38 results found
Kazezian Z, Yu X, Ramette M, et al., 2020, Development of a blast injury model for investigating conditions associated with traumatic amputations, ORS 2021 Annual Meeting
Campos-Pires R, Yonis A, Pau A, et al., 2019, Delayed xenon treatment prevents injury development following blast-neurotrauma in vitro, 37th Annual National Neurotrauma Symposium, Publisher: Mary Ann Liebert, Pages: A40-A41, ISSN: 0897-7151
Campos Pires R, Yonis A, Macdonald W, et al., 2018, A novel In vitro model of blast traumatic brain injury, Jove-Journal of Visualized Experiments, Vol: 142, ISSN: 1940-087X
Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the detonation of explosive devices, however, the mechanisms that underlie the brain damage resulting from blast overpressure exposure are not entirely understood and are believed to be unique to this type of brain injury. Preclinical models are crucial tools that contribute to better understand blast-induced brain injury. A novel in vitro blast TBI model was developed using an open-ended shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform. C57BL/6N mouse organotypic hippocampal slice cultures were exposed to single shock waves and the development of injury was characterized up to 72 h using propidium iodide, a well-established fluorescent marker of cell damage that only penetrates cells with compromised cellular membranes. Propidium iodide fluorescence was significantly higher in the slices exposed to a blast wave when compared with sham slices throughout the duration of the protocol. The brain tissue injury is very reproducible and proportional to the peak overpressure of the shock wave applied.
Campos-Pires R, Yonis A, Pau A, et al., 2018, Xenon is neuroprotective against blast traumatic brain injury in vitro, Anaesthetic Research Society Meeting, Publisher: Elsevier, Pages: e23-e23, ISSN: 1471-6771
Lamb LE, Siggins MK, Scudamore C, et al., 2018, Impact of contusion injury on intramuscular emm1 group A-Streptococcus infection and Lymphatic spread, Virulence, Vol: 9, Pages: 1074-1084, ISSN: 2150-5594
Invasive group A Streptococcus (iGAS) is frequently associated with emm1 isolates, with an attendant mortality of around 20%. Cases occasionally arise in previously healthy individuals with a history of upper respiratory tract infection, soft tissue contusion, and no obvious portal of entry. Using a new murine model of contusion, we determined the impact of contusion on iGAS bacterial burden and phenotype. Calibrated mild blunt contusion did not provide a focus for initiation or seeding of GAS that was detectable following systemic GAS bacteremia, but instead enhanced GAS migration to the local draining lymph node following GAS inoculation at the same time and site of contusion. Increased migration to lymph node was associated with emergence of mucoid bacteria, although was not specific to mucoid bacteria. In one study, mucoid colonies demonstrated a significant increase in capsular hyaluronan that was not linked to a covRS or rocA mutation, but to a deletion in the promoter of the capsule synthesis locus, hasABC, resulting in a strain with increased fitness for lymph node migration. In summary, in the mild contusion model used, we could not detect seeding of muscle by GAS. Contusion promoted bacterial transit to the local lymph node. The consequences of contusion-associated bacterial lymphatic migration may vary depending on the pathogen and virulence traits selected.
Campos Pires R, Koziakova M, Yonis A, et al., 2018, Xenon protects against blast-induced traumatic brain injury in an in vitro model, Journal of Neurotrauma, Vol: 35, Pages: 1037-1044, ISSN: 0897-7151
The aim of this study was to evaluate the neuroprotective efficacy of the inert gas xenon as a treatment for patients with blast-induced traumatic brain injury in an in vitro laboratory model. We developed a novel blast traumatic brain injury model using C57BL/6N mouse organotypic hippocampal brain-slice cultures exposed to a single shockwave, with the resulting injury quantified using propidium iodide fluorescence. A shock tube blast generator was used to simulate open field explosive blast shockwaves, modeled by the Friedlander waveform. Exposure to blast shockwave resulted in significant (p < 0.01) injury that increased with peak-overpressure and impulse of the shockwave, and which exhibited a secondary injury development up to 72 h after trauma. Blast-induced propidium iodide fluorescence overlapped with cleaved caspase-3 immunofluorescence, indicating that shock-wave–induced cell death involves apoptosis. Xenon (50% atm) applied 1 h after blast exposure reduced injury 24 h (p < 0.01), 48 h (p < 0.05), and 72 h (p < 0.001) later, compared with untreated control injury. Xenon-treated injured slices were not significantly different from uninjured sham slices at 24 h and 72 h. We demonstrate for the first time that xenon treatment after blast traumatic brain injury reduces initial injury and prevents subsequent injury development in vitro. Our findings support the idea that xenon may be a potential first-line treatment for those with blast-induced traumatic brain injury.
