UCL Institute of Orthopaedics and Musculoskeletal Science
UCL Institute of Orthopaedics and Musculoskeletal Science
Magdeldin T.,UCL Institute of Orthopaedics and Musculoskeletal science |
Magdeldin T.,University College London |
Lopez-Davila V.,University College London |
Pape J.,UCL Institute of Orthopaedics and Musculoskeletal science |
And 4 more authors.
Scientific Reports | Year: 2017
The hallmark of tumours is the ability of cancerous cells to promote vascular growth, to disseminate and invade to distant organs. The metastatic process is heavily influenced by the extracellular matrix (ECM) density and composition of the surrounding tumour microenvironment. These microenvironmental cues, which include hypoxia, also regulate the angiogenic processes within a tumour, facilitating the spread of cancer cells. We engineered compartmentalized biomimetic colorectal tumouroids with stromal surrounds that comprised a range of ECM densities, composition and stromal cell populations. Recapitulating tissue ECM composition and stromal cell composition enhanced cancer cell invasion. Manipulation of ECM density was associated with an altered migration pattern from glandular buds (cellular aggregates) to epithelial cell sheets. Laminin appeared to be a critical component in regulating endothelial cell morphology and vascular network formation. Interestingly, the disruption of vascular networks by cancer cells was driven by changes in expression of several anti-angiogenic genes. Cancer cells cultured in our biomimetic tumouroids exhibited intratumoural heterogeneity that was associated with increased tumour invasion into the stroma. These findings demonstrate that our 3D in vitro tumour model exhibits biomimetic attributes that may permit their use in studying microenvironment clues of tumour progression and angiogenesis. © The Author(s) 2017.
Abou Neel E.A.,King Abdulaziz University |
Abou Neel E.A.,Tanta University |
Abou Neel E.A.,University College London |
Bozec L.,University College London |
And 6 more authors.
Advanced Drug Delivery Reviews | Year: 2013
The choice of biomaterials available for regenerative medicine continues to grow rapidly, with new materials often claiming advantages over the short-comings of those already in existence. Going back to nature, collagen is one of the most abundant proteins in mammals and its role is essential to our way of life. It can therefore be obtained from many sources including porcine, bovine, equine or human and offer a great promise as a biomimetic scaffold for regenerative medicine. Using naturally derived collagen, extracellular matrices (ECMs), as surgical materials have become established practice for a number of years. For clinical use the goal has been to preserve as much of the composition and structure of the ECM as possible without adverse effects to the recipient. This review will therefore cover in-depth both naturally and synthetically produced collagen matrices. Furthermore the production of more sophisticated three dimensional collagen scaffolds that provide cues at nano-, micro- and meso-scale for molecules, cells, proteins and bulk fluids by inducing fibrils alignments, embossing and layered configuration through the application of plastic compression technology will be discussed in details. This review will also shed light on both naturally and synthetically derived collagen products that have been available in the market for several purposes including neural repair, as cosmetic for the treatment of dermatologic defects, haemostatic agents, mucosal wound dressing and guided bone regeneration membrane. There are other several potential applications of collagen still under investigations and they are also covered in this review. © 2012 Elsevier B.V.
Korda M.,UCL Institute of Orthopaedics and Musculoskeletal Science |
Hua J.,UCL Institute of Orthopaedics and Musculoskeletal Science |
Little N.J.,Waikato Hospital |
Heidari N.,University of Essex |
Blunn G.W.,UCL Institute of Orthopaedics and Musculoskeletal Science
Tissue Engineering - Part A | Year: 2010
Revision total hip replacement has a failure rate of up to 25%. Part of the reason for this high failure is the lack of bone stock. In this study, we investigated whether mesenchymal stromal cells (MSCs) or osteoprogenitors (OPs) contribute to bone formation in impacted allograft or an allograft and hydroxyapatite (HA) combination. Eight samples were inserted in the paraspinal muscles of six sheep, which were allograft or an HA/allograft mix, seeded with autologous MSCs, autologous OPs, or no cells (control), and impacted with a clinically relevant force at 3kN preimplantation. Other groups were HA blocks seeded with or without MSCs. Samples were retrieved at 12 weeks. MSCs incorporated into allograft, HA/allograft, and HA blocks displayed higher mean values of new bone formation compared with the controls, but there was no statistical difference between allograft groups. However, in HA/allograft groups, significantly more new bone was found with MSCs than without cells (p=0.046) or with OPs (p=0.028). In the HA blocks, more new bone was found in the MSC group than in the HA block without cells (p=0.028). In conclusion, MSCs used with combinations of allograft and HA enhance new bone formation in an ovine ectopic site after being subjected to realistic forces that are used during impaction grafting. Copyright 2010, Mary Ann Liebert, Inc.
