Objectives. Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. Methods. Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays. Results. After six weeks, the area of mineralisation was significantly higher for the transplanted osteophytes than for the cancellous bone (43803 μm. 2. , . sd. 14660 versus 9421 μm. 2. , . sd. 5032, p = 0.0184, one-way analysis of variance). Compared with cancellous bone, the conditioned medium prepared using osteophytes contained a significantly higher amounts of transforming growth factor (TGF)-β1 (471 pg/ml versus 333 pg/ml, p = 0.0001, Wilcoxon rank sum test), bone morphogenetic protein (BMP)-2 (47.75 pg/ml versus 32 pg/ml, p = 0.0214, Wilcoxon rank sum test) and insulin-like growth factor (IGF)-1 (314.5 pg/ml versus 191 pg/ml, p = 0.0418, Wilcoxon rank sum test). The stronger effects of osteophytes towards osteoblasts in terms of a higher proliferation rate, upregulation of gene expression of differentiation markers such as alpha-1 type-1 collagen and alkaline phosphate, and higher migration, compared with cancellous bone, was confirmed. Conclusion. We provide evidence of favourable features of osteophytes for bone mineralisation through a direct effect on osteoblasts. The acceleration in metabolic activity of the osteophyte provides justification for future studies evaluating the clinical use of osteophytes as autologous bone grafts. Cite this article: K. Ishihara, K. Okazaki, T. Akiyama, Y. Akasaki, Y. Nakashima.
Ceramic-on-ceramic (CoC) total hip arthroplasty (THA) can produce articular noise during the normal activities, generating discomfort to the patient. THA noise has to be investigated also as a potential predictor and a clinical sign of prosthetic failure. An observational study has been carried out to characterize the noise in CoC cementless THA, and to analyze the related factors. A total of 46 patients with noisy hip have been enrolled in 38 months, within the follow-up protocol normally applied for the early diagnosis of ceramic liner fracture [1]. Noise recording was based on a high-quality audible recorder (mod. LS 3, Olympus, Japan) and a portable ultrasonic transducer (mod USB AE 1ch, PAC, USA). The sensors for noise recording were applied to the hip of the patient during a sequence of repeatable motorial activities (forward and backward walking, squat, sit in a chair, flexion and extension of the leg). Sessions were also video-recorded to associate the noise emission to the specific movements. Each noise event was initially identified by the operator and therefore classified by comparison to the spectral characteristics (duration, intensity and frequency) of the main noise types. Number and spectral characteristics of noise events were obtained and correlated to the factors describing the clinical status of the patient, the surgical approach, the prosthetic device implanted. The study investigated also the noise as a sign of implant failure, by comparison with the total number of implants failed in the cohort during the study. We observed three types of noise with the main spectral characteristics in agreement to the literature: clicking, squeaking and popping. Among the identified types of noise, squeaking showed the longest duration and the highest amplitude. The 63% of hip presented the emission of just one type of noise, while the remaining a mix of types. The movement with the highest presence of noise was walking, followed by squat. Correlation was found between the noise type and the dimension of the ceramic head (p<0.001), with the sizes of 32 mm more affected by squeaking that the smaller one. Squeaking appeared before during the follow-up than the other types of noise. The 35% (16/46) of the noisy hips were revised during the study. Among the revised hips, the 81% (13/16) were affected by impingement and/or severe damage of the prosthetic components. The antiversion of the cup (p=0.008), the presence of debris in the synovial fluid (p=0.021) and the average frequency of squeaking (p=0.006) were significant predictors for the revision, but it has to be mentioned that the squeaking data was obtained on a small subset of revised patients. Ultrasonic analysis did not show significant correlations. The study presented and validated an experimental procedure to analyze noisy hips in clinical trials. Noise is confirmed to be a significant parameter in the follow-up evaluation of ceramic THA.