Britzman D, Igah I, Eftaxiopoulou T, et al., 2018, Tibial osteotomy as a mechanical model of primary osteoarthritis in rats, Scientific Reports, Vol: 8, ISSN: 2045-2322
This study has presented the ﬁrst purely biomechanical surgical model of osteoarthritis (OA) in rats, which could be more representative of the human primary disease than intra-articular techniques published previously. A surgical tibial osteotomy (TO) was used to induce degenerative cartilage changes in the medial knee of Sprague-Dawley rats. The presence of osteoarthritic changes in the medial knee compartment of the operated animals was evaluated histologically and through analysis of serum carboxy-terminal telepeptides of type II collagen (CTX-II). In-vivo biomechanical analyses were carried out using a musculoskeletal model of the rat hindlimb to evaluate the loading conditions in the knee pre and post-surgically. Qualitative and quantitative medial cartilage degeneration consistent with OA was found in the knees of the operated animals alongside elevated CTX-II levels and increased tibial compressive loading. The potential avoidance of joint inﬂammation post-surgically, the maintenance of internal joint biomechanics and the ability to quantify the alterations in joint loading should make this model of OA a better candidate for modeling primary forms of the disease in humans.
Barnett-Vanes A, Sharrock A, Eftaxiopoulou T, et al., 2016, CD43Lo classical monocytes participate in the cellular immune response to isolated primary blast lung injury, Journal of Trauma and Acute Care Surgery, Vol: 81, Pages: 500-511, ISSN: 2163-0763
BACKGROUND: Understanding of the cellular immune response to primary blast lung injury (PBLI) is limited, with only the neutrophil response well documented. Moreover, its impact on the immune response in distal organs remains poorly understood. In this study, a rodent model of isolated primary blast injury was used to investigate the acute cellular immune response to isolated PBLI in the circulation and lung; including the monocyte response, and investigate distal sub-acute immune effects in the spleen and liver 6hr after injury. METHODS: Rats were subjected to a shock wave (~135kPa overpressure, 2ms duration) inducing PBLI or sham procedure. Rat physiology was monitored and at 1, 3 and 6 hr thereafter blood, lung, and Broncho-alveolar lavage fluid (BALF) were collected and analysed by flow cytometry (FCM), ELISA and Histology. In addition, at 6hr spleen and liver were collected and analysed by FCM. RESULTS: Lung histology confirmed pulmonary barotrauma and inflammation. This was associated with rises in CXCL-1, IL-6, TNF-α and albumin protein in the BALF. Significant acute increases in blood and lung neutrophils and CD43Lo/His48Hi (classical) monocytes/macrophages were detected. No significant changes were seen in blood or lung 'non-classical' monocyte, NK, B or T Cells. In the BALF, significant increases were seen in neutrophils, CD43Lo monocyte-macrophages and MCP-1. Significant increases in CD43Lo and Hi monocyte-macrophages were detected in the spleen at 6hr. CONCLUSIONS: This study reveals a robust and selective response of CD43Lo/His48Hi (classical) monocytes - in addition to neutrophils - in blood and lung tissue following PBLI. An increase in monocyte-macrophages was also observed in the spleen at 6hr. This profile of immune cells in the blood and BALF could present a new research tool for translational studies seeking to monitor, assess or attenuate the immune response in blast injured patients. EVIDENCE: Experimental laboratory study.WC- 300.
