Autologous vs. allogenic mesenchymal progenitor cells for the reconstruction of critical-sized segmental tibial bone defects in aged sheep

Mesenchymal progenitor cells (MPCs) represent an attractive cell population for bone tissue engineering. Their special immunological characteristics suggest that MPCs may be used in an allogenic application. The objective of this study was to compare the regenerative potential of autologous vs. allogenic MPCs in an ovine critical-sized segmental defect model. Ovine MPCs were isolated from bone marrow aspirates, expanded and cultured with osteogenic media for two weeks before implantation. Autologous and allogenic transplantation was performed by using the cell-seeded scaffolds, unloaded scaffolds and the application of autologous bone grafts served as control groups (n=6). Bone healing was assessed twelve weeks after surgery by radiology, micro computed tomography, biomechanical testing and histology. Radiology, biomechanical testing and histology revealed no significant difference in bone formation between the autologous and allogenic group. Both cell groups showed more bone formation than the scaffold alone, whereas the biomechanical data showed no significant differences between the cell-groups and the unloaded scaffolds. The results of the study suggest that scaffold based bone tissue engineering using allogenic cells offers the potential for an off the shelf product. Therefore, the results of this study serve as an important baseline for the translation of the assessed concepts into clinical application.

Dermal fibroblast infiltration of poly(ε-caprolactone) scaffolds fabricated by melt electrospinning in a direct writing mode

Melt electrospinning in a direct writing mode is a recent additive manufacturing approach to fabricate porous scaffolds for tissue engineering applications. In this study, we describe porous and cell-invasive poly (ε-caprolactone) scaffolds fabricated by combining melt electrospinning and a programmable x–y stage. Fibers were 7.5 ± 1.6 µm in diameter and separated by interfiber distances ranging from 8 to 133 µm, with an average of 46 ± 22 µm. Micro-computed tomography revealed that the resulting scaffolds had a highly porous (87%), three-dimensional structure. Due to the high porosity and interconnectivity of the scaffolds, a top-seeding method was adequate to achieve fibroblast penetration, with cells present throughout and underneath the scaffold. This was confirmed histologically, whereby a 3D fibroblast-scaffold construct with full cellular penetration was produced after 14 days in vitro. Immunohistochemistry was used to confirm the presence and even distribution of the key dermal extracellular matrix proteins, collagen type I and fibronectin. These results show that melt electrospinning in a direct writing mode can produce cell invasive scaffolds, using simple top-seeding approaches.

An FE investigation simulating intra-operative corrective forces applied to correct scoliosis deformity

Background: Adolescent idiopathic scoliosis (AIS) is a deformity of the spine, which may 34 require surgical correction by attaching a rod to the patient’s spine using screws 35 implanted in the vertebral bodies. Surgeons achieve an intra-operative reduction in the 36 deformity by applying compressive forces across the intervertebral disc spaces while 37 they secure the rod to the vertebra. We were interested to understand how the 38 deformity correction is influenced by increasing magnitudes of surgical corrective forces 39 and what tissue level stresses are predicted at the vertebral endplates due to the 40 surgical correction. 41 Methods: Patient-specific finite element models of the osseoligamentous spine and 42 ribcage of eight AIS patients who underwent single rod anterior scoliosis surgery were 43 created using pre-operative computed tomography (CT) scans. The surgically altered 44 spine, including titanium rod and vertebral screws, was simulated. The models were 45 analysed using data for intra-operatively measured compressive forces – three load 46 profiles representing the mean and upper and lower standard deviation of this data 47 were analysed. Data for the clinically observed deformity correction (Cobb angle) were 48 compared with the model-predicted correction and the model results investigated to 49 better understand the influence of increased compressive forces on the biomechanics of 50 the instrumented joints. 51 Results: The predicted corrected Cobb angle for seven of the eight FE models were 52 within the 5° clinical Cobb measurement variability for at least one of the force profiles. 53 The largest portion of overall correction was predicted at or near the apical 54 intervertebral disc for all load profiles. Model predictions for four of the eight patients 55 showed endplate-to-endplate contact was occurring on adjacent endplates of one or 56 more intervertebral disc spaces in the instrumented curve following the surgical loading 57 steps. 58 Conclusion: This study demonstrated there is a direct relationship between intra-59 operative joint compressive forces and the degree of deformity correction achieved. The 60 majority of the deformity correction will occur at or in adjacent spinal levels to the apex 61 of the deformity. This study highlighted the importance of the intervertebral disc space 62 anatomy in governing the coronal plane deformity correction and the limit of this 63 correction will be when bone-to-bone contact of the opposing vertebral endplates 64 occurs.