Goldberg A.J.,Royal National Orthopaedic Hospital NHS Trust |
MacGregor A.,Royal National Orthopaedic Hospital NHS Trust |
Spencer S.A.,UCL Institute of Orthopaedics and Musculoskeletal Science |
Spencer S.A.,Information Center
Journal of Bone and Joint Surgery - Series B | Year: 2012
With the established success of the National Joint Registry and the emergence of a range of new national initiatives for the capture of electronic data in the National Health Service, orthopaedic surgery in the United Kingdom has found itself thrust to the forefront of an information revolution. In this review we consider the benefits and threats that this revolution poses, and how orthopaedic surgeons should marshal their resources to ensure that this is a force for good. ©2012 British Editorial Society of Bone and Joint Surgery.
Hao S.,UCL Institute of Orthopaedics and Musculoskeletal Science |
Taylor J.,University of Bath
Sensors and Transducers | Year: 2013
This paper describes the optimization of a set of initial parameter values in an implantable, remotely interrogated electronic displacement sensor for use in applications of such as implants for total hip and total knee arthroplasty. This is the first reported implantable electronic system capable of satisfactorily measuring both postoperative migration and micromotion. In earlier reported work by the same authors, the initial parameter values of the differential variable reluctance transducer (DVRT), which is the key component of the system, were chosen somewhat randomly and were not optimal. In this short paper, the influence of the initial resistance and coil parameters in the bridge on the operation of the DVRT is explored in terms of the accuracy, resolution, detection range of the measurement and the coil size. © 2013 IFSA.
Faroug R.,UCL Institute of Orthopaedics and Musculoskeletal Science |
McCarthy I.,UCL Institute of Orthopaedics and Musculoskeletal Science |
McCarthy I.,Royal National Orthopaedic Hospital |
Meswania J.,UCL Institute of Orthopaedics and Musculoskeletal Science |
And 3 more authors.
Journal of Medical Engineering and Technology | Year: 2011
Objectives: An experimental biomechanical evaluation of an instrumented intramedullary nail (TriGen® META Nail, Smith&Nephew®) was undertaken. The objectives were two-fold. The first was to identify the most sensitive strain gauge positions and orientations on the nail, and the second was to demonstrate that the nail was capable of detecting changes in stiffness of the nail-bone composite. The function of the instrumented nail is to quantify fracture healing objectively and directly, and so to predict delayed repair or non-union 2 months before current methods. Methods: Eight flat pockets were machined onto the surface of the nail and three strain gauges attached in each pocket. The instrumented nail was inserted into fourth generation biomechanical grade Sawbones® tibiae with three different fracture configurations as well as into a non-fractured bone. The nailâ€"bone composite was loaded in three-point bending at five positions to determine the strain changes in each of the eight strain gauge pockets located along the length of the nail. To simulate callus in the simplest way and to increase the stiffness of the nail-bone composite, loops of duct tape in multiples of four were applied over the fracture locus. A three-point loading jig was used to obtain the change in strain with increasing stiffness. Relative displacement of the bone ends was quantified using radiostereometric analysis. Results: There was no single position of greatest strain sensitivity for all fracture types. The greatest change in strain occurred when the strain gauge pocket and fracture line were closest. Applying the loading moment directly over the strain gauge pocket also maximised its sensitivity. The duct tape callus simulation showed that the instrumented nail was able to detect a change in stiffness of less than 4.1 Nm/°. Conclusions: It has been shown that the instrumented nail can detect physiologically relevant changes in stiffness, and so to provide a useful function as an objective monitor of fracture repair. © 2011 Informa UK, Ltd.
Player D.J.,Loughborough University |
Martin N.R.W.,Loughborough University |
Passey S.L.,Loughborough University |
Passey S.L.,University of Melbourne |
And 4 more authors.
Biotechnology Letters | Year: 2014
Skeletal muscle (SkM) is a tissue that responds to mechanical load following both physiological (exercise) or pathophysiological (bed rest) conditions. The heterogeneity of human samples and the experimental and ethical limitations of animal studies provide a rationale for the study of SkM plasticity in vitro. Many current in vitro approaches of mechanical loading of SkM disregard the three-dimensional (3D) structure in vivo. Tissue engineered 3D SkM, that displays highly aligned and differentiated myotubes, was used to investigate mechano-regulated gene transcription of genes implicated in hypertrophy/atrophy. Static loading (STL) and ramp loading (RPL) at 10 % strain for 60 min were used as mechano-stimulation with constructs sampled immediately for RNA extraction. STL increased IGF-I mRNA compared to both RPL and CON (control, p = 0.003 and 0.011 respectively) whilst MMP-9 mRNA increased in STL and RPL compared to CON (both p < 0.05). IGFBP-2 mRNA was differentially regulated in RPL and STL compared to CON (p = 0.057), whilst a reduction in IGFBP-5 mRNA was found for STL and RPL compared to CON (both p < 0.05). There was no effect in the expression of putative atrophic genes, myostatin, MuRF-1 and MAFBx (all p > 0.05). These data demonstrate a transcriptional signature associated with SkM hypertrophy within a tissue-engineered model that more greatly recapitulates the in vivo SkM structure compared previously published studies. © 2014 Springer Science+Business Media Dordrecht.
