• 3D printing
• additive manufacturing
• bone tissue engineering
• environment-responsive
• orthopedic implants
• surface modification

• CoCr
• graphene oxide
• hematological analysis
• hyaluronic acid
• inflammatory response
• wear–corrosion particles

• PRE2019-090122 Ministerio de Ciencia e Innovación
• RTI2018-101506-B-C31 Ministerio de Ciencia e Innovación
• RTI2018-101506-B-C32 Ministerio de Ciencia e Innovación
• RTI2018-101506-B-C33 Ministerio de Ciencia e Innovación

• NLRP3 inflammasome
• human osteoblasts
• joint replacement
• metallic particles
• osteolysis

• Humans
• Cells, Cultured
• Gene Expression Regulation/drug effects
• Inflammasomes/metabolism
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• NLR Family, Pyrin Domain-Containing 3 Protein/genetics
• Osteoblasts/metabolism
• Osteoblasts/drug effects
• Osteoblasts/immunology
• Signal Transduction/drug effects
• Tumor Necrosis Factor-alpha/metabolism

• Inflammasomes/metabolism
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• Caspase 1/metabolism
• Cell Line
• Arthroplasty
• Interleukin-1beta/metabolism

• Corrosion
• Inflammation
• Metal hypersensitivity reaction
• Osteolysis
• Wear debris

• Animals
• Arthroplasty, Replacement, Hip/adverse effects
• Lymphocyte Activation
• Osteolysis/etiology
• Metals
• Cytokines
• Inflammation/complications
• Hypersensitivity/etiology

• CoCr28Mo6 alloy
• Deep rolling
• Hardness gradient
• Phase transformation
• Residual stress
• Surface integrity
• Wear

• chromium
• cobalt
• cytokines
• human myoblast
• inflammation

• inflammatory cytokines
• metal ion concentration
• periprosthetic tissue
• postmortem retrieval analysis
• synovial fluid
• total knee arthroplasty

• Arthroplasty, Replacement, Knee/adverse effects
• Chromium
• Cobalt
• Humans
• Metals
• Prospective Studies

• R01 AR047904 NIAMS NIH HHS

Arthroplasty ranks among the greatest achievements of surgical medicine, with total hip replacement termed “the operation of the century.” Despite its wide success, arthroplasty bears risks, such as local reactions to implant derived wear and corrosion products. Prevalence of allergies across Western society increases and along the number of reported hypersensitivity reactions to orthopedic implant materials. In this context the main focus is on delayed hypersensitivity (DTH). This mechanism is mainly attributed to T cells and an overreaction of the adaptive immune system. Arthroplasty implant materials are in direct contact with bone marrow (BM), which is discussed as a secondary lymphoid organ. However, the mechanisms of sensitization toward implant wear remain elusive. Nickel and cobalt ions can form haptens with native peptides to activate immune cell receptors and are therefore common T helper allergens in cutaneous DTH. The rising prevalence of metal-related allergy in the general population and evidence for the immune-modulating function of BM allow for the assumption hypersensitivity reactions could occur in peri-implant BM. There is evidence that pro-inflammatory factors released during DTH reactions enhance osteoclast activity and inhibit osteoblast function, an imbalance characteristic for osteolysis. Even though some mechanisms are understood, hypersensitivity has remained a diagnosis of exclusion. This review aims to summarize current views on the pathomechanism of DTH in arthroplasty with emphasis on BM and discusses recent advances and future directions for basic research and clinical diagnostics.

• arthroplasty
• bone marrow
• delayed type hypersensitivity
• immune cells
• memory T cells
• metal

• Interleukin-8
• allergy and immunology
• arthroplasty
• contact
• cytokines
• hip
• hypersensitivity
• replacement

• arthroplasty
• complication
• hip
• metal-on-metal
• revision

• FTIR imaging
• adverse local tissue reaction
• corrosion product
• total hip replacement
• wear debris

Adverse Reaction to Metal Debris (ARMD) is a major reason for revision surgeries in patients with metal-on-metal (MoM) hip replacements. Most failures are related to excessively wearing implant producing harmful metal debris (extrinsic factor). As ARMD may also occur in patients with low-wearing implants, it has been suggested that there are differences in host-specific intrinsic factors contributing to the development of ARMD. However, there are no studies that have directly assessed whether the development of ARMD is actually affected by these intrinsic factors.

We included all 29 patients (out of 33 patients) with sufficient data who had undergone bilateral revision of ASR MoM hips (58 hips) at our institution. Samples of the inflamed synovia and/or pseudotumour were obtained perioperatively and sent to histopathological analysis. Total wear volumes of the implants were assessed. Patients underwent MARS-MRI imaging of the hips preoperatively. Histological findings, imaging findings and total wear volumes between the hips of each patient were compared.

