Aims

To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

Osteoarthritis, the most common degenerative joint disease, significantly impairs life quality and labor capability of patients. Synovial inflammation, initiated by HMGB1 (High mobility group box 1)-induced activation of macrophage, precedes other pathological changes. As an upstream regulator of NF-κB (nuclear factor-kappa B) and MAPK (mitogen-activated protein kinase) signaling pathway, TAK1 (TGF-β activated kinase 1) participates in macrophage activation, while its function in osteoarthritis remains unveiled. This study aims to investigate the role of TAK1 in the pathogenesis of osteoarthritis via both in vitro and in vivo approaches.

We performed immunohistochemical staining for TAK1 in synovial tissue, both in osteoarthritis patients and healthy control. Besides, immunofluorescence staining for F4/80 as macrophage marker and TAK1 were conducted as well. TAK1 expression was examined in RAW264.7 macrophages stimulated by HMGB1 via qPCR (Quantitative polymerase chain reaction) and Western blotting, and the effect of TAK1 inhibitor (5z-7 oxozeaenol) on TNF-α production was evaluated by immunofluorescence staining. Further, we explored the influence of intra-articular shRNA (short hairpin RNA) targeting TAK1 on collagenase-induced osteoarthritis in mice.

Immunohistochemical staining confirmed significant elevation of TAK1 in osteoarthritic synovium, and immunofluorescence staining suggested macrophages as predominant residence of TAK1. In HMGB1-stimulated RAW264.7 macrophages, TAK1 expression was up-regulated both in mRNA and protein level. Besides, TAK1 inhibitor significantly impairs the production of TNF-α by macrophages upon HMGB1 stimulation. Moreover, intra-articular injection of lentivirus loaded with shRNA targeting TAK1 (sh-TAK1) reduced peri-articular osteophyte formation in collagenase-induced osteoarthritis in mice.

TAK1 exerts a potent role in the pathogenesis of osteoarthritis by mediating the activation of macrophages.

Intervertebral disc degeneration can lead to physical disability and significant pain, while the present therapeutics still fail to biochemically and biomechanically restore the tissue. Stem cell-based therapy in treating intervertebral disc (IVD) degeneration is promising while transplanting cells alone might not be adequate for effective regeneration. Recently, gene modification and 3D-printing strategies represent promising strategies to enhanced therapeutic efficacy of MSC therapy. In this regard, we hypothesized that the combination of thermosensitive chitosan hydrogel and adipose derived stem cells (ADSCs) engineered with modRNA encoding Interleukin − 4 (IL-4) can inhibit inflammation and promote the regeneration of the degenerative IVD.

Rat ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IL-4 modRNA engineered ADSCs (named as IL-4-ADSCs) on nucleus pulposus cells.

ModRNA transfected mouse ADSCs with high efficiency and the IL-4 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IL-4 protein. In vitro, IL-4-ADSCs induced increased anabolic markers expression of nucleus pulposus cells in inflammation environment compared to untreated ADSCs.

These findings collectively supported the therapeutic potential of the combination of thermosensitive chitosan hydrogel and IL-4-ADSCs for intervertebral disc degeneration management. Histological and in vivo validation are now being conducted.

Quantitative ultrasound (QUS) is a promising tool to estimate bone structure characteristics and predict fragile fracture. The aim of this pilot cross-sectional study was to evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragile fractures retrospectively in postmenopausal women.

Total joint replacement (TJR) was one of the most revolutionary breakthroughs in joint surgery. The majority studies had shown that most implants could last about 25 years, anyway, there is still variation in the longevity of implants. In US, for all the hip revisions from 2012 to 2017 in the United States, 12.0% of the patients were diagnosed as aseptic loosening. Variable studies have showed that any factor that could cause a systemic or partial bone loss, might be the risk of periprosthetic osteolysis and aseptic loosening.

Breast cancer is the most frequent malignancy in women, more than 2.1 million women were newly diagnosed with breast cancer, 626,679 women with breast cancer died in 2018. It's been reported that the mean incidence of THA was 0.29% for medicare population with breast cancer in USA, of which the incidence was 3.46% in Norwegian. However, the effects of breast cancer chemotherapy and hormonotherapy, such as aromatase inhibitors (AI), significantly increased the risk of osteoporosis, and had been proved to become a great threat to hip implants survival.

In this case, a 46-year-old female undertook chemotherapy and hormonotherapy of breast cancer 3 years after her primary THA, was diagnosed with aseptic loosening of the hip prosthesis. Her treatment was summarized and analyzed.

Breast cancer chemotherapy and hormonotherapy might be a threat to the stability of THA prosthesis. More attention should be paid when a THA paitent occurred with breast cancer. More studies about the effect of breast cancer treatments on skeleton are required.

