Abstract. Background. Post operative radiographs following total joint arthroplasty are requested as part of routine follow up in many institutions. These studies have a significant cost to the local departments, in terms of financial and clinic resources, however, previous research has suggested they may not alter the course of the patients treatment. The purpose of this study was to assess the significance of elective post operative radiographs on changes in management of patients who underwent total joint arthroplasty. Method. All patients who underwent total knee arthroplasty and total hip arthroplasty at a District General Hospital from 2019 to 2020 were included. Data was collected retrospectively from medical records and radiograph requests. Alterations to clinical management based on radiographic findings were reviewed in clinic letters. Results. A total of 227 Total joint arthroplasty were retrieved. With 111(49%) total hip arthroplasty and 116 (51%) total knee arthroplasty. 54 were excluded due to having no clinical follow up and 173 met inclusion criteria. 56 (32%) had their post operative elective radiograph, while 93 (53.8%) patients had none. There were no abnormalities detected from the elective radiographs and none of the patients returned to the theatre. 24 patients (13%) presented with symptoms and had non-elective radiographs, 16 (67%) did not have any interventions and 8 (4.6%) required intervention and were taken to theatre. Discussion: Not performing these radiographs saves time, cost, and prevents unnecessary radiation exposure. In our institution, a 2-view joint radiograph costs £29 and takes roughly 15 minutes. This does not include indirect costs of additional clinic time and patient waiting time. In the larger context, the cost associated with elective radiographs is significant and our data suggests that routine post-operative radiographs are not beneficial as part of standard post-operative protocol for asymptomatic patients. However, performing imaging remains beneficial for patients who re-present with symptoms. Conclusion. Routine elective post-operative joint radiographs did not detect any true abnormalities. Information from elective radiographs has no clinical significance and did not change management. Therefore, this study recommends that there is no rationale requesting elective post-operative joint radiographs. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Introduction. Infections in total joint arthroplasty (TJA) are a burden to the healthcare system. An infection in total joint arthroplasty costs nearly $60,000–80,000 to the system. 3 major tenets to decrease surgical site infections, focus on patient preoperative optimization, intraoperative techniques, and postoperative care. Intraoperative vancomycin powder been successful in lowering infection rates in other areas of orthopaedics. The purpose of our study was to investigate whether topical intraoperative vancomycin powder had any effect on surgical site infection, complication rate, or reoperation rate. Our hypothesis was vancomycin powder may decrease the rate of surgical site infections without any effect on wound complications. Materials & Methods. 208 consecutive patients undergoing either total hip or total knee arthroplasty (THA or TKA) were given intraoperative vancomycin powder or none. 64 patients received vancomycin poweder compared to 164 patients who did not. All preoperative, intraoperative and postoperative management was similar. Preoperative data including age, sex, BMI, diabetes status and comorbidities were recorded. Surgical techniques included medial parapatellar or subvastus for TKA, posterolateral for THA. 90-day culture positive infection and reoperation rates were recorded. Results. Preoperative variables between the two groups were similar. Average age, ASA, BMI, diabetes status and other preoperative patient variables were not significantly different (p=0.31, 0.19, 0.65, 0.31). 5/64 patients (7.8%) in the vancomycin group underwent reoperation, compared with 13/164 (9.0%) in the no vancomycin group. There was no difference in the rate of reoperations (p=0.777). Of these patients, 3/64 (4.69%) patients in the vancomycin group had a positive infection compared with 8/164 (5.55%) in the no vancomycin group. There was no significant differences between the two infection rates (p=0.807). Discussion. Surprisingly, vancomycin powder did not have any effect on reoperation nor infection rates in our study group. Although other studies may have shown a decrease in infection, ours failed to do so. Due to low study numbers, we could not differentiate deep versus superficial surgical site infections. Based on our study, we are unable to recommend the use of intraoperative vancomycin powder for total joint arthroplasty