The difference in wear volume between the hips was clinically and statistically significant (median difference 15.35 mm³, range 1 to 39 mm³, IQR 6 to 23 mm³) (p < 0.001). The median ratio of total wear volume between the hips was 2.0 (range 1.09 to 10.0, IQR 1.67 to 3.72). In majority of the histological features and in presence of pseudotumour, there were no differences between the left and right hip of each patient (p > 0.05 for all comparisons). These features included macrophage sheet thickness, perivascular lymphocyte cuff thickness, presence of plasma cells, presence of diffuse lymphocytic infiltration and presence of germinal centers.

Despite the significantly differing amounts of wear (extrinsic factor) seen between the sides, majority of the histological findings were similar in both hips and the presence of pseudotumour was symmetrical in most hips. As a direct consequence, it follows that there must be intrinsic factors which contribute to the symmetry of the findings, ie. the pathogenesis of ARMD, on individual level. This has been hypothesized in the literature but no studies have been conducted to confirm the hypothesis. Further, as the threshold of metal debris needed to develop ARMD appears to be largely variable based on the previous literature, it is likely that there are between-patient differences in these intrinsic factors, ie. the host response to metal debris is individual.

The online version of this article (10.1186/s12891-019-2578-0) contains supplementary material, which is available to authorized users.

• ALVAL
• ARMD
• ASR
• Host response
• Metal-on-metal
• Patient susceptibility
• Pseudotumor
• Pseudotumour

• Amorphous carbon film
• Artificial femoral head
• Biocompatibility
• Total hip arthroplasty

• ROS
• arthroplasty
• cobalt particles + ions
• immune cells
• superoxide

Clinicians are often faced with the decision whether to revise a painful total knee replacement in patients who have chronic vague pain with no apparent explanation. A sensitive metal testing assay called the lymphocyte stimulation test has been used to detect nickel sensitization in patients with orthopedic implants. We hypothesize that nickel sensitization plays a role in the pathology of failed joint arthroplasty in patients with unexplained dissatisfaction.

32 patients with symptomatic total knee arthroplasty without obvious mechanical findings were tested prior to revision surgery. 19 nickel-sensitized and 13 non-sensitized patients were compared by cell counts of synovium surgical specimens for CD4⁺ and CD8⁺ cell lines. Patients were then revised with ceramic-coated implants. Secondary evaluation of functional outcomes, range of motion, and pain relief were assessed.

Nickel-sensitive patients showed a statistical increase in CD4⁺ reactivity compared to CD8⁺ reactivity. The ratio of CD4⁺/CD8⁺ T lymphocytes was 1.28 in nickel-sensitive patients versus 0.76 in the control (p = 0.009). There was no difference in functional scores, clinical scores, or range of motion after revision.

This study provides objective data via histological analysis in support of a nickel allergic sensitization in failed arthroplasties where clinical and/or radiographic abnormalities may not be apparent. Biopsy for CD4⁺/CD8⁺ cell counts may provide further proof of the existence of nickel sensitization in lymphocyte stimulation test positive patients, and more importantly, may implore the surgeon to consider low nickel implant design in these patients.

• Ceramic implant
• Failed knee arthroplasty
• Hypersensitivity
• Metal allergy
• Wear byproducts

• Aged
• Arthroplasty, Replacement, Hip/adverse effects
• Chromium/analysis
• Chromium/blood
• Cobalt/analysis
• Cobalt/blood
• Female
• Hip Joint/pathology
• Hip Prosthesis/adverse effects
• Humans
• Male
• Metal-on-Metal Joint Prostheses/adverse effects
• Metals/analysis
• Metals/blood
• Molybdenum/analysis
• Molybdenum/blood
• Prosthesis Failure
• Synovial Fluid/chemistry
• Titanium/analysis
• Titanium/blood

• Competitive research funds of Pirkanmaa Hospital District (representing governmental funding)

• inductively coupled plasma mass spectrometry
• joint fluid
• metal release
• periprosthetic tissue
• total joint replacement

• Aged
• Arthroplasty, Replacement, Hip/adverse effects
• Arthroplasty, Replacement, Hip/instrumentation
• British Columbia/epidemiology
• Case-Control Studies
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Granuloma, Plasma Cell/epidemiology
• Granuloma, Plasma Cell/genetics
• Granuloma, Plasma Cell/immunology
• Granuloma, Plasma Cell/surgery
• Hip Joint/physiopathology
• Hip Joint/surgery
• Hip Prosthesis
• Histocompatibility Antigens Class II/genetics
• Histocompatibility Antigens Class II/immunology
• Humans
• Male
• Metal-on-Metal Joint Prostheses
• Middle Aged
• Prevalence
• Prosthesis Design
• Prosthesis Failure
• Reoperation
• Risk Assessment
• Risk Factors
• Time Factors
• Treatment Outcome

Carbon-based nanomultilayer coatings were deposited on medical-grade Ti₆Al₄V alloy using a magnetron sputtering technique under a graded bias voltage.