As peri-prosthetic aseptic loosening is one of the main causes of implant failure, inhibiting wear particles induced macrophages inflammation is considered as a promising therapy for AL to expand the lifespan of implant. Here, we aim at exploring the role of p110δ, a member of class IA PI3K family, and Krüppel-like factor 4 (KLF4) in titanium particles (TiPs) induced macrophages-inflammation and osteolysis.

Firstly, IC87114, the inhibitor of p110δ and siRNA targeting p110δ were applied and experiments including ELISA and immunofluorescence assay were conducted to explore the role of p110δ. Sequentially, KLF4 was predicted as the transcription factor of p110δ and the relation was confirmed by dual luciferase reporter assay. Next, assays including RT-PCR, western blotting and flow cytometry were performed to ensure the specific role of KLF4. Finally, TiPs-induced mice cranial osteolysis model was established, and micro-CT scanning and immunohistochemistry assay were performed to reveal the role of p110δ and KLF4 in vivo.

Here, we found that p110δ was upregulated in TiPs-stimulated macrophages. The inhibition of p110δ or knockdown of p110δ could significantly dampen the TiPs-induced secretion of TNFα and IL-6. Further mechanistic studies confirmed that p110δ was responsible for TNFα and IL-6 trafficking out of Golgi complex without affecting their expression in TiPs-treated macrophages. Additionally, we explored the upstream regulators and confirmed that Krüppel-like factor 4 (KLF4) was the transcription repressor of p110δ. Apart from that, KLF4, targeted by miR-92a, could also attenuate TiPs-induced inflammation by mediating NF-κB pathway and M1/M2 polarization. By the establishment of TiPs-induced mice cranial osteolysis model, we found that KLF4 knockdown exacerbated TiPs-induced osteolysis which was strikingly ameliorated by knockdown of p110δ.

In summary, our study suggests the key role of miR-92a/KLF4/p110δ signal in TiPs-induced macrophages inflammation and osteolysis.

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Aims

Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH.

Aims

The aim of this meta-analysis was to assess the prognosis after early functional rehabilitation or traditional immobilization in patients who underwent operative or nonoperative treatment for rupture of the Achilles tendon.

To explore a novel machine learning model to evaluate the vertebral fracture risk using Decision Tree model and train the model by Bone Mineral Density (BMD) of different compartments of vertebral body.

We collected a Computed Tomography image dataset, including 10 patients with osteoporotic fracture and 10 patients without osteoporotic fracture. 40 non-fracture Vertebral bodies from T11 to L5 were segmented from 10 patients with osteoporotic fracture in the CT database and 53 non-fracture Vertebral bodies from T11 to L5 were segmented from 10 patients without osteoporotic fracture in the CT database. Based on the biomechanical properties, 93 vertebral bodies were further segmented into 11 compartments: eight trabecular bone, cortical shell, top and bottom endplate. BMD of these 11 compartments was calculated based on the HU value in CT images.

Decision tree model was used to build fracture prediction model, and Support Vector Machine was built as a compared model. All BMD data was shuffled to a random order. 70% of data was used as training data, and 30% left was used as test data. Then, training prediction accuracy and testing prediction accuracy were calculated separately in the two models.

The training accuracy of Decision Tree model is 100% and testing accuracy is 92.14% after trained by BMD data of 11 compartments of the vertebral body. The type I error is 7.14% and type II error is 0%. The training accuracy of Support Vector Machine model is 100% and the testing accuracy is 78.57%. The type I error is 17.86% and type II error is 3.57%.

The performance of vertebral body fracture prediction using Decision Tree is significantly higher than using Support Vector Machine. The Decision Tree model is a potential risk assessment method for clinical application. The pilot evidence showed that Decision Tree prediction model overcomes the overfitting drawback of Support Vector Machine Model. However, larger dataset and cohort study should be conducted for further evidence.

Aims

Whether to perform hybrid surgery (HS) in contrast to anterior cervical discectomy and fusion (ACDF) when treating patients with multilevel cervical disc degeneration remains a controversial subject. To resolve this we have undertaken a meta-analysis comparing the outcomes from HS with ACDF in this condition.

Objectives

The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility.

Objectives

Irrigation is the cornerstone of treating skeletal infection by eliminating pathogens in wounds. A previous study shows that irrigation with normal saline (0.9%) and ethylenediaminetetraacetic acid (EDTA) could improve the removal of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) compared with normal saline (NS) alone. However, it is still unclear whether EDTA solution is effective against infection with drug-resistant bacteria.

Aim

Radiologic signs such as radiolucent lines around the implant, hardware fracture or displacement and periosteal reaction have been considered suggestive of implant-associated infection. The goal of this study is to assess the correlation of these signs with confirmed internal fixation-associated infection evaluated in a prospective cohort.

Aim

Unexpected positive infections are distinct entity in prosthetic revision surgery. The prevalence and characteristics of unexpected positive cultures in internal fixation are however less established. The aim of this study was to describe the prevalence and characteristics of unexpected diagnosis of infection in a prospective cohort of revision surgeries following internal fixation.