Gibbons R.S.,Brunel University |
McCarthy I.D.,UCL Institute of Orthopaedics and Musculoskeletal Science |
Gall A.,UCL Institute of Orthopaedics and Musculoskeletal Science |
Gall A.,Royal National Orthopaedic Hospital |
And 3 more authors.
Spinal Cord | Year: 2014
Study design: A single case study. Objectives: To compare proximal tibia trabecular bone mineral density (BMD) of a participant with complete spinal cord injury (SCI), long-termed functional electrical stimulation-rowing (FES-R) trained, with previously reported SCI and non-SCI group norms. To estimate lower limb joint contact forces (JCFs) in the FES-R trained participant. Setting: UK University and orthopaedic hospital research centre. Methods: Bilateral proximal tibial trabecular BMD of the FES-R trained participant was measured using peripheral quantitative computerised tomography, and the data were compared with SCI and non-SCI groups. An instrumented four-channel FES-R system was used to measure the lower limb JCFs in the FES-R trained participant. Results: Structurally, proximal tibial trabecular BMD was higher in the FES-R trained participant compared with the SCI group, but was less than the non-SCI group. Furthermore, left (184.7 mg cm-3) and right (160.7 mg cm-3) BMD were well above the threshold associated with non-traumatic fracture. The knee JCFs were above the threshold known to mediate BMD in SCI, but below threshold at the hip and ankle. Conclusion: As pathological fractures predominate in the distal femur and proximal tibia in chronic SCI patients, the fact that the FES-R trained participant's knee JCFs were above those known to partially prevent bone loss, suggests that FES-R training may provide therapeutic benefit. Although the elevated bilateral proximal tibial BMD of the FES-R participant provides circumstantial evidence of osteogenesis, this single case precludes any statement on the clinical significance. Further investigations are required involving larger numbers and additional channels of FES to increase loading at the hip and ankle. © 2014 International Spinal Cord Society All rights reserved.
PubMed | UCL Institute of Orthopaedics and Musculoskeletal Science
Type: Journal Article | Journal: Spinal cord | Year: 2012
A cross-sectional study.To measure the change of structural and material properties at different sites of the tibia in spinal cord-injured patients using peripheral quantitative computerised tomography (pQCT).Orthopaedic research centre (UK).Thirty-one subjects were measured--eight with acute spinal cord injury (SCI), nine with chronic SCI and fourteen able-bodied controls. pQCT scans were performed at 2% (proximal), 34% (diaphyseal) and 96% (distal) along the tibia from the tibial plateau. Structural measures of bone were calculated, and volumetric bone mineral density (vBMD) was also measured at all three levels. Muscle cross-sectional area was measured at the diaphyseal level.Structurally, there were changes in the cortical bone; in the diaphysis, the shape of the cross-section changed to offer less resistance to AP bending, and the cross-sectional area of the cortical shell decreased both proximally and distally. There were corresponding changes in vBMD in the anterior aspect of the cortical diaphysis, as well as proximal and distal trabecular bone. Changes in muscle occurred more rapidly than changes in bone.There were clear changes of both structure and material at all three levels of the tibia in chronic SCI patients. These changes were consistent with specific adaptations to reduced local mechanical loading conditions. To assess fracture risk in SCI and also to monitor the effect of therapeutic interventions, the structure of the bone should be considered in addition to trabecular bone mineral density.
PubMed | UCL Institute of Orthopaedics and Musculoskeletal Science, Coventry University, University of Oxford, University College London and Brunel University
Type: | Journal: Spinal cord | Year: 2014
A single case study.To compare proximal tibia trabecular bone mineral density (BMD) of a participant with complete spinal cord injury (SCI), long-termed functional electrical stimulation-rowing (FES-R) trained, with previously reported SCI and non-SCI group norms. To estimate lower limb joint contact forces (JCFs) in the FES-R trained participant.UK University and orthopaedic hospital research centre.Bilateral proximal tibial trabecular BMD of the FES-R trained participant was measured using peripheral quantitative computerised tomography, and the data were compared with SCI and non-SCI groups. An instrumented four-channel FES-R system was used to measure the lower limb JCFs in the FES-R trained participant.Structurally, proximal tibial trabecular BMD was higher in the FES-R trained participant compared with the SCI group, but was less than the non-SCI group. Furthermore, left (184.7mgcm(-3)) and right (160.7mgcm(-3)) BMD were well above the threshold associated with non-traumatic fracture. The knee JCFs were above the threshold known to mediate BMD in SCI, but below threshold at the hip and ankle.As pathological fractures predominate in the distal femur and proximal tibia in chronic SCI patients, the fact that the FES-R trained participants knee JCFs were above those known to partially prevent bone loss, suggests that FES-R training may provide therapeutic benefit. Although the elevated bilateral proximal tibial BMD of the FES-R participant provides circumstantial evidence of osteogenesis, this single case precludes any statement on the clinical significance. Further investigations are required involving larger numbers and additional channels of FES to increase loading at the hip and ankle.