Excessive opioid prescriptions after total joint arthroplasty (TJA) increase risks for adverse opioid related events, chronic opioid use, and increase the availability of opioids for unlawful diversion. Thus, decreasing postoperative prescriptions may improve quality after TJA. Concerns exist that a decrease in opioids prescribed may increase complications such as readmissions, emergency department (ED) visits or worsened patient reported outcomes (PROs). The purpose of this quality improvement study was to explore whether a reduction in opioids prescribed after TJA resulted in increased complications. Methods: Data originated from a statewide arthroplasty database (MARCQI). The database collects over 96% of all TJA performed in the state of Michigan, USA. Data was prospectively abstracted and included OMEs prescribed at discharge, readmissions, ED visits within 30 days and PROs. Data was collected one year before and after the creation of an opioid prescribing protocol that had decreased prescriptions by approximately 50% in opioid naive and tolerant patients. Trends were monitored using Shewhart control charts. 84,998 TJA over two-years were included. All groups showed a reduction in opioids prescribed. Importantly, no increased complications occurred concomitant to this reduction. No increases in ED visits or readmissions, and no decreases in KOOSJR/HOOSJR/PROMIS10 scores were noted in any of the groups. Using large data sets and registries can drive performance and improve quality. The MARCQI Postoperative opioid prescription recommendations and performance measures decreased total oral morphine equivalents prescribed over a large and diverse population by approximately 50% without decreasing PROs or increasing ED visits or hospital readmissions. A reduction in opioids prescribed after TJA can be accomplished safely and without an increase in complications across a large population

Background. Inflammation and chemokines play a pivotal role in aseptic loosening (AL) and prosthetic joint infection (PJI) of total joint arthroplasty (TJA). Recently, the Duffy antigen receptor for chemokines (DARC) on erythrocytes was identified as a potent chemokine receptor able to bind and carry without deactivating a wide range of CXC and CC chemokines from circulation to tissues. The role of DARC and its functional polymorphism (SNP) influencing the number of the DARC molecules on the erythrocytes in AL/PJI has not been studied yet. Methods. We genotyped functional polymorphism in the DARC gene (rs12075) using MassArray technology (Agena Bioscience) in 354 patients with TJA (hip and knee arthroplasties). Patients were further subdivided into those with a complication (AL, n = 110; PJI, n = 126) and a control group without complications for at least 10 years (n = 118). Statistics was performed by Plink 1.07 and relative entropy. Results. Among our TJA patients, the rs12075 *G allele was more frequent in patients with a failure (46.6%) compared to those without complications (36.0%, P = 0.007, OR = 1.55, 95%CI = 1.13–2.14). The rs12075 *G allele was overrepresented mainly in patients with AL (49.5%, P = 0.004, OR = 1.74, 95%CI = 1.20–2.54), a trend was observed in PJI (44.0%, P = 0.071, OR =1.40, 95%CI = 0.97–2.01). This SNP is located in a coding region in the DARC gene, and the *G allele is associated with more DARC molecules on erythrocytes, thus able to bind and transport more CCL2, CCL5, CCL18 involved in the pathogenesis of AL/PJI from circulation to the periprosthetic tissue. Conclusions. Our data nominate erythrocyte DARC as a novel molecule in pathogenesis of aseptic loosening of TJA. The hypothesis that DARC may serve as a chemokine reservoir and shuttle chemokines from circulation to the joint surroundings should be investigated in future studies. Level of evidence IV. Evidence from well-designed case-control and cohort studies. The study was approved by the Ethical Committee of Palacky University and Faculty

