Full-field strain analysis of bone-biomaterial systems produced by the implantation of osteoregenerative biomaterials in an ovine model

Osteoregenerative biomaterials for the treatment of bone defects are under much development, with the aim of favoring osteointegration up to complete bone regeneration. A detailed investigation of bone–biomaterial integration is vital to understand and predict the ability of such materials to promote bone formation, preventing further bone damage and supporting load-bearing regions. This study aims to characterize the ex vivo micromechanics and microdamage evolution of bone–biomaterial systems at the tissue level, combining high-resolution synchrotron microcomputed tomography, in situ mechanics and digital volume correlation. Results showed that the main microfailure events were localized close to or within the newly formed bone tissue, in proximity to the bone–biomaterial interface. The apparent nominal compressive load applied to the composite structures resulted in a complex loading scenario, mainly due to the higher heterogeneity but also to the different biomaterial degradation mechanisms. The full-field strain distribution allowed characterization of microdamage initiation and progression. The findings reported in this study provide a deeper insight into bone–biomaterial integration and micromechanics in relation to the osteoregeneration achieved in vivo for a variety of biomaterials. This could ultimately be used to improve bone tissue regeneration strategies

Identifying Surrogates for Heart and Ipsilateral Lung Dose to Guide Field Placement and Treatment Modality Selection during Virtual Simulation of Breast Radiotherapy

AIMS: Virtual simulation (VSim) of tangential photon fields is a common method of field localisation for breast radiotherapy. Heart and ipsilateral lung dose is unknown until the dosimetric plan is produced. If heart and ipsilateral lung tolerance doses are exceeded, this can prolong the pre-treatment pathway, particularly if a change of technique is required. The aim of this study was to identify predictive surrogates for heart and ipsilateral lung dose during VSim to aid optimum field placement and treatment modality selection. MATERIALS AND METHODS: Computed tomography data from 50 patients referred for left breast/chest wall radiotherapy were retrospectively analysed (model-building cohort). The prescribed dose was 40.05 Gy in 15 fractions using a tangential photon technique. The heart and ipsilateral lung contours were duplicated, cropped to within the field borders and labelled heart-in-field (HIF) and ipsilateral lung-in-field (ILF). The percentage of HIF (%HIF) and ILF (%ILF) was calculated and correlated with mean heart dose (MHD) and volume of the ipsilateral lung receiving 18 Gy (V18Gy). Linear regression models were calculated. A validation cohort of 10 left- and 10 right-sided cases with an anterior supraclavicular fossa (SCF) field, and 10 left- and 10 right-sided cases including the internal mammary nodes using a wide tangential technique and anterior SCF field, tested the predictive model. Threshold values for %HIF and %ILF were calculated for clinically relevant MHD and ipsilateral lung V18Gy tolerance doses. RESULTS: For the model-building cohort, the median %HIF and MHD were 2.6 (0.4-16.7) and 2.3 (1.2-8) Gy. The median %ILF and ipsilateral lung V18Gy were 12.1 (2.8-33.6) and 12.6 (3.3-35) %. There was a statistically significant strong positive correlation of %HIF with MHD (r2 = 0.97, P < 0.0001) and of %ILF with ipsilateral lung V18Gy (r2 = 0.99, P < 0.0001). For the validation cohort, the median %HIF and MHD were 3.9 (0.6-8) and 2.5 (1.4-4.7) Gy. The median %ILF and ipsilateral lung V18Gy were 20.1 (12.4-32.0) and 20.9 (12.4-34.4) %. The validation cohort confirmed that %HIF and %ILF continue to be predictive surrogates for heart and ipsilateral lung dose during VSim of left- and right-sided cases when including the SCF ± internal mammary nodes with a three-field photon technique. DISCUSSION: The ability to VSim breast radiotherapy (±nodal targets) and accurately predict the heart and ipsilateral lung doses on the dosimetric plan will ensure that tolerance doses are not exceeded, and identify early in the pre-treatment pathway those cases where alternative techniques or modalities should be considered

Quantum interface of an electron and a nuclear ensemble.

Coherent excitation of an ensemble of quantum objects underpins quantum many-body phenomena and offers the opportunity to realize a memory that stores quantum information. Thus far, a deterministic and coherent interface between a spin qubit and such an ensemble has remained elusive. In this study, we first used an electron to cool the mesoscopic nuclear spin ensemble of a semiconductor quantum dot to the nuclear sideband-resolved regime. We then implemented an all-optical approach to access individual quantized electronic-nuclear spin transitions. Lastly, we performed coherent optical rotations of a single collective nuclear spin excitation-a spin wave. These results constitute the building blocks of a dedicated local memory per quantum-dot spin qubit and promise a solid-state platform for quantum-state engineering of isolated many-body systems

