The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase.Aims
Methods
Critical-sized bone defects remain challenging in the clinical setting. Autologous bone grafting remains preferred by clinicians. However, the use of autologous tissue is associated with donor-site morbidity and limited accessibility to the graft tissue. Advances in the development of synthetic bone substitutes focus on improving their osteoinductive properties. Whereas osteoinductivity has been demonstrated with ceramics, it is still a challenge in case of polymeric composites. One of the approaches to improve the regenerative properties of biomaterials, without changing their synthetic character, is the addition of inorganic ions with known osteogenic and angiogenic properties. We have previously reported that the use of a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50% beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating of the TCP particles can enhance the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) (3). To further support the regenerative properties of these scaffolds, inorganic ions with known angiogenic properties, copper or cobalt, were added to the coating solution. β-TCP particles were immersed in a zinc and copper or zinc and cobalt solution with a concentration of 15 or 45 mM. 3D porous scaffolds composed of 1000PEOT70PBT30 and pure or coated β-TCP were additively manufactured by 3D fibre deposition. The osteogenic and angiogenic properties of the fabricated scaffolds were tested
This study compared the cobalt and chromium serum ion concentration of patients treated with two different metal-on-metal (MoM) hinged total knee arthroplasty (TKA) systems, as well as a titanium nitride (TiN)-coated variant. A total of 63 patients (65 implants) were treated using either a MoM-coated (n = 29) or TiN-coated (n = 7) hinged TKA (GenuX mobile bearing, MUTARS; Implantcast, Germany) versus the BPKS (Brehm, Germany) hinged TKA (n = 27), in which the weight placed on the MoM hinge is diffused through a polyethylene (PE) inlay, reducing the direct load on the MoM hinge. Serum cobalt and chromium ion concentrations were assessed after minimum follow-up of 12 months, as well as functional outcome and quality of life.Aims
Methods
Metal allergy in knee arthroplasty patients is a controversial topic. We aimed to conduct a scoping review to clarify the management of metal allergy in primary and revision total knee arthroplasty (TKA). Studies were identified by searching electronic databases: Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and Embase, from their inception to November 2020, for studies evaluating TKA patients with metal hypersensitivity/allergy. All studies reporting on diagnosing or managing metal hypersensitivity in TKA were included. Data were extracted and summarized based on study design, study population, interventions and outcomes. A practical guide is then formulated based on the available evidence.Aims
Methods
The anatomic dual mobility (ADM) technology utilized a monoblock cobalt chromium acetabular component. However, design limitations conferred difficulties controlling orientation during component insertion and inability to confirm full implant seating; the solution resulted in the creation of the modular dual mobility (MDM). The modular implant combines a standard titanium acetabular component and a cobalt chromium liner insert. Due to the metal-on-metal interface on MDM implants, fretting and corrosion releasing metal ions like previous metal-on-metal THA implants, were a concern. This study prospectively reviewed metal ions (cobalt, chromium and titanium) on patients who were at least 1 year post MDM implantation and compared them to patients with an ADM implant and evaluated radiographic seating of the components. All patients with ADM and MDM implants underwent evaluation of metal ions (cobalt, chromium and titanium) at their one year follow-up appointment. Radiographic evaluation for acetabular polar gaps was performed. Elevated metal ions were determined using standard laboratory ranges. Differences in baseline demographics were assessed using the Mann Whitney-U test and Fishers's exact test. Differences in metal ions and implant type were compared using the Fisher's exact tests.Introduction