Although single-stage revision has attracted a lot of attention due to less socioeconomic cost, this technique is not widely used throughout the world due to strict indications. In this situation, we report our outcome on single-stage revision combined with selective direct intra-articular antibiotic infusion for chronic infected THA, especially for patients with culture-negative hip, fungal infections and multidrug-resistant organism.

We retrospectively reviewed 131 patients with chronic infected THA between January 2010 and February 2017 who underwent single-stage revision, including soakage of surgical area with 0.5% aqueous betadine, pouring powdered vancomycin or imipenem into the medullary cavity. For patients with culture-negative hip, fungal infections and multidrug-resistant organism, a direct intra-articular infusion of pathogens-sensitive antibiotics via three-branch catheter were performed postoperatively. Recurrence of infection and clinical outcomes were evaluated.

One hundred and fifteen patients were followed-up for an average of 4.5 years (range, 1.2–8 years). Of the 115 patients, 103 patients (89.6%) required no additional surgical or medical treatment for recurrence of infection. A recurrent infection was observed in 4 of the 23 patients (17.4%) with culture-negative infected hip. One of 4 fungal infections was relapse and the success rate in patients with multidrug-resistant organism was 84.2% (16/19). The mean postoperative Harris hip score was 81 points (63 to 92; p < 0.05) at the most recent assessment.

Treatment of chronic infected THA by single-stage revision combined with selective direct intra-articular antibiotic infusion can be fairly effective, even for patients with relative “contraindication” of this approach.

Infection is a potentially disastrous complication of total knee arthroplasty (TKA). Although advances in surgical technique and antibiotic prophylaxis have reduced the incidence of infection to approximately 1% in primary TKA, there is still a substantial number of patients. Treatment options include antibiotic suppression, irrigation and debridement with component retention (with or without polyethylene exchange), one-stage or two-stage revision, resection arthroplasty and rarely arthrodesis or amputation. Salvage of prostheses has always been associated with low rates of success. It was reported a success rate of 27% for open debridement. It is suitable for selective cases where infection occurs within the first 4–6 weeks of primary TKA or in the setting of acute hematogenous gram positive infection with stable implants. With the advances in arthroscopic technique, arthroscopy after TKA has become an accepted method to assess and manage the complications of TKA. Arthroscopic treatment for infected TKA was reported and the successful rate was similar or better than open debridement in selected situations. We used arthroscopic debridement combined with continuous antibiotic irrigation and suction to treat acute presentation of infected TKA with acceptable result. From 2010∼2013, we has performed arthroscopic debridement and continuous antibiotic irrigation system for seven patients with infected TKA. All of the seven patients had no open wounds nor sinuses and no radiological evidence of prosthetic instability or evidence of osteomyelitis. Most of the surgical intervention was performed within two weeks from the onset of symptoms. Arthroscopic debridement was performed with a shaver using a multiportal technique (anterolateral, anteromedial, superolateral, superomedial, posterolateral, posteromedial) and a continuous antibiotic irrigation system was used to dilutes concentration of the causative microorganism and keep high local bactericidal concentration of antibiotics. We evaluated the efficacy by using follow up of the C-reactve protein (CRP) test, erythrocyte sedimentation rate (ESR) test and physical examination. Successful treatment was defined as prosthesis retention without recurrent infection by the final follow-up. Six of seven infected TKA were cured without recurrence at a mean follow-up of 23 months (range, 6–41 months). One case with rheumatoid arthritis under long-term steroid therapy had recurred after episode of upper respiratory tract infection for 3 times. However, the infection was controlled by arthroscopic debridement and retention of the prosthesis was achieved. We emphasize the importance of posterior portal to ensure adequate arthroscopic debridement. It is imperative to make early diagnosis and treatment for infected TKA. We should make more effort to preserve the prosthesis in acute infection(within 2 weeks). With the advantage of minimal morbidity, arthroscopic treatement shoulder be an alternative to open debridement.

Implant-related infection (IRI) is closely related to the local immunity of peri-implant tissues. The generation of reactive oxygen species (ROS) in activated macrophages plays a prominent role in the innate immune response. In previous studies, we indicated that implant wear particles promote endotoxin tolerance by decreasing the release of proinflammatory cytokines. However, it is unclear whether ROS are involved in the damage of the local immunity of peri-implant tissues. In the present study, we assessed the mechanism of local immunosuppression using titanium (Ti) particles and/or lipopolysaccharide (LPS) to stimulate RAW 264.7 cells. The results indicate that the Ti particles induced the generation of a moderate amount of ROS through nicotinamide adenine dinucleotide phosphate oxidase-1 (NOX-1), but not through catalase. Pre-exposure to Ti particles inhibited ROS generation and extracellular regulated protein kinase (ERK) activation in LPS-stimulated macrophages. These findings indicate that chronic stimulation by Ti particles may lead to a state of oxidative stress and persistent inflammation, which may result in the attenuation of the immune response of macrophages to bacterial components such as LPS. Eventually, immunosuppression develops in peri-implant tissues, which may be a risk factor for IRI.