Eftaxiopoulou T, Barnett-Vanes A, Arora H, et al., 2016, Prolonged but not short duration blast waves elicit acute inflammation in a rodent model of primary blast limb trauma, Injury, Vol: 47, Pages: 625-632, ISSN: 0020-1383
BackgroundBlast injuries from conventional and improvised explosive devices account for 75% of injuries from current conflicts; of these over 70% involve the limbs. Variable duration and magnitude of blast wave loading occurs in real-life explosions and is hypothesised to cause different injuries. While a number of in-vivo models report the inflammatory response to blast injuries, the extent of this response has not been investigated with respect to the duration of the primary blast wave. The relevance is that explosions in open air are of short duration compared to those in confined spaces. MethodsHind limbs of adult Sprauge-Dawley rats were subjected to focal isolated primary blast waves of varying overpressure (1.8-3.65kPa) and duration (3.0-11.5ms), utilising a shock tube and purpose built experimental rig. Rats were monitored during and after blast. At 6 and 24hrs after exposure blood, lungs, liver and muscle tissue were collected and prepared for histology and flow cytometry.ResultsAt 6hrs increases in circulating neutrophils and CD43Lo/His48Hi monocytes were observed in rats subjected to longer duration blast waves. This was accompanied by increases in circulating pro-inflammatory chemo/cytokines KC and IL-6. No changes were observed with shorter duration blast waves irrespective of overpressure. In all cases, no histological damage was observed in muscle, lung or liver. By 24hrs post-blast all inflammatory parameters had normalised. ConclusionsWe report the development of a rodent model of primary blast limb trauma that is the first to highlight an important role played by blast wave duration and magnitude in initiating acute inflammatory response following limb injury in the absence of limb fracture or penetrating trauma. The combined biological and mechanical method developed can be used to further understand the complex effects of blast waves in a range of different tissues and organs in-vivo.
Lamb L, MacDonald W, Scudamore C, et al., 2015, THE EFFECT OF TRAUMA ON INVASIVE GROUP A STREPTOCOCCAL (IGAS) DISEASE, JOURNAL OF INFECTION, Vol: 71, Pages: 686-686, ISSN: 0163-4453
Eftaxiopoulou T, Macdonald W, Britzman D, et al., 2014, Gait compensations in rats after a temporary nerve palsy quantified using temporo-spatial and kinematic parameters, JOURNAL OF NEUROSCIENCE METHODS, Vol: 232, Pages: 16-23, ISSN: 0165-0270
Macdonald W, Shefelbine SR, 2013, Characterising neovascularisation in fracture healing with laser Doppler and micro-CT scanning., Medical & Biological Engineering & Computing., Vol: 51, Pages: 1157-1165
Nguyen TT, Wilgeroth J, Macdonald W, et al., 2013, Methods of Controlled Shock Wave Generation in A Shock Tube for Biological Applications, Bulletin of the American Physical Society, Vol: 58
The shock tube is a versatile yet simple equipment used in a wide range of scientific research. The diaphragm breakage process, manipulated by different operation methods, is closely linked to the shock wave generated. Experiments were performed on a compressed air-driven shock tube with mylar and aluminium diaphragms of various thicknesses to characterise the output. The evolution of the pressure generated was measured and the diaphragm rupture investigated. Single-diaphragm and double-diaphragm configurations were employed, as were open or closed tube configurations. The arrangement was designed to enable high-speed photography and pressure measurements. Overall, results are highly reproducible, and show that the double-diaphragm system enables a more controllable diaphragm burst pressure. The diaphragm burst pressure was linearly related to its thickness within the range studied. The observed relationship between the diaphragm burst pressure and the generated shock pressure presents a noticeable difference compared to the theoretical ideal gas description. Furthermore, the duration of the primary shock decreased with the volume of the high-pressure charging gas. Computational modelling of the diaphragm breakage process was carried out using the ANSYS software package.