Methods
Currently, different techniques to evaluate the biocompatibility of orthopaedic materials, including two-dimensional (2D) cell culture for metal/ceramic wear debris and floating 2D surfaces or three-dimensional (3D) agarose gels for UHMWPE wear debris, are used. Moreover, cell culture systems evaluate the biological responses of cells to a biomaterial as the combined effect of both particles and ions. We have developed a novel cell culture system suitable for testing the all three type of particles and ions, separately. The method was tested by evaluating the biological responses of human peripheral blood mononuclear cells (PBMNCs) to UHMWPE, cobalt-chromium alloy (CoCr), and Ti64 alloy wear particles. Clinically relevant sterile UHMWPE, CoCr, and Ti64 wear particles were generated in a pin-on-plate wear simulator. Whole peripheral blood was collected from healthy human donors (ethics approval BIOSCI 10–108, University of Leeds). The PBMNCs were isolated using Lymphoprep (Stemcell, UK) and seeded into the wells of 96-well and 384-well cell culture plates. The plates were then incubated for 24 h in 5% (v/v) CO2 at 37°C to allow the attachment of mononuclear phagocytes. Adherent phagocytes were incubated with UHMWPE and CoCr wear debris at volumetric concentrations of 0.5 to 100 µm3 particles per cell for 24 h in 5% (v/v) CO2 at 37°C. During the incubation of cells with particles, for each assay, two identical plates were set up in two configurations (one upright and one inverted). After incubation, cell viability was measured using the ATPlite assay (Perkin Elmer, UK). Intracellular oxidative stress was measured using the DCFDA-based reactive oxygen species detection assay (Abcam, UK). TNF-α cytokine was measured using sandwich ELISA. DNA damage was measured by alkaline comet assay. The results were expressed as mean ± 95% confidence limits and the data was analysed using one-way ANOVA and Tukey-Kramer post-hoc analysis. Cellular uptake of UHMWPE, CoCr and Ti64 particles was confirmed by optical microscopy. PBMNCs incubated with UHMWPE particles did not show any adverse responses except the release of significant levels of TNF-α cytokine at 100 µm3 particles per cell, when in contact with particles. PBMNCs incubated with CoCr wear particles showed adverse responses at high particle doses (100 µm3 particles per cell) for all the assays. Moreover, cytotoxicity was observed to be a combined effect of both particles and ions, whereas oxidative stress and DNA damage were mostly caused by ions. Ti64 wear particles did not show any adverse responses except cytotoxicity at high particle doses (100 µm3 particles per cell). Moreover, this cytotoxicity was mostly found to be a particle effect. In conclusion, the novel cell culture system is suitable for evaluating the biological impact of orthopaedic wear particles and ions, separately.Methods
Results and Discussion
It is well-known that wear debris generated by metal-on-metal hip replacements leads to aseptic loosening. This process starts in the local tissue where an inflammatory reaction is induced, followed by an periprosthetic osteolysis. MOM bearings generate particles as well as ions. The influence of both in human bodies is still the subject of debate. For instance hypersensitivity and high blood metal ion levels are under discussion for systemic reactions or pseudotumors around the hip replacement as a local reaction. The exact biopathologic mechanism is still unknown. The aim of this study was to investigate the impact of local injected metal ions and metal particles. We used an established murine inflammation model with Balb/c mice and generated three groups. Group PBS (control group, n=10) got an injection of 50µl 0.1 vol% PBS-suspension, Group MI (Metal-ion, n=10) got an injection of 50µl metal ion suspension at a concentration of 200µg/l and Group MP (Metal-particles, n=10) got an injection of 50µl 0.1 vol% metal particle suspension each in the left knee. After incubation for 7 days the mice were euthanized and the extraction of the left knee ensued. Followed by immunhistochemical treatment with markers of inflammation that implied TNFα, IL-6, IL-1β, CD 45, CD 68, CD 3, we counted the positive cells in the synovial layer in the left knees by light microscopy, subdivided into visual fields 200× magnified. The statistical analysis was done with Kruskal-Wallis test and a post hoc Bonferroni correction.Introduction