Periprosthetic osteolysis is the most common long-term complication of a total joint arthroplasty, often resulting in aseptic loosening of the implant. As we aim at developing a safe and minimally invasive implant refixation procedure, thorough characterisation of the properties of the periprosthetic tissue is needed. In this pilot study, the periprosthetic tissue of eleven patients undergoing hip revision surgery due to aseptic loosening was obtained. Histology, confocal microscopy, atomic force microscopy (AFM) and nanoindentation were performed to structurally and mechanically characterise the tissue. The study was approved by the Medical Ethical Committee of the Leiden University Medical Center.Background
Methods
Injury to the syndesmosis occurs in 10–13% of all operative ankle fractures and there is evidence that both incomplete treatment and malreduction of the syndesmosis can lead to poor clinical outcomes. Much attention has been given to post–operative malreduction documented by computer tomography (CT), however, there is limited data about the intact positioning and relative motion of the native syndesmosis. The aim of this study is to elucidate more detailed information on the position of the fibula in the syndesmosis during simulated weight–bearing in intact state, with sequential ligament sectioning and following two reconstructive techniques. Fourteen paired, fresh–frozen human cadaveric limbs were mounted in a weight–bearing simulation jig. CT scans were obtained under simulated foot–flat loading (75 N) and in single–legged stance (700 N), in five foot positions: neutral, 15° external rotation, 15° internal rotation, 20° dorsiflexion, and 20° plantarflexion. The elements of the syndesmosis and the deltoid ligament were sequentially sectioned. One limb of each pair was then reconstructed via one of two methods: Achilles autograft and peroneus longus ligamentoplasty. The specimens were rescanned in all 5 foot positions following each ligament resection and reconstruction. Measurements of fibular diastasis, rotation and anterior–posterior translation were performed on the axial cuts of the CT scans, 1 cm proximal to the roof of the plafond. Multiple measurements were made to define the position of the fibula in the incisura. Clinically relevant deformity patterns were produced. The deformity at the incisura was consistent with clinical injury, and the degree of displacement in all ligament states was dependent on the foot position. The most destructive state resulted in the most deformity at the syndesmosis. Differences between the intact and reconstructed states were found with all measurements, especially when the foot was in external rotation and dorsiflexion. There was no significant difference with direct comparison of the reconstructions. This study has detailed the motion of the fibula in the incisura and its variation with foot position. Neither reconstruction was clearly superior and both techniques had difficulty in the externally rotated and dorsiflexed foot positions. This study design can serve as a model for future ex–vivo testing of reconstructive techniques.
Besides conventional chondrosarcoma, several rare chondrosarcoma subtypes are described, comprising about 15% of all chondrosarcomas. Clear cell chondrosarcoma (CCS) is a low-grade malignant tumour, often recurring after curettage, and showing overall survival of about 85%. Mesenchymal chondrosarcoma (MCS) is a highly malignant tumour occurring in bone and soft tissue of relatively young patients. The tumour shows differentiated cartilage mixed with undifferentiated small round cells. It often metastasises and shows a 5-year overall survival of 55%. Dedifferentiated chondrosarcoma (DDCS) is a tumour containing a high-grade non-cartilaginous sarcoma (DD), and a usually low-grade malignant cartilage-forming tumour (WD). The prognosis is poor. The lack of efficacious treatment of these rare tumours emphasises the need to learn more about their characteristics and to unravel potential targets for therapy. We constructed tissue microarrays (TMAs) with 2mm cores of 45 DDCS (WD and DD), 24 CCS, and 25 MCS, in triplicate. Using immunohistochemistry, we investigated protein expression of estrogen-signaling molecules, growth plate-signaling molecules, and other molecules which might be potential targets for therapy. In addition, we gathered genomic information using Agilent 44K oligo arrays. 30% of the WD components were positive for Cox-2. Almost all others were negative. For Bcl2, 88% of the small cells and 32% of the cartilage in MCS were positive. In CCS, WD, and DD 48%, 4%, and 12% were positive, respectively. We demonstrated the presence of ESR1 and aromatase protein in the majority of tumours in all subtypes. Using array CGH, we observed similar aberrations in the two components of DDCS, with additional aberrations in the DD. Celecoxib treatment is not recommended, as most of the tumours are negative for Cox-2. However, the presence of ESR1 and aromatase support a possible effect of anti-estrogen treatment in all subtypes, and application of Bcl2 inhibitors might chemosensitise MCS.
