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Instruments / Technical Area	Publication Details	Published	Actions
I08-Scanning X-ray Microscopy beamline (SXM)	A comparative study on the physicochemical characteristics of nanoparticles released in vivo from CoCrMo tapers and cement–stem interfaces of total hip replacements Alina M. Crainic , Mauro Callisti , Arjen Van Veelen , Agnes Michalik , James A. Milton , Martin R. Palmer , Richard B. Cook Journal Of Biomedical Materials Research Part B: Applied Biomaterials 41 DOI: 10.1002/jbm.b.34667 Diamond Proposal Number(s): [17801, 17203] Show Abstract ▼ Abstract: The good biocompatibility and corrosion resistance of the bulk CoCrMo alloy has resulted in it being used in the manufacture of implants and load bearing medical devices. These devices, however, can release wear and corrosion products which differ from the composition of the bulk CoCrMo alloy. The physicochemical characteristics of the particles and the associated in vivo reactivity are dictated by the wear mechanisms and electrochemical conditions at the sites of material loss. Debris released from CoCrMo hip bearings, taper junctions, or cement–stem interfaces can, therefore, have different chemical and morphological characteristics, which provide them with different in vivo toxicities. Here, we propose to assess and compare the characteristics of the particles released in vivo from CoCrMo tapers and cement–stem interfaces which have received less attention compared to debris originating from the hip bearings. The study uses state‐of‐art characterization techniques to provide a detailed understanding of the size, morphology, composition, and chemistry of the particles liberated from the wear and corrosion flakes from revised hip replacements, with an enzymatic treatment. The phase analyses identified Cr2O3 nanoparticles released from tapers and cement–stem interfaces, whose composition did not vary with origin or particle morphology. The size distributions showed significantly smaller particles were released from the stems, compared to the particles originating from the corresponding tapers. The investigation demonstrates that the tribocorrosive processes occurring at the taper and stem interfaces both result in Cr2O3 nanoparticle formation.	Jun 2020
I08-Scanning X-ray Microscopy beamline (SXM)	Upregulation of epithelial metallothioneins by metal-rich ultrafine particulate matter from an underground railway Matthew Loxham , Jeongmin Woo , Akul Singhania , Natalie P. Smithers , Alison Yeomans , Graham Packham , Alina M. Crainic , Richard B. Cook , Flemming R. Cassee , Christopher H. Woelk , Donna E. Davies Metallomics 122 DOI: 10.1039/D0MT00014K Diamond Proposal Number(s): [17801] Open Access Show Abstract ▼ Abstract: Airborne particulate matter (PM) is a leading cause of mortality and morbidity. However, understanding of the range and mechanisms of effects of PM components is poor. PM generated in underground railways is rich in metals, especially iron. In the ultrafine (UFPM; <0.1 μm diameter) fraction, the combination of small size and metal enrichment poses an unknown health risk. This study aimed to analyse transcriptomic responses to underground UFPM in primary bronchial epithelial cells (PBECs), a key site of PM deposition. The oxidation state of iron in UFPM from an underground station was determined by X-ray absorption near edge structure (XANES) spectroscopy. Antioxidant response was assayed using a reporter cell line transfected with an antioxidant response element (ARE)-luciferase construct. Differentiated PBECs were exposed to UFPM for 6 h or 24 h for RNA-Seq and RT-qPCR analysis. XANES showed predominance of redox-active Fe3O4, with ROS generation confirmed by induction of ARE-luciferase expression. 6 h exposure of PBECs to UFPM identified 52 differentially expressed genes (DEGs), especially associated with epithelial maintenance, whereas 24 h exposure yielded 23 DEGs, particularly involved with redox homeostasis and metal binding. At both timepoints, there was upregulation of members of the metallothionein family, low molecular weight proteins with antioxidant activity whose main function is binding and homeostasis of zinc and copper ions, but not iron ions. This upregulation was partially inhibited by metal chelation or ROS scavenging. These data suggest differential regulation of responses to metal-rich UFPM depending on exposure period, and highlight novel pathways and markers of PM exposure, with the role of metallothioneins warranting further investigation	Apr 2020

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