• ALTR
• ALVAL
• ARMD
• Adverse reaction to metal debris
• Histopathology
• Metal-on-metal hip replacement
• Wear

• Acetabulum/pathology
• Aged
• Arthroplasty, Replacement, Hip/adverse effects
• Arthroplasty, Replacement, Hip/methods
• Female
• Femur Head/pathology
• Follow-Up Studies
• Hip Joint/metabolism
• Hip Joint/pathology
• Hip Joint/surgery
• Hip Prosthesis/adverse effects
• Humans
• Inflammation/blood
• Inflammation/etiology
• Inflammation/pathology
• Ions/blood
• Male
• Metal-on-Metal Joint Prostheses/adverse effects
• Metals/adverse effects
• Metals/blood
• Middle Aged
• Necrosis/etiology
• Necrosis/pathology
• Prosthesis Failure/adverse effects
• Reoperation/statistics & numerical data
• Retrospective Studies
• Synovial Fluid/chemistry
• Time Factors

• 9N044 Pirkanmaa Hospital District (FI), representing government funding

• Arthroplasty, Replacement, Hip/adverse effects
• Arthroplasty, Replacement, Hip/instrumentation
• Corrosion
• Female
• Hip Prosthesis/adverse effects
• Humans
• Metal-on-Metal Joint Prostheses/adverse effects
• Middle Aged
• Prosthesis Design
• Prosthesis Failure
• Reoperation
• Risk Assessment

• Arthroplasty
• Hypersensitivity reaction
• Implant material

• bone healing
• chemokines
• dioxin
• endocrine disruptors
• environmental toxins
• metal
• volatile organic compound

• ALVAL
• ARMD
• Hip resurfacing
• Metal-on-metal
• Pseudotumour
• Revision

• Arthroplasty, Replacement, Hip/methods
• Biomarkers
• Chromium
• Cobalt
• Hip Prosthesis
• Humans
• Metals
• Prosthesis Failure

• TiO2 nanoparticles
• blood protein
• cytoxicity
• hydroxyapatite
• inflammatory response
• nanotoxicology
• oxidative stress
• wear debris particles

• biology
• implant

• Cobalt
• Metal ions
• Metal-on-metal
• Resurfacing
• Total hip arthroplasty

• Arthroplasty, Replacement, Hip/adverse effects
• Arthroplasty, Replacement, Hip/instrumentation
• Chromium/blood
• Cobalt/blood
• Female
• Hip Prosthesis/adverse effects
• Humans
• Ions/blood
• Male
• Middle Aged
• Postoperative Complications/blood
• Prosthesis Design
• Retrospective Studies
• Time Factors

• Hip
• metal
• pseudotumor
• replacement
• total hip arthroplasty

Hips with metal-on-metal total hip arthroplasty (MoM THA) have a high rate of adverse local tissue reactions (ALTR), often associated with hypersensitivity reactions. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measures tissue perfusion with the parameter Ktrans (volume transfer constant of contrast agent). Our purpose was 1) to evaluate the feasibility of DCE-MRI in patients with THA and 2) to compare DCE-MRI in patients with MoM bearings with metal-on-polyethylene (MoP) bearings, hypothesising that the perfusion index Ktrans in hips with MoM THA is higher than in hips with MoP THA.

In this pilot study, 16 patients with primary THA were recruited (eight MoM, eight MoP). DCE-MRI of the hip was performed at 1.5 Tesla (T). For each patient, Ktrans was computed voxel-by-voxel in all tissue lateral to the bladder. The mean Ktrans for all voxels was then calculated. These values were compared with respect to implant type and gender, and further correlated with clinical parameters.

There was no significant difference between the two bearing types with both genders combined. However, dividing patients by THA bearing and gender, women with MoM bearings had the highest Ktrans values, exceeding those of women with MoP bearings (0.067 min⁻¹versus 0.053 min⁻¹; p-value < 0.05) and men with MoM bearings (0.067 min⁻¹versus 0.034 min⁻¹; p-value < 0.001). Considering only the men, patients with MoM bearings had lower Ktrans than those with MoP bearings (0.034 min⁻¹versus 0.046 min⁻¹; p < 0.05).

DCE-MRI is feasible to perform in tissues surrounding THA. Females with MoM THA show high Ktrans values in DCE-MRI, suggesting altered tissue perfusion kinematics which may reflect relatively greater inflammation.