Material and Methods
Wear induces osteolysis leading to periprosthetic bone loss and TJA loosening. Inflammatory immune cells can form an aggressive interface membrane activating osteoclasts. The current study shows the effect of metal particles and ions triggering cellular responses. Blood samples from primary and revision TJA were analysed for systemic inflammation. PBMCs were cultured on different implant materials. Cellular response was monitored by qRT-PCR. Furthermore, cells were exposed to increasing concentrations of metal particles (10-7 and 10–8 particles/ml) and CoCl2 (50 µM and 100 µM). Cellular response was measured using WST-1 reduction, MitoSox-fluorescence and TUNEL-staining. Cobalt ion influx into osteoblasts was measured using FURA2-staining, cellular effects for HIF-1alpha and qRT-PCR. No inflammatory parameters were detected in patients' blood from primary and revision TJA. Short inflammatory reaction of their PBMCs was observed in in vitro culture on ceramic implants, whereas there was no such reaction to other tested implant martials. In MM6 and Jurkat cells only metal ions induced oxidative stress but did not significantly reduce cell viability. An increase in HIF1-alpha was observed in tissue containing large amounts of metal wear in comparison to plastic wear containing tissues and OA synovial tissue without wear particles. Cobalt ions were stored by osteoblasts via a calcium channel inducing hypoxia. This effect could be blocked using a TRPM blocking agent. Ceramic induces a short inflammatory response that may induce periprosthetic inflammation. Ionic Cobalt induces oxidative stress and hypoxia. Ionic metal exerts a more intense reaction on cells than particles.
Metal-on-metal bearings (MoM) saw an increase in global utilisation in the last decade. This peaked in 2008 in the US, with approximately 35% of bearings being hard-on-hard (metal-on-metal, or ceramic-on-ceramic). Beginning in 2008, reports began to surface regarding local soft tissue reactions and hypersensitivity to MoM bearings. A major implant manufacturer recalled a resurfacing device in 2010 after national joint registries demonstrated higher than expected revision rates. Patients with painful MoM bearings are a difficult diagnostic challenge. The surgeon must go back to basic principles, perform a complete history and physical exam, obtain serial radiographs and basic blood work (ESR, CRP) to rule out common causes of pain and determine if the pain is, or is not, related to the bearing. The Asymptomatic MoM Arthroplasty: Patients will present for either routine follow up, or because of concerns regarding their bearing. It is important to emphasise that at this point the vast majority of patients with a MoM bearing are indeed asymptomatic and their bearings are performing well. The surgeon must take into account: a) which specific implant are they dealing with and what is its track record; b) what is the cup position; c) when to perform metal ion testing; d) when to perform further soft tissue imaging (MARS MRI, Ultrasound); e) when to discuss possible surgery. Painful MoM THA causes not related to the bearing couple: These can be broken down into two broad categories. Causes that are Extrinsic to the hip include spine, vascular, metabolic and malignancy. Causes that are Intrinsic to the hip can either be Extracapsular or Intracapsular. Painful MoM THA causes related to the bearing couple: There are now described a number of possible clinical scenarios and causes of pain that relate to the MoM bearing couple itself: A) Local hypersensitivity reaction without a significant soft tissue reaction; B) Local hypersensitivity reaction with a significant soft tissue reaction; C) Impingement and soft tissue pain secondary to large head effect. Factors related to a hypersensitivity reaction: Some patients, and prostheses, seem to be at a higher risk of developing issues following a MoM bearing, although our understanding of the interplay of these factors is still in evolution: patients at risk include all women and patients with smaller component sizes. Implant factors play a role with some implants having higher wear rates and being more prone to corrosion. Special tests: There is ongoing confusion related to the relative value of the various special tests that patients with a painful MoM undergo. A) Metal