Summary Statement

This study demonstrated that Sclerostin monoclonal antibody (Scl-Ab) enhanced bone healing in the rat osteotomy model. Scl-Ab increased callus size, callus bone volume fraction, rate of callus bone formation and fracture callus strength.

INTRODUCTION:

The use of tapered junctions in primary hip arthroplasty has excellent results. Large heads are being used to mitigate dislocation and optimize range of motion. The prevalence of larger heads, coupled with recent findings regarding corrosion artifacts at tapered surfaces, has spurred growing interest when considering revision rates. The purpose of this study was to determine if correlations exist between severity of corrosion artifacts and head size, head offset, time in vivo, orhead material in a 15 year retrieval database.

INTRODUCTION

One of the recent advances in the hard-on-hard hip arthroplasty is the development of a new material of diffusion hardened oxidised zirconium (DHOxZr). The DHOxZr material consists of a ceramic layer on the top surface which is supported by a thick oxygen diffusion hardened (DH) zone underneath. With the desired properties of metal substrate, ceramic surface and a gradient structure of the oxygen diffusion zone, the DHOxZr-on-DHOxZr bearing combination is expected to produce low wear and minimal metal ions. This can possibly address the concerns associated with metal hypersensitivity associated with metal on metal bearings and fracture risk associated with ceramics. The aim of this study was to evaluate the wear of DHOxZr-on-DHOxZr as a possible hard on hard bearing combination in hips.

INTRODUCTION

Hip wear simulator test results could be affected by many non-bearing related factors such as fixation surface conditions, equipment calibration and component set-up. In an effort to improve the accuracy, reliability and repeatability of hip simulator test, a quality management system has been established at the IDC hip tribology laboratory, which has been accredited by UKAS (United Kingdom Accreditation Service) in accordance with the recognised international standard ISO17025. This study demonstrates that under well-controlled laboratory and testing conditions, satisfactory repeatability can be achieved during hip simulator studies.

Purpose

Angiogenesis and osteogenesis are essential for bone growth, fracture repair, and bone remodeling. VEGF has an important role in bone repair by promoting angiogenesis and osteogenesis. In our previous study, endothelial progenitor cells (EPCs) promoted bone healing in a rat segmental bone defect as confirmed by radiological, histological and microCT evaluations (Atesok, Li, Schemitsch 2010); EPC treatment of fractures resulted in a significantly higher strength by biomechanical examination (Li, Schemitsch 2010). In addition, cell-based VEGF gene transfer has been effective in the treatment of segmental bone defects in a rabbit model (Li, Schemitsch et al 2009); Purpose of this study: Evaluation of VEGF gene expression after EPC local therapy for a rat segmental bone defect.

INTRODUCTION

Whilst there is a great deal of research on hip implants, few studies have looked at implant orientation and the subsequent effect upon the wear performance of a hip resurfacing. This study aimed to measure implantation angles through radiographic analysis and linear wear for retrieved acetabular cups in order to investigate possible causal links between wear and implant orientation.

Introduction

Ion analysis has been used as one of the key indicators to assess the performance of MoM devices in patients. Modular devices, in particular having larger overall surface area (the stem and sleeve), and locking interfaces (head – bore, sleeve- taper and sleeve-bore, stem-taper surfaces) than other MoM devices are expected to release greater number of ions. Concerns have been expressed that the ion release at the taper junction might be a potential cause leading to the failure of the implant [Garbuz et al, 2010].

The aim of this study was to look into the wear and the associated ion release from the taper junction and the articulating surface of modular devices.

INTRODUCTION

Analysis of retrieved ceramic components have shown areas of localized ‘stripe wear’, which have been attributed to joint laxity and/or impingement resulting in subluxation of the head, causing wear on the edge of the cup. Studies have been conducted into the effects of mild subluxation, however few in vitro tests have looked at severe subluxation. The aim of this study was to develop a more clinically relevant subluxation protocol.

Metal-on-Metal devices generate significantly lower volumetric wear than conventional total hip replacements. However, clinically some patients may suffer some form of laxity in their joints leading to subluxation of the joint, which in turn may cause edge loading of an implant thereby increasing the chances of failure due to higher than expected wear.

In this study, the effect of subluxation on MoM implant wear was investigated on a hip joint simulator.

Introduction

All hip replacements depend upon good orientation and positioning to ensure that implants function well in vivo. Mal-orientated devices can lead to poor patient gait, poor range of motion, impingement, edge loading and high wear, which in turn may result in the premature failure of the implants.