Albrektsson T, Carlsson L, Jacobsson M, et al., 2007, Femur Fixture and set of Femur Fixtures, 7156879
Carlsson LV, Albrektsson BE, Albrektsson BG, et al., 2006, Stepwise introduction of a bone-conserving osseointegrated hip arthroplasty using RSA and a randomized study: I. Preliminary investigations--52 patients followed for 3 years, Acta Orthop, Vol: 77, Pages: 549-558
BACKGROUND: We developed a total hip system using osseointegration guidelines, a metaphyseal-loading proximal femoral replacement in the retained neck and a dual-geometry titanium shell in the acetabulum. PATIENTS AND METHODS: A randomized controlled clinical trial was undertaken in 52 patients (53 hips), using the cemented Spectron stem and cementless Harris-Galante II cup as control implants (24 patients in experimental group, 29 control patients). Clinical measures of Harris Hip Score (HHS), pain score and radiostereometric analysis (RSA) at regular intervals for up to three years were used to monitor progress. RESULTS: No statistically significant differences were found in HHS and pain score; the stability of the cementless experimental implant was also comparable to that of the cemented controls by RSA. 3 revisions were required for migration in the experimental group and 1 was required for component dislocation in the control group. INTERPRETATION: Our findings indicate the practicality of osseointegration of titanium implants, but suggest that current performance is inadequate for clinical introduction. However, the stable fixation achieved in the retained neck in the majority of patients is indicative of osseointegration. This finding will encourage technical and design improvements for enhancement of clinical osseointegration and should also encourage further study. Periprosthetic osteolysis might be avoided by the establishment and maintenance of direct implant-bone connection: "osseointegration".
Carlsson LV, Albrektsson T, Albrektsson BE, et al., 2006, Stepwise introduction of a bone-conserving osseointegrated hip arthroplasty using RSA and a randomized study: II. Clinical proof of concept--40 patients followed for 2 years, Acta Orthop, Vol: 77, Pages: 559-566
BACKGROUND: We have developed a bone-conserving commercially pure titanium hip replacement system using osseointegration principles: a metaphyseal loading proximal femoral component affixing into the retained neck and metaphysis only, leaving the femoral canal untouched. The acetabular cup closely fits a dual-geometry cavity, avoiding stress protection at the dome. PATIENTS AND METHODS: After extensive laboratory and clinical pilot trial investigations, the surface-engineered implants were submitted to a prospective randomized controlled clinical trial involving 40 patients (40 hips), in which they were compared to the cemented Spectron femoral component and cementless Trilogy cup as control implant. The following clinical measures were used to monitor progress at regular intervals for the first 2 postoperative years: radiostereometric analysis (RSA), Harris Hip Score, pain score, WOMAC, and SF-36. RESULTS: After 2 years of follow-up, no statistically significant differences were seen between the groups concerning rotation or translation along the cardinal axes. The patients receiving the Gothenburg osseointegrated titanium (GOT) system had significantly higher Harris Hip Score at 6 months, suggesting more rapid recovery. WOMAC, SF-36 and pain analysis were similar for the first 2 postoperative years. INTERPRETATION: Our RSA data suggest that osseointegration was achieved for all patients receiving the GOT hip system. This bone-conserving prosthesis may provide a good alternative, especially for young and active patients.
Macdonald W, 2005, Fracture Healing
Albrektsson T, Carlsson L, Jacobsson M, et al., 2004, Implant, 6824568
Macdonald W, Campbell P, Fisher J, et al., 2004, Variation in surface texture measurements, J Biomed Mater Res B Appl Biomater, Vol: 70, Pages: 262-269
Surface texture influences cellular response to implants, implant wear, and fixation, yet measurement and reporting of surface texture can be confusing and ambiguous. Seven specimens of widely different surface textures were submitted to three internationally renowned laboratories for surface texture characterization. The specimens were from dental implants, orthopedic implants, and femoral heads. Areas to be measured were clearly marked; simplified instructions were supplied but specific measurement parameters were not requested. Techniques used included contact profilometry, two- and three-dimensional laser profilometry, and atomic force microscopy. Four to thirteen parameters were reported, 2D or 3D, including R(a) or S(a); only three were common to all centers. The results varied by as much as +/-300-1000%, depending on technique and surface type. Some surfaces were not measurable by some techniques. One dental implant surface was reported with R(a) of 0.17, 0.85, 1.9, and 4.4 microm. The CoCr femoral head ranged from an R(a) of 0.011 to 0.10 microm; the zirconia head from 0.006 to 0.05 microm. Similar variability was reported for the other parameters. Useful surface texture characterization requires reporting of all measurement parameters. Comparisons between studies may be compromised if differences in technique are not considered.