Recent studies have demonstrated that implant-specific blood metal ion thresholds exist in unilateral and bilateral metal-on-metal (MoM) hip arthroplasty patients, with these thresholds being most effective for identifying patients at low-risk of adverse reactions to metal debris (ARMD). We investigated whether these new blood metal ion thresholds could effectively identify patients at risk of ARMD in an external cohort of MoM hip arthroplasty patients. We performed a validation study involving 803 MoM hip arthroplasties implanted in 710 patients at three European centres (323=unilateral Birmingham Hip Resurfacing (BHR); 93=bilateral BHR; 294=unilateral Corail-Pinnacle). All patients underwent whole blood metal ion sampling. Patients were divided into those with ARMD (revised for ARMD or ARMD on imaging; n=75), and those without ARMD (n=635). Previously devised implant-specific blood metal ion thresholds (cobalt=2.15μg/l for unilateral BHR; maximum cobalt or chromium=5.5μg/l for bilateral BHR; cobalt=3.57μg/l for unilateral Corail-Pinnacle) were applied to the validation cohort, with receiver operating characteristic curve analysis used to establish the discriminatory characteristics for each respective threshold. The area under the curve, sensitivity, specificity, positive predictive value and negative predictive value for distinguishing between patients with and without ARMD for each implant-specific threshold were respectively: unilateral BHR=89.4% (95% CI=82.8%-96.0%), 78.9%, 86.7%, 44.1%, 96.9%; bilateral BHR=89.2% (95% CI=81.3%-97.1%), 70.6%, 86.8%, 54.5%, 93.0%; unilateral Corail-Pinnacle=76.9% (95% CI=63.9%-90.0%), 65.0%, 85.4%, 24.5%, 97.1%. The 7μg/l UK MHRA threshold missed significantly more patients with ARMD compared with the implant-specific thresholds (4.9% vs. 2.8%; p=0.0003). This external multi-centre validation study has confirmed that MoM hip arthroplasty patients with blood metal ion levels below newly devised implant-specific thresholds have a low-risk of ARMD. Compared to implant-specific thresholds, the currently proposed fixed MHRA threshold missed more patients with ARMD. We recommend using implant-specific thresholds over fixed thresholds when managing MoM hip arthroplasty patients.
Increased revision rates and early failure of Metal-on-Metal (MoM) hip replacements are often due to adverse reaction to metal debris (ARMD). ARMD describes numerous symptoms in patients such as pain, osteolysis and soft tissue damage. Cobalt is a major component of MoM joints and can initiate an immune response via activation of the innate immune receptor Toll-like receptor 4 (TLR4). This leads to increased secretion of inflammatory cytokines e.g. interleukin-8 (IL-8). This study investigates whether TLR4-specific antagonists inhibit the inflammatory response to cobalt using IL-8 gene expression and protein secretion as a marker of TLR4 activation. MonoMac 6 (MM6) cells, a human macrophage cell line, were treated with TLR4-specific antagonists followed by 0.75mM of cobalt chloride. Lipopolysaccharide (LPS), a known TLR4 agonist was used as a positive control. Enzyme-linked immunosorbent assay (ELISA) was used to assess IL-8 protein secretion and real time- polymerase chain reaction (RT-PCR) allowed quantification of IL-8 gene expression.Background
Methods