Introduction

Hip implant research has been carried out for decades using hip simulators to reflect situations in vivo. With regards to metal on metal (MoM) implant testing, it has been reported that there is no significant difference between the wear generated by various cobalt chromium (CoCr) microstructures. On the contrary, higher wear, metal ion levels and subsequent failures have been reported in heat treated (high carbon, low carbide) devices compared to as cast (high carbon, high carbide) devices in vivo. During testing, the bearing surfaces may be masked from the effect of microstructure on wear under fast and continuous cycles, while in vivo, the extensive range of kinetics and kinematics, stop/start motion, varying walking frequencies could break down the fluid film, resulting in a less favourable lubrication regime. The aims of this study were to develop a more physiologically relevant hip simulator test protocol, and investigate the effect of microstructure on wear.

Purpose: Vascular Endothelial Growth Factor (VEGF) plays an important role in promoting angiogenesis and osteogenesis during fracture repair. Our previous studies have shown that cell-based VEGF gene therapy accelerates bone healing of a rabbit tibia segmental bone defect in-vivo, and increases osteoblast proliferation and mineralization in-vitro. The aim of this project was to examine the effect of exogenous human VEGF (hVEGF) on the endogenous rat VEGF messenger RNA (mRNA) expression in a cell-based gene transfer model.

Method: The osteoblasts were obtained from the rat periosteum. The fibroblasts were obtained from the rat dermal tissue. The cells were then cultured to reach 60% confluence and transfected with hVEGF using Superfect. Four groups were:

osteoblast-hVEGF,

The cultured cells were harvested at 1, 3 and 7 days after the transfection. The total mRNA was extracted (TRIZOL); both hVEGF and rat VEGF mRNA were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantified by VisionWorksLS.

Results: The hVEGF mRNA was detected by RT-PCR from transfected osteoblasts after three days of gene transfection. The hVEGF mRNA expression in transfected fibroblasts increased exponentially at days 1, 3 and 7 after the transfection. We compared the endogenous rat VEGF mRNA expression level of the osteoblasts or fibroblasts that were transfected with hVEGF with the cells without the transfection. The hVEGF transfected osteoblasts had a greater rat VEGF mRNA expression than the non-transfected osteoblasts. Furthermore, when hVEGF was transfected to the rat fibroblasts, the endogenous mRNA expression level measured was also greater than that from the non-transfected fibroblasts. Rat VEGF mRNA expression increased in the first three days of the hVEGF transfection, but the expression level was reduced at Day 7.

Conclusion: These results suggest that cell-based hVEGF gene therapy enhances endogenous rat VEGF mRNA expression in both osteoblasts and fibroblasts.

Introduction: Although clinical results for the Metal-on-Metal (MoM) devices have been excellent, recently some concerns have been raised regarding the occurrence of periprosthetic soft tissue lesions (PSTL) in some patients with MoM devices. Clinical studies and retrieval analyses have shown that devices revised due to groin pain and PSTL generally have significantly higher wear that has been attributed to edge loading of the implants.

Aim: The retrieval study was to investigate the cause of edge-loading of MoM devices in vivo.

Materials and Methods: In this study 13 retrieved Birmingham Hip Resurfacing (BHR) devices were examined. All devices were supplied with radiographs showing the in vivo position of the implant. Linear wear was assessed using a Taylor-Hobson Talyrond 290 roundness machine. Multiple roundness profiles were obtained to locate the area of maximum wear on each component. Edge loaded devices were identified when the maximum linear wear occurred at the edge of the cup. Non-edge loaded pairs showed wear area within the articulating surface of the cup.

The in vivo abduction angle and version angle of the cup were determined by superimposing the BHR models onto the radiographs (ProEngineer Wildfire 4 with ISDX II extension software) using anatomical references and specific features of the BHR.

Results: Linear wear: Among the 13 devices investigated, 11 were edge loaded with the maximum linear wear occurred at the edge of the cup. The remaining 2 pairs were non-edge loaded. The average joint linear wear rate of the edge loaded devices was 49.9 μm per year, and that for the two non-edge loaded devices was 2.4 μm per year. Edge loaded pairs had far greater linear wear than non-edge loaded components.

Cup orientation: The abduction angles of the two non-edge loaded cups were 31° and 39°, and their version angles were 12 and 16° respectively. These angles were within recommended orientation for the BHR. In contrast, the adduction angles and/or version angles of all edge loaded devices were outside the recommended orientation. Their abduction angle varied from 40° to 66° and version angle from 5° to 46°.

The edge loaded devices with higher inclination angles and/or higher version angels generally had higher linear wear. There is strong correlation between the cup orientation and the linear wear of the implant.

Conclusion: Mal-orientated devices in this study showed clear signs of edge loading which in turn resulted in significant increase in wear compared to the well orientated/non-edge loaded devices.