Total ankle replacement (TAR) has been used as a surgical intervention for arthritis since the 1970s. However, unlike clinically successful hip and knee replacements, TARs are renowned for extensive contraindications to surgery and high failure rates with an average of 83% survival at 5 years. The majority cite aseptic loosening as the reason for failure. The aim of this study wais to analyse retrieved TARs visually and through interferometry to identify potential the failure mechanisms associated with these devices. Retrieved total ankle replacements (n=11) from consecutive revision surgeries carried out at Chapel Allerton Hospital, Leeds between August 2012 and January 2014, were collected for study at the University of Leeds, under an NRES approved procedure (09/H1307/60). The bearing surfaces of the samples were visually inspected for evidence of damage and wear. The bearing surfaces between the tibial component and the flat surface of the polyethylene insert were then examined using a scanning white light interferometer (NP Flex, Bruker, USA). It was not possible to characterise the talar bearing surface or the inferior polyethylene surface at this stage through interferometry due to the curvature of the surface. The components were aligned and five sections on each of the surfaces measured. These sections represented; anterior-medial, anterior-lateral, posterior-medial, posterior lateral and central regions of the bearing surfaces. 3D roughness values were recorded, and the mean 3D surface roughness compared between implants. Measurements were taken on the medial and lateral aspects of the bearing surfaces to investigate whether damage was location specific. A coefficient of determination was calculated to assess the relationship between implantation time and surface roughness.Introduction
Methods
Tendon cells originate from yet poorly described precursor cells and develop in a particular “niche” close to vascular walls. Several factors have been described to determine this niche such as mechanical stimuli, oxygen tension, composition and structure of the extracellular matrix (ECM). Also, the vasculature is considered to play a crucial role for tendon cell development, yet evidence of how this is accomplished is lacking. In this study we therefore focussed on the endothelium of tendon vessels postulating the existence of a paracellular barrier. By electron microscopy, immunohistochemistry, and RT-PCR we investigated the presence of constituents making up such an endothelial barrier which we subsequently tested for its functionality by tracer injection. Moreover, we performed differentiation experiments into the adipogenic, chondrogenic and osteogenic lineage on tendon derived cells in the presence and absence of serum. Expression levels and activity of matrixmetalloproteinases (MMPs) were assessed by western blot and zymography.Introduction
Materials and Methods
The recent development and use of Calcium Phosphate (CaP) based products as orthopaedic implants has increased the need for the development of a greater understanding of the starting materials inherent properties. Chemical composition and crystal phase greatly influence the final product’s behaviour in the body. By gaining a deeper understanding of these properties, greater control in making tailor-made products can be achieved. Calcium Phosphate based powders of varying CaO: P2O5 ratios were prepared by cold isostatic pressing into compact discs (13 mm diameter x 3.6 mm height) and subsequently sintered at temperatures ranging between 200 to 1140 degrees Celsius for a period of 8 hours. The starting powders had CaO:P2O5 ratios ranging from 1.165 to 1.22. Each composition was analysed for microstructural and associated crystal phase modifications with varying sintering temperatures, by scanning electron microscopy (SEM) and X-ray diffraction (XRD). All compositions were shown by XRD to have an initial starting composition of Hydroxyapatite (HA) and Dicalcium Phosphate Anhydrous (DCPA). With increasing sintering temperatures, it was found that the initial composition readily transformed to beta-tricalcium phosphate(B-TCP) for all of the CaO:P2O5 ratios. However, it was found that the higher CaO:P2O5 ratio materials tended to retain residual HA. Sintering of all powders was found to have a densification effect on the microstructure of these compositions. The sintering behaviour of calcium phosphates is extremely dependent on the CaO:P2O5 ratio of the material, influencing both the crystal as well as microstructural properties of the sintered components. This in-turn will have a strong influence on the behaviour of this biomaterial when placed in-vivo.