The CoCrMo large bearings had shown a high failure rate, because of metal ion and particle release. Alumina matrix composite (AMC) ball heads have shown to mitigate such phenomena. The aim of this study was to investigate the leaching properties of AMC clinically as well as experimentally. Two patient groups were compared: a control group (n=15) without any implant (Controls) and 15 Patients with unilateral treatment with Biolox delta ceramic-on-ceramic (CoC). Whole-blood samples of Controls and Patients (after 3 and 12 months from treatment with CoC) were measured by means of trace element analysis using a HR-ICPMS. The leaching behaviour of BIOLOX delta was also analysed in-vitro: five Biolox delta heads and five CoCrMo heads were immersed in serum for seven days at 37°C. Aluminium, cobalt, chromium and strontium were detected based on HR-ICPMS.Background
Methods
Metal on metal bearings are used especially in hip resurfacing. On the one hand, small bone preserving implants can be used. On the other hand recent studies found a variety of local and systemic side effects, for instance the appearance of pseudotumors, that are explained by pathologic biological reaction of the metal wear debris. The detailed mechanisms are still not understood until now. Thus it was the aim of this study to investigate the local reaction of metal wear particles and metal ions in a murine model. The hypothesis was that mainly metal ions provoke adverse histopathological reactions in vivo. Three groups, each with 10 Balb / c mice were generated. Group A: injection of a 50 µl metal ion suspension at a concentration of 200 µg / l in the left knee. Group B: injection of a 50 µl 0,1 vol% metal particle suspension into the left knee joint. Group C (control group): injection of a 50 µl of 0,1 vol% PBS-suspension in the left knee. Incubation for 7 days, followed by euthanasia of the animals by intracardiac pentobarbital. The left and right knee, the lungs, kidneys, liver and spleen were removed. Histologic paraffin sections in 2 microns thickness were made, followed by HE (overview staining) and Movat (Pentachrom staining) staining. The histologic analysis was a done by a light microscopic evaluation of the subdivided visual fields at 200× magnification.Introduction
Material and Methods
Femoral heads made from zirconia-toughened alumina (ZTA) are the most advanced bioceramic available for total hip arthroplasty. ZTA's superior mechanical properties result from the polymorphic transformation of its zirconia (ZrO2) phase in the presence of a propagating crack. BIOLOX®Introduction
Materials and Methods
We have previously observed an increase in total bone mineral density and reduced bone turnover (TRAP5b and osteocalcin) in patients with well-functioning metal-on-metal hip resurfacing (MOMHR). Here, we provide data to support the hypothesis that osteoclast differentiation and function is altered in this patient population, and that this effect is transferrable through their serum. Patients with well-functioning MOMHR (cases, n=18) at a median follow-up of 8 years were individually matched for gender, age and time-since-surgery to a low-exposure group consisting of patients with THA (controls, n=18). The monocyte fraction of patient peripheral blood was isolated and differentiated into osteoclasts on dentine wafers using RANKL and M-CSF supplemented media (osteoclastogenic media, OM). Cultures were monitored for the onset of resorption, at which point the cells were treated with OM, autologous serum or serum from matched MOMHR/THA donors, all supplemented with RANKL and M-CSF. At the end of the culture, cells were TRAP-stained and quantified using CellD Software Package, Olympus. When cells were differentiated in standard osteoclastogenic media, the resorbing ability of osteoclasts derived from MOMHR patients was reduced 22%(p<0.0079) compared to THA. The resorbing ability of osteoclasts generated from MOMHR patients and differentiated in autologous serum was reduced 33%(p<0.0001), whilst matched THA serum caused a smaller reduction of 14%(p<0.01). When cells derived from THA patients were differentiated in autologous serum, the resorbing ability of osteoclasts was similarly reduced by 35%(p<0.0001), whilst the matched MOMHR serum also caused a reduction of 21%(p<0.0001). This data suggests that prior exposure to higher circulating Co and Cr in patients with MOMHR reduces osteoclastogenesis, and that the detrimental effect on the functionality of mature osteoclasts is transferable through the serum. This has implications for systemic bone health of patients with MOMHR or modular taper junctions.