Comparison between analytical and 3D finite element solutions for borehole stresses in anisotropic elastic rock

We present a rigorous validation of the analytical Amadei solution for the stress concentration around an arbitrarily orientated borehole in general anisotropic elastic media. First, we revisit the theoretical framework of the Amadei solution and present analytical insights that show that the solution does indeed contain all special cases of symmetry, contrary to previous understanding, provided that the reduced strain coefficients b11 and b55 are not equal. It is shown from theoretical considerations and published experimental data that the b11 and b55 are not equal for realistic rocks. Second, we develop a 3D finite element elastic model within a hybrid analytical–numerical workflow that circumvents the need to rebuild and remesh the model for every borehole and material orientation. Third, we show that the borehole stresses computed from the numerical model and the analytical solution match almost perfectly for different borehole orientations (vertical, deviated and horizontal) and for several cases involving isotropic, transverse isotropic and orthorhombic symmetries. It is concluded that the analytical Amadei solution is valid with no restriction on the borehole orientation or the symmetry of the elastic anisotropy.

The appearance and effects of metallic implants in CT images

Contemporary 3D radiotherapy treatment planning relies upon the use of 3D electron density maps derived from computed tomography (CT) scans of patient anatomy, to evaluate the effects of that anatomy on radiation dose distributions. Production of these electron density maps requires that the CT numbers (Hounsfield units) that quantify the attenuation of the x-ray beam by the patient’s anatomy must be reliably converted into electron densities, using a stable calibration relationship. This study investigates the fidelity of electron density assignment in the presence of metallic prostheses and implants.

Fixed failure rate ambiguity validation methods for GPS and compass

Ambiguity resolution plays a crucial role in real time kinematic GNSS positioning which gives centimetre precision positioning results if all the ambiguities in each epoch are correctly fixed to integers. However, the incorrectly fixed ambiguities can result in large positioning offset up to several meters without notice. Hence, ambiguity validation is essential to control the ambiguity resolution quality. Currently, the most popular ambiguity validation is ratio test. The criterion of ratio test is often empirically determined. Empirically determined criterion can be dangerous, because a fixed criterion cannot fit all scenarios and does not directly control the ambiguity resolution risk. In practice, depending on the underlying model strength, the ratio test criterion can be too conservative for some model and becomes too risky for others. A more rational test method is to determine the criterion according to the underlying model and user requirement. Miss-detected incorrect integers will lead to a hazardous result, which should be strictly controlled. In ambiguity resolution miss-detected rate is often known as failure rate. In this paper, a fixed failure rate ratio test method is presented and applied in analysis of GPS and Compass positioning scenarios. A fixed failure rate approach is derived from the integer aperture estimation theory, which is theoretically rigorous. The criteria table for ratio test is computed based on extensive data simulations in the approach. The real-time users can determine the ratio test criterion by looking up the criteria table. This method has been applied in medium distance GPS ambiguity resolution but multi-constellation and high dimensional scenarios haven't been discussed so far. In this paper, a general ambiguity validation model is derived based on hypothesis test theory, and fixed failure rate approach is introduced, especially the relationship between ratio test threshold and failure rate is examined. In the last, Factors that influence fixed failure rate approach ratio test threshold is discussed according to extensive data simulation. The result shows that fixed failure rate approach is a more reasonable ambiguity validation method with proper stochastic model.

Establishment and characterisation of an open mini-thoracotomy surgical approach to an ovine thoracic spine fusion model

Background A large animal model is required for assessment of minimally invasive, tissue engineering based approaches to thoracic spine fusion, with relevance to deformity correction surgery for human adolescent idiopathic scoliosis. Here we develop a novel open mini–thoracotomy approach in an ovine model of thoracic interbody fusion which allows assessment of various fusion constructs, with a focus on novel, tissue engineering based interventions. Methods The open mini-thoracotomy surgical approach was developed through a series of mock surgeries, and then applied in a live sheep study. Customized scaffolds were manufactured to conform with intervertebral disc space clearances required of the study. Twelve male Merino sheep aged 4 to 6 years and weighing 35 – 45 kg underwent the abovementioned procedure and were divided into two groups of six sheep at survival timelines of 6 and 12 months. Each sheep underwent a 3-level discectomy (T6/7, T8/9 and T10/11) with randomly allocated implantation of a different graft substitute at each of the three levels; (i) polycaprolactone (PCL) based scaffold plus 0.54μg rhBMP-2, (ii) PCL-based scaffold alone or (iii) autograft. The sheep were closely monitored post- operatively for signs of pain (i.e. gait abnormalities/ teeth gnawing/ social isolation). Fusion assessments were conducted post-sacrifice using Computed Tomography and hard-tissue histology. All scientific work was undertaken in accordance with the study protocol has been approved by the Institute's committee on animal research. Results. All twelve sheep were successfully operated on and reached the allotted survival timelines, thereby demonstrating the feasibility of the surgical procedure and post-operative care. There were no significant complications and during the post-operative period the animals did not exhibit marked signs of distress according to the described assessment criteria. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL-based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by histological evaluation of the respective groups. Conclusion. This novel open mini-thoracotomy surgical approach to the ovine thoracic spine represents a safe surgical method which can reproducibly form the platform for research into various spine tissue engineered constructs (TEC) and their fusion promoting properties.