Macdonald W, Styf J, Carlsson LV, et al., 2004, Improved tibial cutting accuracy in knee arthroplasty, Med Eng Phys, Vol: 26, Pages: 807-812
Initial stability and development of long-term fixation for cementless tibial components at the knee both depend on the accuracy of fit between implanted components and prepared bone surfaces. Tibial surfaces prepared for total knee replacement with conventional saw-blades and guides were shown by Toksvig-Larsen to vary by over 2 mm, from a flat surface at the point of maximum variation, and all points varied with a standard deviation of up to 0.4 mm. Surface cutting errors are caused by flexion of the saw-blade and blade angulation from the ideal alignment, due to poor guidance or control by the saw-block or guide. Most conventional knee instrumentation relies on flat surface or slotted cutting blocks, constraining the moving saw-blade against one or two guide surfaces. Improved cutting action was achieved by constraining the saw from the pivot point of the blade, and controlling motion of this constraint with parallel action slides. Using this saw-guide and an improved saw-blade, tibial cuts were made in mock arthroplasty procedures on twenty four cadaveric tibiae in mortuo. Analysis of Variance and Tukey's HSD test showed that the improved saw technique yielded significantly better flatness (p < 0.03) and greatly improved roughness (p < 0.0005).
Macdonald W, Carlsson LV, Gathercole N, et al., 2003, Fatigue testing of a proximal femoral hip component, Proc Inst Mech Eng [H], Vol: 217, Pages: 137-145, ISSN: 0954-4119
The Gothenburg Osseointegrated Titanium (GOT) implant is a novel total hip replacement including a metaphyseal loading proximal femoral component fixed in the retained femoral neck. Endurance testing was performed under conditions analogous to ISO 7206-4: 1989. The cement-free implant is not fixed distally within the intramedullary canal, so distal embedding (as specified in the standard) would have been unrealistic. Instead glass-fibre-reinforced epoxy (GFRE) bushings were used to model reduced bone support mid-length at the medial cortex and distally at the lateral cortex. Such support simulated proximal bone loss, realistically reproducing the effect of osteolysis or fixation failure. Under such conditions the component survived unbroken for 10 million cycles at 3.0 kN peak load.
Macdonald W, Carlsson LV, Jacobsson CM, et al., 2003, A proximal femoral implant preserves physiological bone deformation: a biomechanical investigation in cadaveric bones, Proc Inst Mech Eng [H], Vol: 217, Pages: 41-48
The aim of this study was to compare the perturbances in bone deformation patterns of the proximal femur due to a conventional cemented femoral stem and a novel uncemented implant designed on the principles of osseointegration. Five matched pairs of fresh frozen human femora were mechanically tested. Bone deformation patterns, measured with a video digitizing system under 1.5 kN joint force, showed that the cemented Spectron femoral implant caused significant alterations to the proximal femoral deformation pattern, whereas the Gothenburg osseointegrated titanium femoral implant did not significantly alter the bone behaviour (p < 0.05). Vertical micromotions measured under 1 kN after 1000 cycles were within the threshold of movement tolerable for bone ingrowth (21 microm for the Gothenburg system and 26 microm for the cemented implant).
Macdonald W, Aspenberg A, Jacobsson CM, et al., 2003, A novel liner locking mechanism enhances retention stability, Med Eng Phys, Vol: 25, Pages: 747-754, ISSN: 1350-4533
Acetabular liner retention of a novel design of liner locking was evaluated in static and cyclic endurance modes. The locking mechanism combines geometric form and accurate machining to give high conformity to the acetabular shell and minimise relative motion against the metal shell, minimising debris generation and escape or ingress. Using amended test liners with integral coupling, mean static pullout strength was determined to be 399+/-53 N and lever-out strength 28.03+/-2.8 N m. Cyclic loading of 5 N m for up to 10 million cycles caused no significant reduction in strength, no detectable fretting wear, and the sealing mechanism prevented particle access between the cup interior and the "effective joint space". The stability measured ensures secure and reliable in vivo retention of the liner, comparable with extant component designs using other liner locking mechanisms.