This study aimed to characterise and qualitatively grade the severity of the corrosion particles released into the hip joint following taper corrosion. The 26 cases examined were CoC/ABG Modular (n = 13) and ASR/SROM (n = 13). Blood serum metal ion levels were collected before and after revision surgery. The haematoxylin and eosin tissue sections were graded on the presence of fibrin exudates, necrosis, inflammatory cells and corrosion products. The corrosion products were identified based on visible observation and graded on abundance. Two independent observers blinded to the clinical patient findings scored all cases. Elemental analysis was performed on corrosion products within tissue sections. X-Ray diffraction was used to identify crystalline structures present in taper debris.Objectives
Methods
The sealing function of the acetabular labrum is central to the stability of the hip and the health of the joint. Disruption of the labrum has been shown to reduce intra-articular pressure and increase the rate of cartilage consolidation during static loading. Functional activities require movement of the hip through wide ranges of joint motion which disrupt joint congruency, and thus may alter the seal. This study was performed to test the hypothesis that the sealing function of the labrum varies with the position of the hip during functional activities. Six fresh cadaveric hip joint specimens were obtained from donors of average age 45.5 ± 16.1 years (range 25–63 years). Each specimen was dissected free of soft tissue, leaving the capsule and labrum intact, potted in mounting fixtures, and placed in a loading apparatus. Catheters were inserted into the central and peripheral compartments of each hip to allow infusion of fluid and monitoring of compartment pressures via miniature transducers (OMEGA Engineering, Inc). After application of a joint load of 0.50 BW, fluid was introduced into the central compartment at a constant rate until transport was indicated by a rise in pressure within the peripheral compartment. These measurements were performed with each hip placed in 10 functional positions ranging from −5 to 105 degrees of flexion, −5 to 13 degrees of abduction, and −25 to 35 degrees of external rotation simulating the sequential stages of gait, stooping, and pivoting. Motion analysis was performed via reflective marker arrays attached to the femur and pelvis to allow computer visualization of the position of the pelvis and femur using CT reconstructions. In each hip position, we measured the peak pressure (kPA) developed within the central compartment prior to fluid transfer to the peripheral compartment.Introduction:
Methods:
Two calcium phosphate cements, brushite and hydroxyapatite, have been recently developed as bone substitution materials. The brushite cement is biocompatible, resorbable, osteoconductive and injectable since it hardens in physiological conditions. In contrast, hydroxyapatite is less resorbable and is not injectable. However, hydroxyapatite presents a higher strength, which may open the perspective of use in weight-bearing regions of the skeleton subjected to multi-axial stresses. The purpose of this work is a full characterization of the multiaxial elastic and failure behaviour of these two cements in a moist environment. The brushite cement was prepared by mixing three phosphate powders in presence of water. A mixture of monetite and calcite powders in presence of water was used to obtain hydroxyapatite self-setting cement. Cylindrical, hollow specimens (Øext=18mm, Øint=14mm, L=40mm) were manufactured to apply uniaxial and torsional deformations. The specimens were cast with a custom mould, avoiding any machining, and thus, residual stresses. Scanning electron microscopy and x-ray diffraction were used to examine the cement microstructures and to determine their final material phases. An MTS axial-torsional machine was used for all mechanical tests. Compression, tension and torsion tests were performed each on five brushite and five hydroxyapatite specimens under moist conditions. Uniaxial and biaxial extensometers were used to measure the elastic moduli and the Poisson ratio. The brushite cement exhibited failure properties comparable or below those of average human cancellous bone and confirmed its indication as a bone filling material (Brushite failure strength : 1.3±0.3 MPa in tension, 2.9±0.4 MPa in shear and 10.7±2.0 MPa in compression). The hydroxyapatite cement had an order of magnitude larger compressive strength (75±4.2 MPa), comparable tensile (3.5±0.9 MPa) and shear (4.8±0.3 MPa) strengths as average human cancellous bone. As expected, the latter cement seems to be more compatible with a multiaxial weight-bearing function in bone substitution.