Biological performance of a polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

Introduction. We develop a sheep thoracic spine interbody fusion model to study the suitability of polycaprolactone-based scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within the thoracic spine. The surgical approach is a mini- open thoracotomy with relevance to minimally invasive deformity correction surgery for adolescent idiopathic scoliosis. To date there are no studies examining the use of this biodegradable implant in combination with biologics in a sheep thoracic spine model. Methods. In the present study, six sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone based scaffold plus 0.54µg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion was assessed at six months post-surgery. Results. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL- based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by histological evaluations of the respective groups. Biomechanical testing revealed significantly higher stiffness for the rhBMP-2 plus PCL- based scaffold group in all loading directions in comparison to the other two groups. Conclusions. The results of this study demonstrate that rhBMP-2 plus PCL-based scaffold is a viable bone graft substitute, providing an optimal environment for thoracic interbody spinal fusion in a large animal model.

Inter-vertebral rotational deformity after endoscopic anterior scoliosis correction may contribute to rib hump recurrence after two years

Introduction. Endoscopic anterior scoliosis correction has been employed recently as a less invasive and level-sparing approach compared with open surgical techniques. We have previously demonstrated that during the two-year post-operative period, there was a mean loss of rib hump correction by 1.4 degrees. The purpose of this study was to determine whether intra- or inter-vertebral rotational deformity during the post-operative period could account for the loss of rib hump correction. Materials and Methods. Ten consecutive patients diagnosed with adolescent idiopathic scoliosis were treated with an endoscopic anterior scoliosis correction. Low-dose computed tomography scans of the instrumented segment were obtained post-operatively at 6 and 24 months following institutional ethical approval and patient consent. Three-dimensional multi-planar reconstruction software (Osirix Imaging Software, Pixmeo, Switzerland) was used to create axial slices of each vertebral level, corrected in both coronal and sagittal planes. Vertebral rotation was measured using Ho’s method for every available superior and inferior endplate at 6 and 24 months. Positive changes in rotation indicate a reduction and improvement in vertebral rotation. Intra-observer variability analysis was performed on a subgroup of images. Results. Mean change in rotation for vertebral endplates between 6 and 24 months post-operatively was -0.26˚ (range -3.5 to 4.9˚) within the fused segment and +1.26˚ (range -7.2 to 15.1˚) for the un-instrumented vertebrae above and below the fusion. Mean change in clinically measured rib hump for the 10 patients was -1.6˚ (range -3 to 0˚). The small change in rotation within the fused segment accounts for only 16.5% of the change in rib hump measured clinically whereas the change in rotation between the un-instrumented vertebrae above and below the construct accounts for 78.8%. There was no clear association between rib hump recurrence and intra- or inter-vertebral rotation in individual patients. Intra-rater variability was ± 3˚. Conclusions. Intra- and inter-vertebral rotation continues post-operatively both within the instrumented and un-instrumented segments of the immature spine. Rotation between the un-instrumented vertebrae above and below the fusion was +1.26˚, suggesting that the un-instrumented vertebrae improved and de-rotated slightly after surgery. This may play a role in rib hump recurrence, however this remains clinically insignificant.

Achieving high reliability for ambiguity resolutions with multiple GNSS constellations

Global Navigation Satellite Systems (GNSS)-based observation systems can provide high precision positioning and navigation solutions in real time, in the order of subcentimetre if we make use of carrier phase measurements in the differential mode and deal with all the bias and noise terms well. However, these carrier phase measurements are ambiguous due to unknown, integer numbers of cycles. One key challenge in the differential carrier phase mode is to fix the integer ambiguities correctly. On the other hand, in the safety of life or liability-critical applications, such as for vehicle safety positioning and aviation, not only is high accuracy required, but also the reliability requirement is important. This PhD research studies to achieve high reliability for ambiguity resolution (AR) in a multi-GNSS environment. GNSS ambiguity estimation and validation problems are the focus of the research effort. Particularly, we study the case of multiple constellations that include initial to full operations of foreseeable Galileo, GLONASS and Compass and QZSS navigation systems from next few years to the end of the decade. Since real observation data is only available from GPS and GLONASS systems, the simulation method named Virtual Galileo Constellation (VGC) is applied to generate observational data from another constellation in the data analysis. In addition, both full ambiguity resolution (FAR) and partial ambiguity resolution (PAR) algorithms are used in processing single and dual constellation data. Firstly, a brief overview of related work on AR methods and reliability theory is given. Next, a modified inverse integer Cholesky decorrelation method and its performance on AR are presented. Subsequently, a new measure of decorrelation performance called orthogonality defect is introduced and compared with other measures. Furthermore, a new AR scheme considering the ambiguity validation requirement in the control of the search space size is proposed to improve the search efficiency. With respect to the reliability of AR, we also discuss the computation of the ambiguity success rate (ASR) and confirm that the success rate computed with the integer bootstrapping method is quite a sharp approximation to the actual integer least-squares (ILS) method success rate. The advantages of multi-GNSS constellations are examined in terms of the PAR technique involving the predefined ASR. Finally, a novel satellite selection algorithm for reliable ambiguity resolution called SARA is developed. In summary, the study demonstrats that when the ASR is close to one, the reliability of AR can be guaranteed and the ambiguity validation is effective. The work then focuses on new strategies to improve the ASR, including a partial ambiguity resolution procedure with a predefined success rate and a novel satellite selection strategy with a high success rate. The proposed strategies bring significant benefits of multi-GNSS signals to real-time high precision and high reliability positioning services.