The most common reasons for total joint arthroplasty (TJA) failure are aseptic loosening (AL) and prosthetic joint infection (PJI). There is a big clinical challenge to identify the patients with high risk of AL/PJI before the TJA surgery. Although there is evidence that genetic factors contribute to the individual susceptibility to AL/PJI, a predictive model for identification of patients with a high genetic risk of TJA failure has not been developed yet. We aimed to develop a risk evaluation tool utilising the AL/PJI-associated polymorphisms for identification of patients with high genetic risk of TJA failure based on inflammation-gene polymorphism panel. Based on allele and genotype frequencies of twenty-five single nucleotide polymorphisms (SNPs) in TNF, IL2, IL6, IL10, IL1b, IL-1Ra, MBL2, MMP1, FTO genes and those influencing the serum levels of biomarkers of TJA outcomes (IL6, CCL2/MCP-1, CRP, ESR) in peripheral blood obtained from patients with TJA (AL, n=110; PJI, n=93; no complications, n=123), we calculated a hazard ratio and a relative entropy of alleles and genotypes associated with AL and PJI and their combinations in patient subgroups. We conducted a risk evaluation tool based on the presence of risk alleles and genotypes in TNF (rs361525, rs1800629), DARC (rs12075), MBL2 (rs11003125) and FTO (rs9939609, rs9930506) genes associated with implant failure (AL/PJI). Of these, FTO gene variations (rs9939609, rs9930506) were associated mainly with PJI (P=0.001, OR=2.04, 95%CI=1.132–2.603; P=0.011, OR=1.72, 95%CI=1.338–3.096) and DARC (rs12075) with AL (P=0.005, OR=1.79, 95%CI=1.193–2.696). This tool calculates a hazard ratio of a combination of SNPs associated with AL and PJI for identification of patients with high and low risk of AL/PJI TJA failure. We proposed a risk evaluation tool for stratification of patients before the TJA surgery based on the genetic risk of AL/PJI development. The effect size for each genotype combination described in the study is small. Further multiparametric data analysis and studies on an extended patient cohort and other non-genetic and genetic parameters are ongoing. Grant support: AZV MZ CR VES16-131852A, VES15-27726A, IGA LF UP_2016_011

Background

Smoking has been associated with poor tissue oxygenation and vascularisation, predisposing smokers to a higher risk for postsurgical infections. The aim of this study was to estimate and compare the incidence of prosthetic joint infection (PJI) following primary total joint arthroplasty (TJA) according to smoking status.

Background

To investigate whether the interaction between pre-operative widespread hyperalgesia and radiographic osteoarthritis (OA) was associated with pain severity before and after total hip replacement (THR) and total knee replacement (TKR).

We aimed to assess whether the immunological abnormalities which have been observed in patients with loose total hip replacements (THRs) are present in patients with a well-fixed prosthesis.

We examined blood samples from 39 healthy donors, 22 patients before THR and 41 with well-fixed THRs of different types (15 metal-on-metal, 13 metal-on-polyethylene, 13 ceramic-on-ceramic). Before THR, the patients showed a decrease in leukocytes and myeloid cells in comparison with healthy donors, and a prevalence of type-1 T lymphocytes, which was confirmed by the increase in ratio of interferon-γ to interleukin 4. Moreover, patients with metal-on-metal or metal-on-polyethylene implants showed a significant decrease in the number of T lymphocytes and a significant increase in the serum level of chromium and cobalt, although no significant correlation was observed with the immunological changes. In the ceramic-on-ceramic group, leukocytes and lymphocyte subsets were not significantly changed, but a significant increase in type-2 cytokines restored the ratio of interferon-γ to interleukin 4 to normal values.

We conclude that abnormalities of the cell-mediated immune response may be present in patients with a well-fixed THR, and that the immunological changes are more evident in those who have at least one metal component in the articular coupling.

Objectives

Infection of implants is a major problem in elective and trauma surgery. Heating is an effective way to reduce the bacterial load in food preparation, and studies on hyperthermia treatment for cancer have shown that it is possible to heat metal objects with pulsed electromagnetic fields selectively (PEMF), also known as induction heating. We therefore set out to answer the following research question: is non-contact induction heating of metallic implants effective in reducing bacterial load in vitro?

