For patients who took joint replacement, one of the complications, aseptic joint loosening, could cause a high risk of revision surgery. Studies have shown that MSCs have the ability of homing and differentiating, and also have highly effective immune regulation and anti-inflammatory effects. However, few studies had focused on the stem cells in preventing the occurrence and development of aseptic loosening. In this research, we aimed to clarify whether human umbilical cord mesenchymal stem cells could inhibited the aseptic joint loosening caused by wear particles. A Cranial
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
Failure of osseointegration and periprosthetic joint infection (PJI) are the two main reasons of implant failure after total joint replacement (TJR). Nanofiber (NF) implant surface coating represents an alternative local drug eluting device that improves osseointegration and decreases the risk of PJI. The purpose of this study was to investigate the therapeutic efficacies of erythromycin (EM)-loaded coaxial PLGA/PCL-PVA NF coating in a rat S. aureus-infected tibia model. NF coatings with 100mg and 1000mg EM were prepared. NF without EM was included as positive control. 56 Sprague Dawley rats were divided into 4 groups. A titanium pin (1.0-mm x 8 mm) was placed into the tibia through the intercondylar notch. S. aureus (SA) was introduced by both direct injection of 10 μl broth (1 × 10. 4. CFU) into the medullary cavity and single dip of Ti pins into a similar solution prior to insertion. Rats were sacrificed at 8 and 16 weeks after surgery. The outcome measurements include μCT based quantitative
Introduction and Objective. Total joint replacement is indicated for osteoarthritis where conservative treatment has failed, and in the UK the number of patients requiring hip and knee replacements is set to increase with an ageing population. Survival of total hip replacements is around 85% at 20 years with the most common reason for revision being aseptic loosening of the implant secondary to
Wear debris from implant interfaces is the major factor leading to periprosthetic osteolysis. Fibroblast-like synoviocytes (FLSs) populate the intimal lining of the synovium and are in direct contact with wear debris. This study aimed to elucidate the effect of Ti particles as wear debris on human FLSs and the mechanism by which they might participate in the bone remodeling process during periprosthetic osteolysis. FLSs were isolated from synovial tissue from patients, and the condition medium (CM) was collected after treating FLSs with sterilized Ti particles. The effect of CM was analyzed for the induction of osteoclastogenesis or any effect on osteogenesis and signaling pathways. The results demonstrated that Ti particles could induce activation of the NFκB signaling pathway and induction of COX-2 and inflammatory cytokines in FLSs. The amount of RANL in the conditioned medium collected from Ti particle-stimulated FLSs (Ti CM) showed the ability to stimulate osteoclast formation. The Ti CM also suppressed the osteogenic initial and terminal differentiation markers for osteoprogenitors, such as alkaline phosphate activity, matrix mineralization, collagen synthesis, and expression levels of Osterix, Runx2, collagen 1α, and bone sialoprotein. Inhibition of the WNT and BMP signaling pathways was observed in osteoprogenitors after the treatment with the Ti CM. In the presence of the Ti CM, exogenous stimulation by WNT and BMP signaling pathways failed to stimulate osteogenic activity in osteoprogenitors. Induced expression of sclerostin (SOST: an antagonist of WNT and BMP signaling) in Ti particletreated FLSs and secretion of SOST in the Ti CM were detected. Neutralization of SOST in the Ti CM partially restored the suppressed WNT and BMP signaling activity as well as the osteogenic activity in osteoprogenitors. Our results reveal that wear debris-stimulated FLSs might affect bone loss by not only stimulating osteoclastogenesis but also suppressing the bone-forming ability of osteoprogenitors. In the clinical setting, targeting FLSs for the secretion of antagonists like SOST might be a novel therapeutic approach for preventing bone loss during inflammatory
The most common reason for revision surgery of total hip replacements is aseptic loosening of implants secondary to
Introduction and Objective. Total joint replacement (TJR) is indicated for patients with end-stage osteoarthritis (OA) where conservative treatment has failed. Approximately 1.3 million primary hip replacement surgeries have been recorded in the United Kingdom since 2003 and this number is set to rise due to an increase in obesity as well as an ageing population. Total hip replacement (THR) has a survival rate of 85% at 20 years; the most common reason for failure is aseptic loosening which often occurs secondary to
Breast cancer is the most frequent malignancy in women with an estimation of 2.1 million new diagnoses in 2018. Even though primary tumours are usually efficiently removed by surgery, 20–40% of patients will develop metastases in distant organs. Bone is one of the most frequent site of metastases from advanced breast cancer, accounting from 55 to 58% of all metastases. Currently, none of the therapeutic strategies used to manage breast cancer bone metastasis are really curative. Tailoring a suitable model to study and evaluate the disease pathophysiology and novel advanced therapies is one of the major challenges that will predict more effectively and efficiently the clinical response. Preclinical traditional models have been largely used as they can provide standardization and simplicity, moreover, further advancements have been made with 3D cultures, by spheroids and artificial matrices, patient derived xenografts and microfluidics. Despite these models recapitulate numerous aspects of tumour complexity, they do not completely mimic the clinical native microenvironment. Thus, to fulfil this need, in our study we developed a new, advanced and alternative model of human breast cancer bone metastasis as potential biologic assay for cancer research. The study involved breast cancer bone metastasis samples obtained from three female patients undergoing wide spinal decompression and stabilization through a posterior approach. Samples were cultured in a TubeSpin Bioreactor on a rolling apparatus under hypoxic conditions at time 0 and for up to 40 days and evaluated for viability by the Alamar Blue test, gene expression profile, histology and immunohistochemistry. Results showed the maintenance and preservation, at time 0 and after 40 days of culture, of the tissue viability, biological activity, as well as molecular markers, i.e. several key genes involved in the complex interactions between the tumour cells and bone able to drive cancer progression, cancer aggressiveness and metastasis to bone. A good tis sue morphological and microarchitectural preservation with the presence of lacunar