Operando and High-throughput multicscale-tomography

We report about multiscale tomography with high throughput at the Diamond beamline I13L. The beamline has the purpose of multi-scale and operando imaging and consists of two independent branchlines operating in real and reciprocal space. The imaging branch -called Diamond-Manchester branchline- hosts micro-tomography, grating interferometry and a full-field microscope. For rapid recording a broad spectrum of the undulator radiation is used either with band-passing the light with a combination of a filter and a deflecting mirror or using a multilayer monochromator. For all the methods similar recording times can be achieved, with typical scanning times of some minutes and covering the resolution range from microns to the 100nm range. Most recently a robot arm has been installed to increase the throughput to 300 samples per day. The system is now implemented for user operation in remote operation mode for the micro-tomography setup and can be expanded to the two other experiments. The instrumental capabilities are applied on various topics such as the study of biodiversity of insects or the structural variations of electrode materials in batteries. Fast recording with dedicated sample environments (not using the sample changing robot) enables operando studies in many areas, the charging/discharging cycles on batteries, the degradation of teeth enamel under various conditions or loading brine sandstone mixtures with CO2, to name some examples. For imaging with highest spatial resolution we managed to improve significantly the recording speed of ptycho-tomography, which is now in the order of hours and will be reduced further. We demonstrated in the past 2-D recording with 10kHz and expand the instrumental capability with specific hardware dependent triggering and scanning schemes. We expand the research program for multi-scale imaging across both branchlines (imaging and coherence branchlines) with first studies such as batteries, brain research, concrete

Preservation of bone tissue integrity with temperature control for in situ SR-MicroCT experiments

© 2018 by the authors. Digital volume correlation (DVC), combined with in situ synchrotron microcomputed tomography (SR-microCT) mechanics, allows for 3D full-field strain measurement in bone at the tissue level. However, long exposures to SR radiation are known to induce bone damage, and reliable experimental protocols able to preserve tissue properties are still lacking. This study aims to propose a proof-of-concept methodology to retain bone tissue integrity, based on residual strain determination using DVC, by decreasing the environmental temperature during in situ SR-microCT testing. Compact and trabecular bone specimens underwent five consecutive full tomographic data collections either at room temperature or 0 °C. Lowering the temperature seemed to reduce microdamage in trabecular bone but had minimal effect on compact bone. A consistent temperature gradient was measured at each exposure period, and its prolonged effect over time may induce localised collagen denaturation and subsequent damage. DVC provided useful information on irradiation-induced microcrack initiation and propagation. Future work is necessary to apply these findings to in situ SR-microCT mechanical tests, and to establish protocols aiming to minimise the SR irradiation-induced damage of bone

Four-dimensional imaging and quantification of viscous flow sintering within a 3D printed bioactive glass scaffold using synchrotron X-ray tomography

Bioglass® was the first material to form a stable chemical bond with human tissue. Since its discovery, a key goal was to produce three-dimensional (3D) porous scaffolds which can host and guide tissue repair, in particular, regeneration of long bone defects resulting from trauma or disease. Producing 3D scaffolds from bioactive glasses is challenging because of crystallization events that occur while the glass particles densify at high temperatures. Bioactive glasses such as the 13–93 composition can be sintered by viscous flow sintering at temperatures above the glass transition onset (T_{g}) and below the crystallization temperature (T_{c}). There is, however, very little literature on viscous flow sintering of bioactive glasses, and none of which focuses on the viscous flow sintering of glass scaffolds in four dimensions (4D) (3D + time). Here, high-resolution synchrotron-sourced X-ray computed tomography (sCT) was used to capture and quantify viscous flow sintering of an additively manufactured bioactive glass scaffold in 4D. In situ sCT allowed the simultaneous quantification of individual particle (local) structural changes and the scaffold's (global) dimensional changes during the sintering cycle. Densification, calculated as change in surface area, occurred in three distinct stages, confirming classical sintering theory. Importantly, our observations show for the first time that the local and global contributions to densification are significantly different at each of these stages: local sintering dominates stages 1 and 2, while global sintering is more prevalent in stage 3. During stage 1, small particles coalesced to larger particles because of their higher driving force for viscous flow at lower temperatures, while large angular particles became less faceted (angular regions had a local small radius of curvature). A transition in the rate of sintering was then observed in which significant viscous flow occurred, resulting in large reduction of surface area, total strut volume, and interparticle porosity because the majority of the printed particles coalesced to become continuous struts (stage 2). Transition from stage 2 to stage 3 was distinctly obvious when interparticle pores became isolated and closed, while the sintering rate significantly reduced. During stage 3, at the local scale, isolated pores either became more spherical or reduced in size and disappeared depending on their initial morphology. During stage 3, sintering of the scaffolds continued at the strut level, with interstrut porosity reducing, while globally the strut diameter increased in size, suggesting overall shrinkage of the scaffold with the flow of material via the strut contacts. This study provides novel insights into viscous flow in a complex non-idealized construct, where, locally, particles are not spherical and are of a range of sizes, leading to a random distribution of interparticle porosity, while globally, predesigned porosity between the struts exists to allow the construct to support tissue growth. This is the first time that the three stages of densification have been captured at the local and global scales simultaneously. The insights provided here should accelerate the development of 3D bioactive glass scaffolds

Structural and functional characterization of Pseudomonas aeruginosa CupB chaperones