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

Prosthetic Joint Infection (PJI) is a devastating complication that can occur after total joint replacement surgery. With increasing antimicrobial resistance, there is a need for non-antibiotic approaches to treat and prevent PJI. Doping calcium phosphates with antimicrobial ions shows promise for these purposes. This systematic review aims to search and summarise the evidence-base for the potential of calcium phosphates doped with different antimicrobial ions. A systematic review was conducted on PubMed, Embase, Web-Of-Science, Cochrane Library and Emcare of in vitro and animal studies on the antimicrobial activity of (co)substituted calcium phosphates according to PRIMSA guidelines.. The research protocol, listing search terms and in/exclusion criteria, was registered a priori at . https://doi.org/10.7910/DVN/HEP18U. Data was extracted regarding ions, micro-organisms and antimicrobial activity. The search retrieved 1017 hits of which 148 papers were included. The substitution of 33 different ions was reported. Silver (n= 46), zinc (n=39), copper (n=18) and magnesium (n=14) were the most commonly doped ions. 36 different micro-organisms were studied of which E. coli (n=109), S. aureus (n=99), and C. albicans (n=22) were the most common. 6 different outcomes were reported, most commonly the K-ratio (n=53), the log CFU (n=41) and the bacterial inhibition zone (n=39). A validated outcome for the evaluation of biofilm prevention was lacking. There was considerable heterogeneity in studied ions, micro-organisms and reported outcomes. A lack of clearly defined reporting guidelines in the field of antimicrobial materials has led to the use of clinically irrelevant micro-organisms and a general lack of consistency of the methods used and the reported results. Currently, there is no universally accepted measure for the effectiveness required from biomaterials for treatment and prevention of PJI

Extensor mechanism and abductor reconstructions in total joint arthroplasty are problematic. Growing tendon into a metallic implant would have great reconstructive advantages. With the introduction of porous metal implants, it was hoped that tendons could be directly attached to implants. However, the effects of the porous metal structure on tissue growth and pore penetration is unknown. In this rat model, we investigated the effect of pore size on tendon repair fixation using printed titanium implants with differing pore sizes. There were four groups of six Sprague Dawley rats (n = 28) plus control (n=4). Implants had pore sizes of 400µm (n=8), 700µm (n=8), and 1000µm (n=8). An Achilles tendon defect was created, and the implant positioned and sutured between the cut ends. Harvest occurred at 12-weeks. Half the specimens underwent tensile load to failure testing, the other half fixed and processed for hard tissue analysis. Average load to failure was 72.6N for controls (SD 10.04), 29.95N for 400µm (SD 17.95), 55.08N for 700µm (SD 13.47), and 63.08N for 1000µm (SD 1.87). The load to failure was generally better in the larger pore sizes. Histological evaluation showed that there was fibrous tendon tissue within and around the implant material, with collagen fibers organized in bundles. This increases as the pore diameter increases. Printing titanium implants allows for precise determination of pore size and structure. Our results showed that tendon repair utilizing implants with 700µm and 1000µm pores exhibited similar load to failure as controls. Using a defined pore structure at the attachment points of tendons to implants may allow predictable tendon to implant reconstruction at the time of revision arthroplasty

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 osteolysis evaluation and hard tissue histology. Results: EM-NF coating (EM100 and EM1000) reduced osteolysis at 8 and 16 weeks, compared to EM0 and negative control. The effective infection control by EM-NFs was further confirmed by hard tissue section analysis. The Bone implant contact (BIC) and bone area fraction Occupancy (BAFO) within 200 µm of the surface of the pins were used to evaluate the osseointegration and new bone formation around the implants. At 16 weeks, the bone implant contact (BIC) of EM 100 (35.08%) was higher than that of negative control (3.43%) and EM0 (0%). The bone area fraction occupancy within 200 µm (BAFO) of EM100 (0.63 mm2) was higher than that of negative control (0.390 mm2) and EM0 (0.0 mm. 2. ). The BAFO of EM100 was also higher than that of EM1000 (0.3mm. 2. ). There was much less osteolysis observed with EM100 and EM1000 NF coatings at 16 weeks, as compared to EM0 positive control, p=0.08 and p=0.1, respectively. Osseointegration and periprosthetic bone formation was enhanced by EM-NFs, especially EM100. Data from this pilot study is promising for improving implant surface fabrication strategies