Introduction: In vitro studies have shown that low clearance bearings have the potential to generate low wear. However, cementless acetabular cups are designed to be press fitted into the acetabulum, which could generate compressive stresses and non-uniform cup deformation during implantation. Deformation of the low clearance acetabular cups could also potentially lead to clamping or seizure of the joints and high frictional torque leading to implant failure. To obtain the benefit of low clearance and low wear, without compromising the tribological performance of the cup, a deflection compensation (DefCom) cup was designed. DefCom offers the benefits of low wear associated with low clearance components whilst reducing the risk of component seizure and high frictional torque due to component deformation.

Aim: The study was conducted in order to evaluate the tribological performance of a DefCom acetabular cup.

Materials and Methods: 50 mm diameter metal-on-metal DefCom hip resurfacing cups were used in this study. The components had an average clearance of 105±3 μm at the articulating sphere. Three of the cups were deformed plastically, along the ilial-ischeal column of the acetabulum. The degree of deformation was measured using the coordinate measuring machine, measuring the change in diameter of the cup in the direction of deformation. The cups were deformed on average by 65μm. The devices were tested in a ProSim hip wear Simulator for 5 million cycles. The lubricant was new born calf serum with 0.2% sodium azide diluted with de-ionised water to achieve protein concentration of 20 mg/ml. The flexion/extension was 30° and 15° with an internal/external rotation of ±10°. The force was Paul-type stance phase loading with a maximum load of 3 kN and a swing phase load of 0.3 kN, conducted at 1 Hz.

Results: The DefCom and deformed DefCom components showed a similar bi-phasic wear pattern to that of the BHR devices. Showing a period of ‘running in’ wear up to 1 Mc and then a reduced wear rate during the steady state phase from 1 Mc onwards. The DefCom devices produced a wear rate of 0.24 mm3/Mc, whilst the deformed DefCom joints produced a wear rate of 0.48 mm3/Mc for the running-in phase. Steady state wear was achieved for all joints after 1 Mc. The average steady state wear (1.0–5.0 Mc) rate for the DefCom joints was 0.12 mm3/Mc, with 0.14 mm3/Mc for the deformed joints joint. The wear rate for the non-deformed DefCom device is lower than that generated by the BHR, which were 0.72 mm3/Mc and 0.18 mm3/Mc for the running-in and steady state wear, respectively.

Conclusion: The study has shown that the DefCom acetabular cup has the potential to reduce the initial running-in wear by reducing the clearance at the contact area between the head and cup, whilst compensating for deformation that may occur during cup implantation.

Introduction: Based on the clinical success of large head metal-on-metal (MoM) bearings technologies in the resurfacing arena, a multi-bearing acetabular system, known as R3 system, was developed by Smith & Nephew. The novel R3 system utilizes porous coated Ti-6-4 shells in which liners of crosslinked UHMWPE, ceramic, or as-cast CoCr liners can be placed. The as-cast CoCr metallurgy and microstructure is identical to the clinically successful Birmingham Hip Replacement (BHR) resurfacing system. The design and manufacturing aspects such as diametrical clearance, surface roughness, and spherical form are all identical for the two systems.

Aim: to evaluate the tribological performance of R3 devices as compared to that of standard BHR devices.

Materials and Methods: Five pairs of 46 mm MoM R3 devices (Smith & Nephew) and three pairs of 48 mm BHR devices (Smith & Nephew) were tested in a ProSim hip wear Simulator. The lubricant was new born calf serum with 0.2% sodium azide diluted with de-ionized water to achieve protein concentration of 20 g/l. The flexion/extension was 30° and 15° and the internal/external rotation was +/− 10°. The force was Paul-type stance phase loading with a maximum load of 3 kN and a standard ISO swing phase load of 0.3 kN. The frequency was 1 Hz.

One R3 joint and one BHR device were friction tested in a ProSim hip friction simulator at 0, 3 and 5 million cycles of wear testing. The test was conducted in new born calf serum with added carboxy methyl cellulose (CMC) to generate viscosities of 1 to 100 cP. The loading cycle was set at maximum loads of 2 kN and minimum load of 0.1 kN. The flexion/extension was 30° and 15°, and the frequency was 1 Hz.

Results and Discussions:

Friction: The coefficient of friction (COF) of the R3 joint varied from 0.08 to 0.14 depending on the viscosity of the serum and cycles of wear simulation test. Under physiologically relevant lubricant conditions (1, 3 and 10 cP), the COF for the R3 device tested was comparable to that of the standard BHR device.

Conclusion: The test results presented in this study show that the tribological performances of the R3 and the BHR devices are comparable.

Introduction: The accepted method of assessing wear following a hip simulator test has been to use a precision balance. As the MoM devices produce significantly less weight loss than hard-on-soft bearings, the measurements of MoM devices are now almost at the detection limit of many balances. There is a need for a method that can be used in conjunction with gravimetric analysis that will provide an accurate assessment of ion concentration levels that will support the gravimetric measurements.