Cite this article: Dr P. E. Beaule. Perfusion MRI in hips with metal-on-metal and metal-on-polyethylene total hip arthroplasty: A pilot stud. Bone Joint Res 2016;5:73–79. DOI: 10.1302/2046-3758.53.2000572.

• DCE-MRI
• Ktrans
• dynamic contrast-enhanced magnetic resonance imaging
• metal-on-metal total hip arthroplasty

Adverse reactions to metal-on-metal (MoM) prostheses are well known from total hip joint resurfacing arthroplasty with elevated serum chrome or cobalt, pain and pseudo tumor formation. It may, however, also be seen after total joint replacement of the trapeziometacarpal joint using MoM articulation, and we present two cases of failure of MoM prostheses due to elevated metal-serum levels in one case and pseudo tumor formation in another case. Furthermore, we suggest a diagnostic algorithm for joint pain after MoM trapeziometacarpal joint replacement based on published experiences from MoM hip prostheses and adverse reactions to metal.

• metal hypersensitivity
• metal-on-metal articulation
• pseudo tumor
• trapeziometacarpal joint osteoarthritis
• trapeziometacarpal joint total joint arthroplasty

We performed a combined approach to identify suspected allergy to knee arthroplasty (TKR): patch test (PT), lymphocyte transformation test (LTT), histopathology (overall grading; T- and B-lymphocytes, macrophages, and neutrophils), and semiquantitative Real-time-PCR-based periprosthetic inflammatory mediator analysis (IFNγ, TNFα, IL1-β, IL-2, IL-6, IL-8, IL-10, IL17, and TGFβ). We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion. They consisted of 20 patients with proven metal sensitization (11 with PT reactions; 9 with only LTT reactivity). Control specimens were from 5 complicated TKR patients without metal sensitization, 12 OA patients before arthroplasty, and 8 PT patients without arthroplasty. Lymphocytic infiltrates were seen and fibrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients. The latter also had marked periprosthetic IFNγ expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief. Our findings demonstrate that combining allergy diagnostics with histopathology and periprosthetic cytokine assessment could allow us to design better diagnostic strategies.

Joint arthroplasty had revolutionized the outcome of orthopaedic surgery. Extensive and collaborative work of many innovator surgeons had led to the development of durable bearing surfaces, yet no single material is considered absolutely perfect. Generation of wear debris from any part of the prosthesis is unavoidable. Implant loosening secondary to osteolysis is the most common mode of failure of arthroplasty. Osteolysis is the resultant of complex contribution of the generated wear debris and the mechanical instability of the prosthetic components. Roughly speaking, all orthopedic biomaterials may induce a universal biologic host response to generated wear débris with little specific characteristics for each material; but some debris has been shown to be more cytotoxic than others. Prosthetic wear debris induces an extensive biological cascade of adverse cellular responses, where macrophages are the main cellular type involved in this hostile inflammatory process. Macrophages cause osteolysis indirectly by releasing numerous chemotactic inflammatory mediators, and directly by resorbing bone with their membrane microstructures. The bio-reactivity of wear particles depends on two major elements: particle characteristics (size, concentration and composition) and host characteristics. While any particle type may enhance hostile cellular reaction, cytological examination demonstrated that more than 70% of the debris burden is constituted of polyethylene particles. Comprehensive understanding of the intricate process of osteolysis is of utmost importance for future development of therapeutic modalities that may delay or prevent the disease progression.

• Debris
• Adverse reaction
• Osteolysis
• Macrophages
• Cytokines
• Chemotaxis
• Polyethylene
• Phagocytosis

• Cobalt-chromium
• Hip implant
• Metal-on-metal
• Wear debris

Hip resurfacing is a conservative type of total hip arthroplasty but its use is controversial, especially in patients with osteonecrosis. The aim of this study was analysis of the clinical and radiographic outcomes of hip resurfacing in patients with osteonecrosis.

Between 2007 and 2008, 30 hip resurfacing arthroplasties were performed due to osteoarthritis secondary to avascular necrosis of femoral head staged as Ficat III and IV.

Patients were qualified to resurfacing arthroplasty when the extent of avascular necrosis using Kerboul’s method was <200° and the angle between avascular necrosis and head-neck junction was >20°. All patients were evaluated clinically and radiologically before and 60 months after the operation.

The mean Harris Hip Score (HHS) score increased from 47.8 to 94.25 (p<0.05). Physical activity level (University of California, Los Angeles activity score – UCLA activity score) improved from 3.7 to 7.55 (p<0.05). No implant migration was observed.

Management of osteonecrosis of the hip with resurfacing arthroplasty seems to be effective in strictly-selected patients.