Pseudomonas aeruginosa, an important human pathogen, is estimated to be responsible for,10% of nosocomial infections worldwide. The pathogenesis of P. aeruginosa starts from its colonization in the damaged tissue or medical devices (e. g. catheters, prothesis and implanted heart valve etc.) facilitated by several extracellular adhesive factors including fimbrial pili. Several clusters containing fimbrial genes have been previously identified on the P. aeruginosa chromosome and named cup [1]. The assembly of the CupB pili is thought to be coordinated by two chaperones, CupB2 and CupB4. However, due to the lack of structural and biochemical data, their chaperone activities remain speculative. In this study, we report the 2.5 A crystal structure of P. aeruginosa CupB2. Based on the structure, we further tested the binding specificity of CupB2 and CupB4 towards CupB1 (the presumed major pilus subunit) and CupB6 (the putative adhesin) using limited trypsin digestion and strep-tactin pull-down assay. The structural and biochemical data suggest that CupB2 and CupB4 might play different, but not redundant, roles in CupB secretion. CupB2 is likely to be the chaperone of CupB1, and CupB4 could be the chaperone of CupB4:CupB5:CupB6, in which the interaction of CupB4 and CupB6 might be mediated via CupB5

Effect of SR-microCT radiation on the mechanical integrity of trabecular bone using in situ mechanical testing and digital volume correlation

The use of synchrotron radiation micro-computed tomography (SR-microCT) is becoming increasingly popular for studying the relationship between microstructure and bone mechanics subjected to in situ mechanical testing. However, it is well known that the effect of SR X-ray radiation can considerably alter the mechanical properties of bone tissue. Digital volume correlation (DVC) has been extensively used to compute full-field strain distributions in bone specimens subjected to step-wise mechanical loading, but tissue damage from sequential SR-microCT scans has not been previously addressed. Therefore, the aim of this study is to examine the influence of SR irradiation-induced microdamage on the apparent elastic properties of trabecular bone using DVC applied to in situ SR-microCT tomograms obtained with different exposure times. Results showed how DVC was able to identify high local strain levels (> 10,000 µε) corresponding to visible microcracks at high irradiation doses (~ 230 kGy), despite the apparent elastic properties remained unaltered. Microcracks were not detected and bone plasticity was preserved for low irradiation doses (~ 33 kGy), although image quality and consequently, DVC performance were reduced. DVC results suggested some local deterioration of tissue that might have resulted from mechanical strain concentration further enhanced by some level of local irradiation even for low accumulated dose

Preliminary Multiphysics Analyses of HFIR LEU Fuel Conversion using COMSOL

The research documented herein was performed by several individuals across multiple organizations. We have previously acknowledged our funding for the project, but another common thread among the authors of this document, and hence the research performed, is the analysis tool COMSOL. The research has been divided into categories to allow the COMSOL analysis to be performed independently to the extent possible. As will be seen herein, the research has progressed to the point where it is expected that next year (2011) a large fraction of the research will require collaboration of our efforts as we progress almost exclusively into three-dimensional (3D) analysis. To the extent possible, we have tried to segregate the development effort into two-dimensional (2D) analysis in order to arrive at techniques and methodology that can be extended to 3D models in a timely manner. The Research Reactors Division (RRD) of ORNL has contracted with the University of Tennessee, Knoxville (UTK) Mechanical, Aerospace and Biomedical Engineering Department (MABE) to perform a significant fraction of this research. This group has been chosen due to their expertise and long-term commitment in using COMSOL and also because the participating students are able to work onsite on a part-time basis due to the close proximity of UTK with the ORNL campus. The UTK research has been governed by a statement of work (SOW) which clearly defines the specific tasks reported herein on the perspective areas of research. Ph.D. student Isaac T. Bodey has focused on heat transfer, fluid flow, modeling, and meshing issues and has been aided by his major professor Dr. Rao V. Arimilli and is the primary contributor to Section 2 of this report. Ph.D student Franklin G. Curtis has been focusing exclusively on fluid-structure interaction (FSI) due to the mechanical forces acting on the plate caused by the flow and has also been aided by his major professor Dr. Kivanc Ekici and is the primary contributor to Section 4 of this report. The HFIR LEU conversion project has also obtained the services of Dr. Prashant K. Jain of the Reactor & Nuclear Systems Division (RNSD) of ORNL. Prashant has quickly adapted to the COMSOL tools and has been focusing on thermal-structure interaction (TSI) issues and development of alternative 3D model approaches that could yield faster-running solutions. Prashant is the primary contributor to Section 5 of the report. And finally, while incorporating findings from all members of the COMSOL team (i.e., the team) and contributing as the senior COMSOL leader and advocate, Dr. James D. Freels has focused on the 3D model development, cluster deployment, and has contributed primarily to Section 3 and overall integration of this report. The team has migrated to the current release of COMSOL at version 4.1 for all the work described in this report, except where stated otherwise. Just as in the performance of the research, each of the respective sections has been originally authored by the respective authors. Therefore, the reader will observe a contrast in writing style throughout this document