Aim: To develop a method to assess wear using metal ion analysis in order to support gravimetric measurements of metal on metal devices.

Materials and methods: Hip simulator test: Three pairs of 50 mm diameter as cast CoCr MoM devices were tested in a ProSim hip wear simulator (SimSol Stockport/UK) under physiologically relevant conditions. The lubricant was new born calf serum with 0.2 % sodium azide concentration diluted with de-ionised water for protein concentration of 20 g/l. Stop-start motion was implemented every 100 cycles. Lubricant changed every 125 k cycles. The frequency was 0.5 Hz. Wear was assessed gravimetrically at every 0.5 million cycles (Mc) interval.

Ion analysis: Serum was collected from test station and allowed to settle for 12 hours. An aliquot of 20 ml from lubricant was collected. Each sample was centrifuged at 2500 g-force for 10 minutes. A 10 ml aliquot was collected from each sample and was further centrifuged at 2500 g-force for 10 minutes. 1.5 ml aliquot was collected and stored at −20 °C. A high resolution inductively-coupled plasma mass spectrometry instrument (ELEMENT, ThermoFinnigan MAT, Bremen/Germany) was then used for the analysis of metal ions.

Results and Discussion: The average cumulative metal ion levels at 0.5, 1 and 1.5 Mc showed similar trends in wear to that of the average cumulative weight loss assessed gravimetrically. There were similar biphasic wear trends in both metal ion levels and gravimetric weight losses. Other studies have also shown similar correlation between volume loss and ion concentration levels. The percentage distribution of Co, Cr and Mo in the metal ion samples are in close agreement with nominal chemical composition of the material tested.

Conclusion: This study showed that metal ion measurements can help to confirm gravimetrically measured material loss.

Introduction: To develop a more physiologically relevant hip simulator test protocol and study the effect of microstructure on the wear performance of as-cast (AC) and double heat treated (DHT) devices under the new protocol.

Methods: Three pairs of AC and four pairs of DHT 50 mm CoCr metal-on-metal (MoM) devices were tested. The lubricant used was bovine serum. Stop-start motion was implemented between the two sets of kinetics and kinematics that alternated every 100 cycles throughout the test. Condition one: The flexion/extension was 30° and 15° respectively. The internal/external rotation was ±10°. The force was Paul type stance phase loading with a maximum load of 3 kN and a standard ISO swing phase load of 0.3 kN. Condition two: The flexion/extension was ±22°. The internal/external rotation was ±8°. The force was a maximum stance phase load of 2.2 kN and a swing phase load of 0.24 kN at 0.5 Hz frequency. Wear was assessed gravimetrically.

Result: The masking effect of 1 Hz speed and uninter-rupted motion, in providing exaggerated lubrication regime, was exposed under more physiologically relevant test conditions. The AC devices have significantly reduced wear when compared to the DHT devices. It can also be seen that from 0.5 to 2 Mc the divergence in wear has increased.

Conclusion: A more physiologically relevant hip simulator test protocol was successfully developed and implemented, in showing the effect of microstructure on wear as seen in vivo, where high wear of DHT devices has been observed. 295

Hip simulators have been used for ten years to determine the tribological performance of large-head metal-on-metal devices using traditional test conditions. However, the hip simulator protocols were originally developed to test metal-on-polyethylene devices. We have used patient activity data to develop a more physiologically relevant test protocol for metal-on-metal devices. This includes stop/start motion, a more appropriate walking frequency, and alternating kinetic and kinematic profiles.

There has been considerable discussion about the effect of heat treatments on the wear of metal-on-metal cobalt chromium molybdenum (CoCrMo) devices. Clinical studies have shown a higher rate of wear, levels of metal ions and rates of failure for the heat-treated metal compared to the as-cast metal CoCrMo devices. However, hip simulator studies in vitro under traditional testing conditions have thus far not been able to demonstrate a difference between the wear performance of these implants.

Using a physiologically relevant test protocol, we have shown that heat treatment of metal-on-metal CoCrMo devices adversely affects their wear performance and generates significantly higher wear rates and levels of metal ions than in as-cast metal implants.

Aim of the study: To evaluate the use of a gelfoam sponge as a scaffold material in delivering osteoblast cells transfected with the VEGF gene for fracture repair.

Methods: In vitro: Osteoblasts were cultured from periosteum of rabbit bone and labeled with the visible CMTMR. Commercially available gelfoam with 12 pieces (each 3 × 3 × 3 mm3) was impregnated and cultured with the labelled cells (1×106) in a 12 wells plate for 1, 3 and 7 days. We embedded the gelfoam with labeled cells in an OCT compound enface, and the sections were then examined under a fluorescent microscope. In vivo: Osteoblasts were transfected with VEGF by use of SuperFect (Qiagen Inc) and cultured for 24 hours. The gelfoam pieces were impregnated with the transfected cells (5×106) saline solution for 30 minutes and placed into a segmental bone defect created in the rabbit tibia for 7 (n=3) and 14 (n=3) days. The specimens including the new bone were cut through each site of the segmental defect and embedded in paraffin. The sections were dewaxed and immunostained with mouse anti-human VEGF.