The purpose of this study was to identify the factors contributing to the development and progression of periacetabular osteolytic lesions and to identify which of these lesions can progress at an early stage following THA using repeated computed tomography scans. We also evaluated the accuracy of radiographs in assessing periacetabular osteolysis after THA with uncemented acetabular components and compared it with results of CT analysis. CT scans were done in ninety-seven patients (118 hips) who had undergone primary THA between 1996 and 2004 at our hospital at a minimum of two-years postoperatively, from April to August 2006. All the CT images were acquired using high resolution multi-detector row CT (MDCT). The mean age of the patients at the time of surgery was 46.2 years (range, 21–65 years). The mean follow-up at the time of obtaining CT scan was 82.1 months (range, 18–234 months). The second CT scans were obtained in sixty three hips of 49 patients (36 males and 13 females) in 2009. The mean of patient's age was 52.7 years (range, 30 to 76 years). At the time of initial CT scan, the mean duration of implantation was 76.9 months (range, 17–156 months). The volume of periacetabular osteolysis was measured using Rapidia 3D software version. Linear wear of the PE was measured in digitalized radiographs obtained within 3 months of the surgery.Introduction
Methods
A retrospective analysis of 63 primary total hip arthroplasty cases was done using repeated computed tomography scans to evaluate the pelvic osteolytic lesions in early stage. The progression rate of osteolysis of hips with small osteolytic volume less than 766.97 mm(3) in initial CT was 85.82 mm(3)/year, and that of hips with osteolysis more than 766.97 mm(3) was 456.3 mm(3)/year (P < 0.001). Younger patients less than 52 years old with good Harris Hip Scores (more than 80) frequently showed much faster progression in volume of osteolytic lesions. The rate of osteolysis was accelerated when the amount of osteolysis reached a certain threshold volume in active young patients in a cascade manner even in early stage.
Novel hydrogel implants, TRUFIT® bone plugs, have been developed by Smith & Nephew to replace worn-out cartilage surfaces, restoring mobility and relieving joint pain. There is limited information, however, on the biomechanical properties of the implants. Therefore, appropriate mechanical testing and modelling must be carried out to assess their mechanical properties for load bearing applications. In this study, compressive properties of TRUFIT® bone and dual layer implants were examined under selected physiological loading conditions. The bone layer of the implant was also modelled using a biphasic poroviscoelastic (BPVE) material constitutive law and the results from the model are compared with those from the experiments. TRUFIT® CB plugs, with diameters of 11 and 5mm, were sectioned to obtain single layer bone and dual layer samples, with an aspect ratio of 0.86. Specimens were tested in confined and unconfined compressions at two constant strain rates of 0.002/sec (walking) and 0.1/sec (impact) [1-3] on a MTS servo-hydraulic test machine equipped with a bionix envirobath. All samples were tested in phosphate buffered saline (PBS) solution at 37 °C. A preload of 0.1 MPa was applied and preconditioning (10 cycles of 0.008 strain) at a constant strain rate of 0.005 sec−1 [4] was used. The compressive modulus was calculated from the slope of the linear part of the stress-strain curve. In addition, whilst stress relaxation tests were performed on the bone samples in unconfined compression up to 5% strain, at a strain rate of 0.01/s (running) [1-2].Introduction
Materials and Methods
Hyaline cartilage defects are a significant clinical problem for which a plethora of cartilage repair techniques are used. One such technique is cartilage replacement therapy using autologous chondrocyte or mesenchymal stem cell (MSC) implantation (ACI). Mesenchymal stem cells are increasingly being used for these types of repair technique because they are relatively easy to obtain and can be expanded to generate millions of cells. However, implanted MSCs can terminally differentiate and produce osteogenic tissue which is highly undesirable, also, MSCs generally only produce fibrocartilage which does not make biomechanically resilient repair tissue, an attribute that is crucial in high weight-bearing areas. Tissue-specific adult stem cells would be ideal candidates to fill the void, and as we have shown previously in animal model systems [Dowthwaite et al, 2004, J Cell Sci 117;889], they can be expanded to generate hundreds of millions of cells, produce hyaline cartilage and they have a restricted differential potential. Articular chondroprogenitors do not readily terminally differentiate down the osteogenic lineage. At present, research focused on isolating tissue-specific stem cells from articular cartilage has met with modest success. Our results demonstrate that using differential adhesion it is possible to easily isolate articular cartilage progenitor populations from human hyaline cartilage and that these cells can be subsequently expanded in vitro to a high population doubling whilst maintaining a normal karyotype. Articular cartilage progenitors maintain telomerase activity and telomere length that are a characteristic of progenitor/stem cells and differentiate to produce hyaline cartilage. In conclusion, we propose the identification and characterisation of a novel articular cartilage progenitor population, resident in human cartilage, which will greatly benefit future cell-based cartilage repair therapies.