Total joint replacement is a successful clinical intervention. However, aseptic loosening due to wear related particulate debris is still one of the most frequent reasons for late revision of total joint replacement. This lecture gives an overview about the application of methods to study wear and friction in total joint replacements (e.g. hip, knee, shoulder). This involves complex joint simulation conditions as well as analytical assessments. Regarding joint simulation the focus will be on ligament stabilized joints. New approaches will be shown and discussed. Furthermore, analytical methods to study the release of wear products in term of solid particles and soluble complexes like metal ions will be presented

Abstract. Objectives. Current use of hard biomaterials such as cobalt-chrome alloys or ceramics to articulate against the relatively soft, compliant native cartilage surface reduces the joint contact area by up to two thirds. This gives rise to high and abnormal loading conditions which promotes degradation and erosion of the mating cartilage leading to pain, stiffness, and loss of function. Biomimetic soft lubrication strategies have been developed by grafting hydrophilic polymers onto substrates to form a gel-type surface. Surface grafted gels mimic the natural mechanisms of friction dissipation in synovial joints, showing a promising potential for use in hemiarthroplasty. This project aims to develop implant surfaces with properties tailored to match articular cartilage to retain and promote natural joint function ahead of total joint replacement. Methods. Four different types of monomers were grafted in a one-step photopolymerisation procedure onto polished PEEK substrates. The functionalised surfaces were investigated using surface wettability, FTIR, and simplified 2D-tribometry tests against glass and animal cartilage specimens to assess their lubricity and mechanical properties for hemiarthroplasty articulations. Results. Polymer functionalised surfaces under different grafting conditions were assessed for their wettability, graft density and quality. A reduction in water contact angle from 90° to < 20° was seen for functionalised highly hydrophilic PEEK surfaces. Similarly a reduction in the coefficient of friction (and subsequently shear stresses acting on cartilage) of 95% to ∼ 10. −2. was seen for functionalised PEEK surfaces slid against glass and cartilage in PBS. Conclusions. Development of this technology has the potential to vastly improve the performance of hemiarthroplasty. Providing earlier and targeted interventions for degenerative joint disease whilst preserving the function of the remaining healthy cartilage. Future work will concern using these promising hydrated functionalised surface architectures as focal cartilage deflects plugs along with long-term performance and suitability for implantation assessments using joint simulator testing

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 osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can also cause pseudotumour formation. As revision surgery is associated with higher morbidity, mortality, infection rates, venous thromboembolism, resource demand and poorer subsequent function it is important to understand the mechanisms underlying the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4), an innate immune receptor, has been demonstrated to mediate deleterious immune responses by the Tyson-Capper research group, including inflammatory cytokine interleukin-8 (IL-8) secretion. Statin use in epidemiological studies has been associated with reduced overall risk of revision surgery after hip replacement. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses which can lead to osteolysis and pseudotumour formation. As literature from cardiological investigations demonstrate that statins can reduce the expression and responsiveness of TLR4, this could be an exciting mechanism to exploit to reduce the host immune response to orthopaedic wear debris, thereby improving implant survival by reducing immune mediated osteolysis. This ongoing study investigates simvastatin's effect on cobalt ion-mediated changes in gene and protein expression of interleukin-8 and soluble-ICAM-1 (sICAM-1) which is an angiogenic factor implicated in pseudotumour formation. Materials and Methods. TLR4-expressing human monocyte/macrophage THP-1 cells were pre-incubated with 50μM simvastatin for 2-hours or a vehicle control, before being exposed to exposed to 0.75mM cobalt chloride, in addition to a further 24-hour co-incubation with 50μM simvastatin or vehicle control. IL-8 protein and sICAM-1 secretion was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression changes were quantified by TaqMan-based real time polymerase chain reaction. Results. Pre-treatment with simvastatin significantly reduced cobalt-mediated IL-8 protein secretion (n=3) and sICAM-1 protein secretion (n=2) in THP-1 cells (p-value<0.0001). Work will be undertaken to determine changes in gene expression, the role of TLR4 in these responses and the effect of simvastatin on additional inflammatory markers. Conclusions. Simvastatin significantly reduces cobalt-ion mediated IL-8 and sICAM-1 protein secretion in THP-1 cells. This in-vitro finding demonstrates the potential for simvastatin to reduce recruitment of leukocytes which mediate the deleterious inflammatory processes driving aseptic loosening and pseudotumour formation

