Reference number : GC-2017-Q1-02915, amendment number : , agreement type : G, recipient legal name : Addison, Owen (University of Alberta), recipient country : CA, recipient province : nan, recipient city : Alberta, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : Metallic biomaterials are used as part of routine healthcare to replace or repair lost or damaged tissues but the currently used materials are frequently associated with adverse biological responses. These events are linked to either infection or to biological responses to implant derivatives (metal surfaces, particles, ions, and metal modified bio-molecules) or a combination. A key deficiency is our understanding of the physico-chemical environment which develops around the failing implant. Whilst there are numerous industrial and academic led programs aiming to develop new alloys and surfaces we still have an inadequate understanding of the form implant metal derivatives are found in tissues and with which cells and biological pathways they interact. 
 
We take the approach that to really understand how to develop the next generation of metallic biomaterials we must be able to understand how they behave, not just after 1, 2 or 3 years, but after several decades. To achieve this, our previous work has highlighted a number of areas where technological developments falling within the NSERC remit will be required. Over the course of this discovery grant we aim to: 
 
Firstly, develop novel correlative synchrotron radiation-X-Ray fluorescence (SR-XRF)/ X-ray absorption spectroscopic (XAS) imaging protocols. 2D SR-XRF measurements on tissues and on cell populations are well established but data is infrequently correlated with the underlying tissue composition. Analysis is complicated by sample distortion and is most complicated where heterogeneous elemental distributions exist (such as peri-implant tissues). Taking advantage of the fact that L-III energy edges of Lanthanides lie close to the k-edge excitation energies of common biomedical alloy elements (Co, Cr, &amp; Ti) we aim to develop techniques using a single imaging modality and secondary (lanthanide) metal-conjugated antibodies to discriminate the underlying cellular composition, whilst at the same time allowing understanding of the location and speciation of elements of interest. 
 
Secondly, develop methods to allow more biologically informed implant materials and device development. We will develop methods based on our pilot data to simulate corrosion behavior and implant derivative release that is more representative of long-term device performance. Working with external established collaborative partners who are developing novel alloys including Ti-based bulk metallic glasses (see-CCV H2020-MSCA-IF-GLASSIX) we will simulate biocorrosion and mechanically assisted corrosion behavior (of promising compositions) prior to biological compatibility testing using a panel of established assays. These &lsquo;conventional&rsquo; biological assays will be complemented by SR-XAS measurements to validate exposures and monitor subsequent cellular mediated modifications to the speciation of the implant derived products., program purpose french : Metallic biomaterials are used as part of routine healthcare to replace or repair lost or damaged tissues but the currently used materials are frequently associated with adverse biological responses. These events are linked to either infection or to biological responses to implant derivatives (metal surfaces, particles, ions, and metal modified bio-molecules) or a combination. A key deficiency is our understanding of the physico-chemical environment which develops around the failing implant. Whilst there are numerous industrial and academic led programs aiming to develop new alloys and surfaces we still have an inadequate understanding of the form implant metal derivatives are found in tissues and with which cells and biological pathways they interact. 
 
We take the approach that to really understand how to develop the next generation of metallic biomaterials we must be able to understand how they behave, not just after 1, 2 or 3 years, but after several decades. To achieve this, our previous work has highlighted a number of areas where technological developments falling within the NSERC remit will be required. Over the course of this discovery grant we aim to: 
 
Firstly, develop novel correlative synchrotron radiation-X-Ray fluorescence (SR-XRF)/ X-ray absorption spectroscopic (XAS) imaging protocols. 2D SR-XRF measurements on tissues and on cell populations are well established but data is infrequently correlated with the underlying tissue composition. Analysis is complicated by sample distortion and is most complicated where heterogeneous elemental distributions exist (such as peri-implant tissues). Taking advantage of the fact that L-III energy edges of Lanthanides lie close to the k-edge excitation energies of common biomedical alloy elements (Co, Cr, &amp; Ti) we aim to develop techniques using a single imaging modality and secondary (lanthanide) metal-conjugated antibodies to discriminate the underlying cellular composition, whilst at the same time allowing understanding of the location and speciation of elements of interest. 
 
Secondly, develop methods to allow more biologically informed implant materials and device development. We will develop methods based on our pilot data to simulate corrosion behavior and implant derivative release that is more representative of long-term device performance. Working with external established collaborative partners who are developing novel alloys including Ti-based bulk metallic glasses (see-CCV H2020-MSCA-IF-GLASSIX) we will simulate biocorrosion and mechanically assisted corrosion behavior (of promising compositions) prior to biological compatibility testing using a panel of established assays. These &lsquo;conventional&rsquo; biological assays will be complemented by SR-XAS measurements to validate exposures and monitor subsequent cellular mediated modifications to the speciation of the implant derived products., agreement title english : Advancing biophysical measurements to provide a better understanding of peri-implant inflammation and to inform materials development., agreement title french : Advancing biophysical measurements to provide a better understanding of peri-implant inflammation and to inform materials development., agreement number : RGPIN, agreement value : 120000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada