Developing strategies to study exogenous biomaterial particles and ions within biological tissues

Authors: Alexander Paul Morrell (Aston University)
Co-authored by industrial partner: No

Type: Thesis

State: Published (Approved)
Published: April 2019
Diamond Proposal Number(s): 14113 , 16234

Abstract: The local and systemic dissemination of implant-related derivatives into the body is of great interest to human health. Biological exposures of metal micro/nano-particles, complexes and soluble ions, generated as a consequence of in-service degradation of metallic prosthetics, can result in severe adverse tissues reactions. However, individual reactions are highly variable and are not easily predicted, due to in part a lack of understanding of the properties of the metalstimuli which dictates cellular interactions and toxicity. However, interrogating ultra-dilute metals within fragile, hydrated biological tissues without influencing the native physical and/or chemical composition is challenging. Therefore, a drive for more advanced characterisation techniques of the exogenous metallic particles is required. Here, synchrotron-based X-ray fluorescence spectroscopy (XRF) and X-ray absorption near edge structure (XANES) were deployed to investigate the quantitative spatial distribution and local chemistry of implant-related metal particles within soft tissues. Analytical and experimental steps were outlined and improved when using XRF for greater accuracy in quantification. This included the implications of the matrix composition, the effects of saturation and how the instability in the flux and beam profile affected the measurement. Two post-analytical algorithms were generated to reduce the effects of image artefacts observed frequently in micro-focus XRF images. These methodological advances will have significant positive impact on quantitative XRF. Specifically, the quantitative XRF imaging displayed within this thesis, combined in a multi-institution research effort, influenced the future use of specific metallic implants. The chemistry of exogenous implant-related particles was also investigated, for the first time, using a XANES mapping approach. This enabled twodimensional chemical imaging at a high spatial resolution, allowing superior chemical discrimination of small, isolated, heterogenous features. This method highlighted the unreported variability in metal chemistry associated with orthopaedic implants, which may alter the perceived toxicity of implant derivatives. The results shown within this thesis outline the advantages of using a XANES mapping approach over conventional spectroscopy methods and should be considered when interrogating chemical species of metals in biological environments. Finally, a novel approach to co-locative analysis between exogenous metal particles and the underlying cellular content was developed using a lanthanide-antibody conjugate with XRF. This allowed simultaneous imaging of the native elemental distributions and biological epitopes. The development of this imaging modality is promising for understanding spatial relationships between such components. Collectively, advances within these interrogation methods applied to implant- related products will ultimately help our understanding of associated immunological responses and will generate more appropriate biological exposure models. Additionally, the advantages reported from the development of these techniques can be applied to an array of samples types in many areas of science.

Subject Areas: Biology and Bio-materials

Instruments: I18-Microfocus Spectroscopy

Other Facilities: ESRF

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