163HIGHLIGHTS 2020

NEW INSIGHTS INTO METAL DISTRIBUTION IN PERI- IMPLANT BONE AND BONE MARROW Joint replacement surgery is a successful procedure but in some cases, metallic implants loosen over time. Micro- and nano-resolved synchrotron XRF analyses of surrounding bone and bone marrow show specific accumulation of metals released from implant alloys. Local toxicokinetics of cobalt, chromium and titanium were identified, helping to explain implant loosening.

Fig. 141: Representative experimental strategy. a) Red areas depicted in preoperative X-ray radiographies indicate regions from which samples were harvested near to arthroplasty implants and from a patient without implant. b) A harvested specimen and H&E staining of peri-implant cancellous bone including bone marrow. c) Corresponding qualitative micro-XRF maps: Full image (30 µm spatial resolution), yellow rectangle (10 µm spatial resolution), pink rectangle (2 µm spatial resolution). d) Quantitative

heat-map of Cr weight fractions in the 2 µm resolved micro-XRF map and an averaged XRF-spectrum of marrow structures indicating predominant exposure to Co and Cr. e) Qualitative nano-XRF map with a spatial resolution of 60 nm.

Adverse effects of exposure to implant-derived metals, including aseptic local inflammation and resulting bone loss, have been shown to occur behind an insulating peri-implant membrane in the peri-implant bone. However, the extent of exposure and the distribution patterns of metals in bone and bone marrow remained unknown.

Spatially micro- and nano-resolved multi-metal quantification was performed by synchrotron-based X-ray fluorescence (XRF) imaging of peri-implant cancellous bone and intertrabecular bone marrow from patients with arthroplasty implants. The XRF-scanning strategy (Figure 141) was based on large- fields-of-view micro-XRF analyses performed at beamline ID21. Samples were then transferred to the nanoprobe beamline ID16B for XRF scanning at 60 nm resolution at 25.6 keV.

The XRF-maps indicated significant exposure to micro- and nano-sized cobalt, chromium, and titanium. In peri-implant bone marrow, particulate cobalt is exclusively co-localised with chromium, and non-particulate chromium accumulates in the bone marrow matrix. Particles consisting of cobalt and chromium contain less cobalt than bulk alloy, which indicates a pronounced dissolution capacity. The distinct matrix accumulation of chromium, which could also be reproduced in a human 3D in-vitro model, and the dissolution capacity of cobalt, explains higher cobalt than chromium levels in the blood circulation of patients with failed arthroplasty implants. XRF-maps of

trabecular bone indicated integration of cobalt and chromium but not titanium.

The data reveal toxicokinetic mechanisms and a novel view on the long-term effects of degradation products from metal-based biomaterials in the body. These findings merit