We investigated whether blood metal ions could effectively identify bilateral metal-on-metal hip patients at risk of adverse reactions to metal debris (ARMD). This single-centre, prospective study involved 235 patients (185 bilateral Birmingham Hip Resurfacings (BHRs) and 50 bilateral Corail-Pinnacles) undergoing whole blood metal ion sampling (mean time=6.8 years from latest implant to sampling). Patients were divided into ARMD (revised or ARMD on imaging; n=40) and non-ARMD groups (n=195). Metal ion parameters (cobalt; chromium; maximum cobalt or chromium; cobalt-chromium ratio) were compared between groups. Optimal metal ion thresholds for identifying ARMD patients were determined using receiver operating characteristic (ROC) analysis, which compares the performance of different tests using the area under the curve (AUC) (higher AUC=more discriminatory).Introduction
Patients and methods
Introduction. Various anti-infective agents can be added to the surface of orthopaedic implants to actively kill bacteria and prevent infection. Silver (Ag) is a commonly used agent in various anti-infective applications. Silver disrupts bacterial membranes and binds to bacterial DNA and to the sulfhydryl groups of metabolic enzymes in the bacterial electron transport chain, thus inactivating bacterial replication and key metabolic processes. Recently we are implanting Silver coated megaprosthesis for the treatment of post-traumatic septic non unions/bone defects and for infected hip or knee prosthesis revision. We treat these complications utilizing a two steps procedure: 1° step: devices removal, resection, debridment and antibiotic spacer implantation; 2° step: spacer removal and megaprosthesis implantation. This technique produce a reactive pseudosynovial membrane, well known in traumatology (Masquelet technique), following the Chamber Induction Technique principles. This chamber creates the perfect environment in which implant the prosthesis with safety. We are nowadays investigating if this membrane could optimize the Silver antimicrobical effects reducing the Silver ions dispersion and reducing toxicity on the human body. Objectives. The aim of this study is to perform a review of the literature about Silver coated implants in Orthopaedics and Trauma and to analyze our cases treated with this implants in order to measure their efficacy and the ion dispersion in urine and blood. Methods. We performed a literature review using the universally validated search engines in the biomedical field: PubMed / Medline, Google Scholar, Scopus, EMBASE. The keywords used were: “Silver”, “Silver coating”, “Silver surface”, “were crossed with “Prosthesis”, “Megaprosthesis”, “Infection”, “Sepsis”, “Revision”. We also analized all our patients treated with Silver coated implants measuring Silver dose in blood and urine before implantation, 1 day after implantation and then after 15 days, 3,6,12,24,36 months. Results. The search led to 468 items, of these were considered only article in English with full text available. We found 1 in vitro study, 1 animal study and 2 human studies. The animal study showed a reduction in periprosthetic infection from 47% to 7%, 1 human study in Oncology application of megaprosthesis showed a reduction of septic complications from 17,6% to 5,9%. Te other human study demonstrated that Silver surface implants don't have toxicity cause the blood level of silver
There are many guidelines that help direct the management of
patients with metal-on-metal (MOM) hip arthroplasties. We have undertaken
a study to compare the management of patients with MOM hip arthroplasties in
different countries. Six international tertiary referral orthopaedic centres were
invited to participate by organising a multi-disciplinary team (MDT)
meeting, consisting of two or more revision hip arthroplasty surgeons
and a musculoskeletal radiologist. A full clinical dataset including
history, blood tests and imaging for ten patients was sent to each
unit, for discussion and treatment planning. Differences in the
interpretation of findings, management decisions and rationale for
decisions were compared using quantitative and qualitative methods.Aims
Methods
Systemic levels of metal ions are surrogate markers of in-vivo wear of metal-on-metal hip resurfacings (MoMHRA). The wear-related generation of metal ions is associated with component size and positioning but also with design specific features such as coverage angle, clearance, metallurgy and surface technology. The objective of the study was to investigate whether a hip resurfacing design (ACCIS) with TiNb engineered bearing surfaces would generate less chromium (Cr) and cobalt (Co) ions during and after the run-in phase of wear and whether Ti ions could be detected indicating wear of the coating.INTRODUCTION
OBJECTIVES
Between April 2008 and February 2012, we implanted 159 large-diameter MOM stemmed THA with head diameters of 38–50mm. There were 6–38mm, 22–40mm, 42–42mm, 42–44mm, 24–46mm, 13–48mm, 4–50mm, 5–52mm, and one-54mm heads implanted in 138 patients (21 males and 117 females). The pre-operative diagnoses included: 120 OAs, 12
