between physicists, biologists, physicians, chemists and toxicologists.  The team hypothesized that metals like chromium and cobalt could accumulate in the body, and since it is well known that they can become toxic at certain levels, this could trigger bone loss. So they came to beamlines ID21 and ID16B at the ESRF to carry out X-ray fluorescence (XRF) with the aim to qualitatively and quantitatively analyse the metals and to identify their specific spatial distribution in bone and bone marrow on a micron- and nanoscale.

"The technical challenges for such experiments are many due to the complexity of the samples.  Synchrotron techniques allow us to image at the bone scale (millimeter) but also to locate nanometric metal particles, to detect the concentration of different metals and identify them, as well as their chemical state, which dictates their toxicity", explains Marine Cotte, scientist in charge of beamline ID21 and co-author of the study. She adds: "EBS and new instruments will allow us to be even more efficient in terms of speed, resolution and sensitivity". Schoon complements: “We were very lucky to be able to study the location, size and shape of these metals with the unique resolution that we get at the ESRF. It provided us with a broad picture of metal distribution in the bone and the bone marrow”.

Results were unexpected: “We were extremely surprised when we saw the extent of the metal exposure, especially titanium”, says Schoon.

The implications of these results are even more relevant given the organs studied: “It is important to note that the bone marrow is essential for hematopoiesis and the origin of all immune cells. The release of metallic implant materials can not only lead to the premature failure of the artificial joint, but also possibly have systemic consequences. Our results provide new insights into the toxicokinetics of metallic implant materials and help to better understand the development of implant-related pathologies.”, explains Sven Geissler, researcher at the Charité Medical University and senior author of the article.

“This study impressively proves the impact and importance of large scale research infrastructures such as the ESRF on society and on individual patients health. Now, there is not only translation from bench to bedside but also from beamline to bedside", explains Bernhard Hesse, CEO of Exployration and visiting scientist at the ESRF, and also co-author of the paper.

Paradigm shift

The study opens doors to new pre-clinical tests for endoprosthesis: “Our findings request a paradigm shift, and bone and bone marrow should be considered as relevant organs for pre-clinical testing and post-clinical risk-benefit evaluation of orthopedic biomaterials. Advanced models that mimic the organ function of human bone and bone marrow are needed for extending pre-clinical assessments. Ultimately, we hope to keep implant safety at the highest possible level”, concludes Schoon. 

The scientists will now continue their research in implants that have been placed for different lengths of time in different patients. “We know that in some patients the implants fail very early, while in others problems occur much later and yet others never have an issue. We would like to be able to predict which implant material is the most reasonable choice for which patient”, concludes Geissler.

REFERENCE:

Schoon, J., et al, Advanced Science, 3 August 2020. DOI: 10.1002/advs.202000412.  

Text by Montserrat Capellas Espuny

 

 

Top image: An artist's impression of the bone marrow being studied at the ESRF. Credits: J. Schoon.