Albrektsson T, Jacobsson M, Wennberg S, et al., 2002, Femoral Fixture for a Hip Joint Prosthesis
Albrektsson T, Carlsson L, Jacobsson M, et al., 2001, Femur Fixture and set of femur fixtures
Albrektsson T, Carlsson L, Jacobsson M, et al., 2001, Implant
Macdonald W, Aspenberg A, Jacobsson CM, et al., 2000, Friction in orthopaedic zirconia taper assemblies, Proc Inst Mech Eng [H], Vol: 214, Pages: 685-692, ISSN: 0954-4119
The torque resistance of zirconia ceramic heads/titanium taper trunnion junctions was tested in accordance with ISO 7206-9:1994(E); using twelve modified heads of 32 mm diameter under representative physiological conditions. Test parameters studied included assembly force, vertical load during test (test load) and head length. Mean torque resistances measured were 8.9 N m for a 1 kN test load and 15 N m at 4 kN test load. Coefficients of friction calculated for the torsional stability ranged from 0.06 to greater than 1.0. Multiple regression analysis confirmed that the failure torques measured were significantly dependent on test load (beta = 0.77; P < 0.001) whereas assembly force and head length played a lesser, insignificant, part in the variation. Data from push-on/pull-off tests were used to calculate coefficients of friction under axial loading, which were significantly correlated with taper angle and material. Torque testing shows greater variability than push-on/pull-off tests for similar combinations, and for zirconia heads on other tapers. The coefficients of friction measured (0.16-0.31) are significantly different from values typically used in stress analyses.
Macdonald W, Carlsson LV, Charnley GJ, et al., 1999, Press-fit acetabular cup fixation: principles and testing, Proc Inst Mech Eng [H], Vol: 213, Pages: 33-39, ISSN: 0954-4119
Pre-clinical testing of the fixation of press-fit acetabular components of total hip prostheses relies on cadaver or synthetic bone, but the properties and geometry of bone models differ from those of physiological bone. Cup designs use varied mechanisms for initial stability in bone; therefore, using different analogues and tests is appropriate. Press-fit cup stability was tested in the following: firstly, polyurethane (PU) foam modelling cancellous support; secondly, glass-fibre reinforced epoxide (GFRE) tubes modelling acetabular cortical support; thirdly, cadaveric acetabula. Three commercial cups [Harris-Galante II (H-G-II), Zimmer; Optifix, Smith & Nephew, Richards; porous coated anatomic (PCA), Howmedica] and an experimental cup with enhanced rim fixation were tested in three modes: direct pull-out, lever-out and axial torque. The fixation stabilities measured in the PU and the GFRE models showed trends consistent with those in cadaver bone, differing in the oversizing and cup geometry. The experimental cup was significantly more secure in most modes than other cups; the H-G II and Optifix cups showed similar stabilities, lower than that of the experimental cup but greater than that of the PCA cup (analysis of variance and Tukey's highly significant test; p < 0.001). The stabilities measured in cadaver bone more closely approximated those in GFRE. The use of several bone analogues enables separation of fixation mechanisms, allowing more accurate prediction of in vivo performance.
Macdonald W, Carlsson LV, Charnley GJ, et al., 1999, Inaccuracy of acetabular reaming under surgical conditions, J Arthroplasty, Vol: 14, Pages: 730-737, ISSN: 0883-5403
Press-fit uncemented acetabular components require accurate implant-bone cavity fit. Ten cavities produced during actual hip arthroplasty using debris-retaining reamers were replicated in dental alginate. An experimental reamer with better cutting prepared 12 acetabulae in mortuo under similar conditions. Positives in dental stone were measured on a coordinate measuring center. Spheres of best-fit and variation of each point from these spheres were calculated. Control cavities in polyurethane foam were measured to estimate casting errors. Diametral errors of conventionally reamed cavities averaged 2.1%, whereas experimental reamers' cavities varied by 0.5% (P < .005). Overall surface variation from hemispheric form in conventionally reamed cavities exceeded the experimental reamer's results (P < .005). Conventional acetabular reamers cut bone inaccurately. Reamers designed for improved bone cutting reduce cavity errors.
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