Introduction and Objective. An important subset of patients is dissatisfied after total joint arthroplasty (TJA) due to residual functional impairment. This study investigated the assessment of objectively measured step-up performance following TJA, to identify patients with poor functional improvement after surgery, and to predict residual functional impairment during early postoperative rehabilitation. Secondary, longitudinal changes of block step-up (BS) transfers were compared with functional changes of subjective patient reported outcome measures (PROMs) following TJA. Materials and Methods. Patients with end stage hip or knee osteoarthritis (n = 76, m/f = 44/32; mean age = 64.4 standard deviation 9.4 years) were measured preoperatively and 3 and 12 months postoperatively. PROMs were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscore. BS transfers were assessed by wearable-derived measures of time. In our cohort, subgroups were formed based on either 1) WOMAC function score or 2) BS performance, isolating the worst performing quartile (impaired) of each measure from the better performing others (non-impaired). Subgroup comparisons were performed with the Man-Whitney-U test and Wilcoxon Signed rank test resp. Responsiveness was calculated by the effect size, correlations with Pearson's correlation coefficient. A regression analysis was conducted to investigate predictors of poor functional outcome. Results. WOMAC function scores were strongly correlated to WOMAC pain scores (Pearson's r=0.67–0.84) and moderately correlated to BS performance (Pearson's r = 0.31–0.54). Prior to surgery, no significant differences for WOMAC function scores and BS performance were found between the impaired and non-impaired subgroups. One year after TJA, our cohort performed significantly better at WOMAC and BS with largest effect size for the non-impaired subgroups (0.62 and 0.43 resp.) At 12 months postop, 56% of patients allocated to the impaired subgroup defined by WOMAC, represented the impaired subgroup defined by BS. Allocation to the impaired subgroup at 3 months postop, raised the odds for belonging to the impaired subgroup at 12 months for WOMAC with an odds ratio=19.14 (67%) and for BS with an odds ratio=4.41 (42%). Conclusions. Assessment of BS performance following TJA reveals residual functional impairment that is not captured by pain-dominated PROMs. Its additional use may help to early identify those patients at risk for a poor outcome