Aim of the study was to evaluate if abrasion-arthroplasty (AAP) and abrasion-chondroplasty (ACP) leads to a release of mesenchymal stem cell (MSC) like cells from the bone marrow to the joint cavity where they probably differentiate into a chondrogenic phenotype. Cartilage demage is a sever problem in our aging society. About 5 million people only in Germany are affected. Osteoathritis is a degeneration of cartilage caused by aging or traumata 50 % of the people over 40 have signs of osteoarthritis. But the ability of self-regeneration of cartilage is strongly limited. There are different approaches to therapy osteoathritic lesions. Arthroscopic treatment of OA includes bone marrow stimulation technique such as abrasion arthroplasty (AAP) and microfracturing (MF). Beside the support of chondrocyte progenitor cells the environment is also important for the commitment to chondrocytes. Therefore insulin-like growth factor-1 (IGF-1) and transforming growth factor beta-1 (TGF-β1) are important factors during the regeneration process. In the present study we characterised the heamarthrosis and the released cells after AAP and its ability to differentiate into the chondrocyte lineage. Postoperative haemarthrosis was taken 5, 22 or 44 hours after surgery. 7.5 mg Dexamethasone (Corticosteroid) was administered into the knee joint to prevent postoperative inflammation. Mononuclear cells were isolated from haemarthrosis from the drainage bottle by ficoll density gradient centrifugation. The isolated cells were characterised using fluorescence-activated cell-sorting (FACS) analysis for characteristic markers of MSC such as CD 44, 73, 90, 105. After expanding cells were cultured in a pellet culture. After 3 weeks, histochemistry and immunohistochemistry against Sox9, collagen II and proteoglycan were performed. The release of IGF1, BMP4 and BMP7 was analysed in haemarthrosis serum by ELISA and Luminex technology.Introduction
Material and Methods
Injectable scaffolds which also deliver cells and bioactive molecules to augment bone healing overcome many of the limitations associated with current bone graft substitutes. The aim of this study was to develop and test a novel injectable scaffold that self-assembles isothermically in situ to form a biodegradable porous osteoconductive material, and to assess the viability of human mesenchymal stem cells (hMSC) seeded onto the scaffold. Rheological assessment was performed on three different molecular weights (Mw) of poly(lactic-co-glycolic acid) (PLGA) (26kDa, 53kDa and 92kDa) combined with differing ratios of polyethylene glycol (PEG) to control the temperature required for scaffold self-assembly. The strength (MPa) and stiffness (Young's Modulus) patterns of the scaffolds were assessed in compression. The cell viability, proliferation and distribution patterns of hMSCs seeded within the scaffold were assessed through various assays (Alamar Blue), confocal microscopy and micro-CT. The hMSC differentiation in osteogenic media was characterised by the identification of specific bone formation markers (e.g. alkaline phosphatase).Background/Study Aim
Methods
One hundred and four invasive Aim
Method
Our objective in this article is to test the hypothesis that
type 2 diabetes mellitus (T2DM) is a factor in the onset and progression
of osteoarthritis, and to characterise the quality of the articular
cartilage in an appropriate rat model. T2DM rats were obtained from the UC Davis group and compared
with control Lewis rats. The diabetic rats were sacrificed at ages
from six to 12 months, while control rats were sacrificed at six
months only. Osteoarthritis severity was determined via histology
in four knee quadrants using the OARSI scoring guide. Immunohistochemical
staining was also performed as a secondary form of osteoarthritic
analysis.Objectives
Methods