Introduction. Durable bone fixation of uncemented porous-coated acetabular cups can be observed at a long-term, however, polyethylene (PE) wear and
Introduction and Objective. Difficult primary total knee arthroplasty (TKA) and revision TKA are high demanding procedures. Joint exposure is the first issue to face off, in order to achieve a good result. Aim of this study is to evaluate the clinical and radiological outcomes of a series of patients, who underwent TKA and revision TKA, where tibial tubercle osteotomy (TTO) was performed. Materials and Methods. We retrospectively reviewed a cohort of 79 consecutives TKAs where TTO was performed, from our Institution registry. Patients were assessed clinically and radiographically at their last follow-up (mean, 7.4 ± 3.7 years). Clinical evaluation included the Knee Society Score (KSS), the pain visual analogue scale (VAS), and range of motion. Radiological assessment included the evaluation of radiolucent lines,
Abstract. Background/Objectives. The incidence of reverse total shoulder replacement (rTSR) implantation is increasing globally, but apprehension exists regarding complications and associated challenges. We retrospectively analysed the senior author's series of rTSR from a tertiary centre using the VAIOS shoulder system, a modular 4th generation implant. We hypothesised that the revision rTSR cohort would have less favourable outcomes and more complications. Methods. 114 patients underwent rTSR with the VAIOS system, over 7 years. The primary outcome was implant survival. Secondary outcomes were Oxford shoulder scores (OSS), radiographic analysis (scapular notching, tuberosity
Abstract. Objective. The aim of our systematic review was to report the latest evidence on the effects of CoCr particles on local soft tissue with a focus on its clinical relevance. Methods. PubMed, Embase, and Cochrane Library databases were screened to perform an extensive review. Inclusion criteria were studies of any level of evidence published in peer-reviewed journals reporting clinical and preclinical results written in English. Relative data were extracted and critically analyzed. PRISMA guidelines were applied, and the risk of bias was assessed, as was the methodological quality of the included studies. Results. 30 studies were included after applying the inclusion and exclusion criteria. Of these, 24 were preclinical studies (18 in vitro human studies, 6 animal modal studies, including 3 in vitro and 3 in vivo), 5 were clinical studies and 1 was previous review on similar topic. The presence of metal ions causes cell damage by reducing cell viability, inducing DNA damage, and triggering the secretion of cytokines. Mechanisms of apoptosis, autophagy and necrosis are responsible for the inflammatory reaction observed in ALTR. Conclusion. The available literature on the effects of CoCr particles released from MoM implants shows that metal debris can cause damage to skeletal muscle, the capsule, and provoke
Total Hip Arthroplasty (THA) is a well-established, cost-effective treatment for improving function and alleviating pain in patients who have disabling hip disease with excellent long-term results. Based on the excellent results, there is an ongoing trend for THA to be performed in younger and more active patients, having higher physical demands on their new total joints. Polyethylene (PE) wear and its biological consequences are one of the main causes of implant failure in THA. Macrophages phagocytise PE wear particles and this will result in
This longitudinal microCT study revealed the osteolytic response to a Staphylococcus epidermidis-infected implant in vivoand also demonstrates how antibiotics and/or a low bone mass state influence the morphological changes in bone and the course of the infection. Colonisation of orthopaedic implants with Staphylococcus aureusor S. epidermidisis a major clinical concern, since infection-induced
Abstract. Objective. In this phase 2 clinical trial (EudraCT 2011-000541-20) we examined the effect of denosumab versus placebo on osteolytic lesion activity in patients undergoing revision surgery after THA. Methods. Men and women ≥ 30 years old scheduled for revision surgery for symptomatic, radiologically-confirmed
Abstract. Objectives. Implant loosening remains a common cause of total ankle replacement (TAR) revision, and has been associated with wear-mediated
Summary Statement. Vitamin E-UHMWPE particles have a reduced
INTRODUCTION. Staphylococci species account for ∼80 % of osteomyelitis cases. While the most severe infections are caused by Staphylococcus aureus (S. aureus), the clinical significance of coagulase negative Staphylococcus epidermidis (S. epidermidis) infections remain controversial. In general, S. epidermidis was known to be a protective commensal bacterium. However, recent studies have shown that intra-operative low-grade S. epidermidis contamination prevents bone healing. Thus, the purpose of this study is to compare the pathogenic features of S. aureus and S. epidermidis in an established murine model of implant-associated osteomyelitis. METHODS. All animal experiments were performed on IACUC approved protocols. USA300LAC (MRSA) and RP62A(S. epidermidis) were used as prototypic bacterial strains. After sterilization, stainless steel pins were implanted into the tibiae of BALB/c mice (n=5 each) with or without Staphylococci. Mice were euthanized on day 14, and the implants were removed for scanning electron microscopy (SEM). Tibiae were fixed for mCT prior to decalcification for histology. RESULTS. The histology of S. aureus infected tibiae demonstrated massive
Aseptic loosening is a major cause of revision surgeries and occurs when
Summary. Osteoporosis reduces particle-induced