Online calibration of stereo rigs for long-term autonomy

Stereo-based visual odometry algorithms are heavily dependent on an accurate calibration of the rigidly fixed stereo pair. Even small shifts in the rigid transform between the cameras can impact on feature matching and 3D scene triangulation, adversely affecting pose estimates and applications dependent on long-term autonomy. In many field-based scenarios where vibration, knocks and pressure change affect a robotic vehicle, maintaining an accurate stereo calibration cannot be guaranteed over long periods. This paper presents a novel method of recalibrating overlapping stereo camera rigs from online visual data while simultaneously providing an up-to-date and up-to-scale pose estimate. The proposed technique implements a novel form of partitioned bundle adjustment that explicitly includes the homogeneous transform between a stereo camera pair to generate an optimal calibration. Pose estimates are computed in parallel to the calibration, providing online recalibration which seamlessly integrates into a stereo visual odometry framework. We present results demonstrating accurate performance of the algorithm on both simulated scenarios and real data gathered from a wide-baseline stereo pair on a ground vehicle traversing urban roads.

Quantitative evaluation of polymer gel dosimeters by broadband ultrasound attenuation

Ultrasound has been examined previously as an alternative readout method for irradiated polymer gel dosimeters, with authors reporting varying dose response to ultrasound transmission measurements. In this current work we extend previous work to measure the broadband ultrasound attenuation (BUA) response of irradiated PAGAT gel dosimeters, using a novel ultrasound computed tomography system.

A density functional theory study on CO2 capture and activation by graphene-like boron nitride with boron vacancy

First principle calculations for a hexagonal (graphene-like) boron nitride (g-BN) monolayer sheet in the presence of a boron-atom vacancy show promising properties for capture and activation of carbon dioxide. CO2 is found to decompose to produce an oxygen molecule via an intermediate chemisorption state on the defect g-BN sheet. The three stationary states and two transition states in the reaction pathway are confirmed by minimum energy pathway search and frequency analysis. The values computed for the two energy barriers involved in this catalytic reaction after enthalpy correction indicate that the catalytic reaction should proceed readily at room temperature.

First-principle studies of the formation and diffusion of hydrogen vacancies in magnesium hydride

Ab initio density functional theory (DFT) calculations are performed to study the formation and diffusion of hydrogen vacancies on MgH2(110) surface and in bulk. We find that the formation energies for a single H-vacancy increase slightly from the surface to deep layers. The energies for creating adjacent surface divancacies at two inplane sites and at an inplane and a bridge site are even smaller than that for the formation of a single H-vacancy, a fact that is attributed to the strong vacancy−vacancy interactions. The diffusion of an H-vacancy from an in-plane site to a bridge site on the surface has the smallest activation barrier calculated at 0.15 eV and should be fast at room temperature. The activation barriers computed for H-vacancy diffusion from the surface into sublayers are all less than 0.70 eV, which is much smaller than the activation energy for desorption of hydrogen on the MgH2(110) surface (1.78−2.80 eV/H2). This suggests that surface desorption is more likely than vacancy diffusion to be rate determining, such that finding effective catalyst on the MgH2 surface to facilitate desorption will be very important for improving overall dehydrogenation performance.

Addition of diazomethane to armchair single-walled carbon nanotubes and their reaction sequences : A computational study

The sidewall additions of diazomethane to (n, n), n = 3–10 armchair single-walled carbon nanotubes (SWCNTs) on two different orientations of C–C bonds have been studied using the ONIOM(B3LYP/6-31G(d):PM3) approach. The binding energies of SWCNTs complexes with CH2N2, CH2 and their transition-state structures were computed at the B3LYP/6-31G(d) level. The effects of diameters of armchair SWCNTs on their binding energies were studied. Relative reactivities of all the SWCNTs and their complexes based on their frontier orbital energies gaps are reported.