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 osteolysis caused by immune-mediated inflammation responses to wear debris generated from the materials used in the THR implant. Therefore, by understanding the biological steps by which biomaterials cause immune-mediated reactions it should be possible to prevent them in the future thereby reducing the number of costly revision surgeries required. Materials and Methods. The human osteoblast-like cell line (MG-63) was seeded at a density of 100,000 cell per well of a 6-well plate and treated with and increasing doses (0.5, 5, and 50mm. 3. per cell) of cobalt-chromium (CoCr) particles generated on a six-station pin-on-plate wear generator or commercially available ceramic oxide nanopowders (Al. 2. O. 3. and ZrO. 2. ) for 24 hours. TNF-alpha was used as a positive control and untreated cells as a negative control. Cells were then analysed by transmission electron microscopy (TEM) to determine whether the osteoblasts were capable of phagocytosing these biomaterials. MG-63 cells were used in conjunction with trypan blue and the XTT Cell Proliferation II Kit to assess cytotoxicity of the biomaterials investigated. Cells supernatants were also collected and analysed by enzyme-linked immunosorbant assay (ELISA) to investigate changes in pro-inflammatory protein secretion. Protein extracted from lysed cells was used for western blotting analysis to investigate RANKL protein expression to determine changes to osteolytic activation. Lysed cells were also used for RNA extraction and subsequent cDNA synthesis for real-time quantitative polymerase chain reaction (RT-qPCR) in order to assess changes to pro-inflammatory gene expression. Results. There was no significant change to cellular viability or proliferation in the osteoblasts treated with CoCr, Al. 2. O. 3. or ZrO. 2. when compared to the untreated negative control. TEM images showed clear and distinct intracellular vesicles within the cell cytoplasm which contained CoCr, Al. 2. O. 3. and ZrO. 2. RANKL expression increased at 5 and 50mm. 3. per cell CoCr and 50mm. 3. per cell Al. 2. O. 3. and ZrO. 2. Pro-inflammatory protein secretion of CXCL10, IL-8, and IL-6 all significantly increased at 50mm. 3. per cell CoCr, Al. 2. O. 3. , and ZrO. 2. Similarly to the protein secretion, CXCL10, IL-8, and IL-6 gene expression was significantly upregulated at 50mm. 3. per cell CoCr, Al. 2. O. 3. , and ZrO. 2. Conclusions. Increased in vitro RANKL expression in response to CoCr, Al. 2. O. 3. , and ZrO. 2. may result in disruption of bone metabolism and lead to osteolysis which can contribute to aseptic loosening in vivo. Significant increases in IL-6 are particularly important because as well as being a pro-inflammatory cytokine, IL-6 is also secreted by osteoblasts in order to stimulate mature osteoclast formation to mediate bone breakdown. CXCL10 and IL-8 are chemotactic cytokines and increased secretion in response to implant biomaterials can contribute to ongoing pro-inflammatory responses through the recruitment of monocytes and neutrophils respectively. This is interesting as in vivo data demonstrates increased cellular infiltrate in patients experiencing responses to implant materials. Overall, these findings show clear immune activation as well as altered metabolism of MG-63 osteoblast cells in response to implant wear debris which is in agreement with in vivo clinical reports

Osteoarthritis is a slowly progressive disease which includes the intervention of several cytokines and macrophage metalleinoproteinases reaction, leading to the degradation of the local cartilage but also having an impact on the serum acute phase proteins (APPs). Subsequently, biomarkers seem to be essential to estimate its progression and the need for any surgical intervention such as total arthroplasty, but also can be used as therapeutic agents. Recently, among APPs, fetuin-A drew attention regarding its possible anti-inflammatory role in animal models but also as a therapeutic agent in the inflammatory joint disease in clinical trials. The purpose of this study is to investigate the possible attenuating role of the intra-articular administration of Fetuin-A in post-traumatic induced secondary osteoarthritis in rats, and also its effect on the systematic levels of IL-2,4,7, BMPs 2,4,7, CRP and Fetuin-A. 30 male Sprague Dawley rats were separated in two groups where post-traumatic osteoarthritis was induced surgically by Anterior Cruciate Ligament Transection and the transection of the Medial Collateral Ligament of the right knee. In the Control Group, only surgical intervention took place. In Fetuin Group, along with the induction of osteoarthritis, a single dose of bovine fetuin was administrated intra-articularly intra-operatively in 5 and 8 weeks of the experimental protocol. Both groups were examined for 8 weeks. The levels of interleukins, bone morphogenetic proteins, Fetuin-A and C-Reactive Protein were evaluated by ELISA of peripheral blood in three time periods: preoperatively, 5 and 8 weeks post-operatively. Knee osteoarthritic lesions were classified according to Osteoarthritis Research Society International Grading System and Modified Mankin Score, by histologic examination. IL-2 levels were significantly decreased in the Fetuin Group. No statistical difference was signed on the levels of IL-7, BMP-2,4,7 and Fetuin-A between the two groups. CRP levels were significantly increased in the Fetuin Group in 5 weeks of the experiment. Fetuin Group signed better scores according to the OARSI classification system and Modified Mankin Score, without any statistical significance. Intra-articular administration of Fetuin-A restrictively affected the progression of post-traumatic arthritis in rats, as only the levels of IL-2 were decreased as well as limited osteoarthritic lesions were observed on the Fetuin Group