Results: In vitro: CMTMR-labeled cells survived and were detected within gelfoam at different time intervals (days 1, 3 and 7). In vivo: Immunostained VEGF proteins were visualized in the tissues surrounding the residual gel-foam at the fracture site at days 7 and 14 post surgery.

Conclusion: Our results indicate that the labeled/transfected cells are capable of growth in a gelfoam sponge both in vitro and in vivo.

Introduction: Cementless cup designs in metal-on-metal (MoM) hip resurfacing devices generally depend on a good primary press-fit fixation which stabilises the components in the early post-operative period. Pressfitting the cup into the acetabulum generates non-uniform compressive stresses on the cup and consequently causes non-uniform cup deformation. That in turn may result in equatorial contact, high frictional torque and femoral head seizure. It has been reported that high frictional torque has the potential to generate micromotion between the implant and its surrounding bone and as a result adversely affect the longevity of the implant. The aim of this study was to investigate the effects of cup deformation on friction between the articulating surfaces in MoM bearings with various clearances.

Materials and methods: Six Birmingham Hip Resurfacing (BHR) devices with various clearances (80 to 306 μm) were tested in a hip friction simulator to determine the friction between the bearing surfaces. The components were tested in clotted blood which is the primary lubricant during the early post-operative period. The joints were friction tested initially in their pristine conditions and subsequently the cups were deflected by 25– 35 μm using two points pinching action before further friction tests were carried out.

Results and Discussions: It has been reported that reduced clearance results in reduced friction. However, none of the previous studies have taken cup deflection into consideration nor have they used physiologically relevant lubricant. The results presented in this study show that for the reduced clearance components, friction was significantly increased when the cups were deflected by only 30 μm. However, for the components with higher clearance the friction did not change before and after deflection. It is postulated that the larger clearances can accommodate for the amount of distortion introduced to the cups in this study.

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to suppress bone repair and remodeling in vivo. Our previous studies showed that NSAIDs inhibited osteoblast proliferation and induced cell death in fetal rat osteoblast cultures. However, the NSAIDs effects on the functions of human osteoblasts remain unclear. Newly developed selective cyclo-oxygenase 2 (COX-2) inhibitors, celecoxib and refecoxib, have been reported to have lower risk of gastrointestinal complications than traditional nonsteroidal anti-inflammatory drugs. A recent report showed that refecoxib decreased bone ingrowth in an animal study. However, the effects of COX-2 selective inhibitors on human osteoblasts have rarely been investigated. In this study, the effects of steroid, non-selective, and selective COX-2 inhibitors on proliferation, cell cycle kinetics, and cytotoxicity in cultured human osteoblasts were examined.

Materials and Methods: Indomethacin,ketorolac,piroxicam, and diclofenac (10⁻⁵ and 10⁻⁴M); dexamethasone (10⁻⁷ and 10⁻⁶M); Celecoxib and DFU, an analogue of rofecoxib, (10⁻⁷–10⁻⁴M) were tested for 24 or 48 hr in human osteoblast cultures.

Results: In this study, we found that a 24 hour treatment of COX-2 selective inhibitors, celecoxib and DFU, significantly inhibited proliferation, arrested cell cycle, and had cytotoxicity in cultured human osteoblasts. However, the inhibitory effect on proliferation could be reversed if these agents were withdrawn for 24 hours. Indomethacin, ketorolac, diclofenac, and piroxicam also significantly inhibited proliferation and arrested cell cycle at the G₀/G₁ phase, but had no cytotoxic effects on human osteoblasts.

Discussion: These results suggest that the COX-2 selective and non-selective NSAIDs may affect osteoblastic functions through different mechanisms.

The total plasma alkaline phosphatase level has long been recognised as an indicator of osteoblastic activity, but lack of specificity makes it an insensitive index of the progress of disease and the response to treatment. Selective precipitation by wheatgerm lectin allows measurement of the plasma bone-specific alkaline phosphatase. We measured the plasma levels of this isoenzyme in 170 normal Chinese adolescents and adults, in 49 adults with fractures of a long bone, in 15 patients with osteosarcoma and in 38 patients with osteolytic metastases. The enzyme activity was also determined in 39 patients with liver disease. Of the patients with fractures, 94% had increased plasma activity during the healing process. The level was also increased in those with osteosarcoma but not in those with osteolytic bone metastases. There was no significant increase in activity in the patients with liver disease. We conclude that the plasma bone-specific alkaline phosphatase activity is a sensitive and reliable measure of osteoblastic activity.