Orthopaedic Joint Implants Research Articles

New and novel stabilisation approach for radiation-crosslinked Ultrahigh Molecular Weight Polyethylene (XL-UHMWPE) targeted for use in orthopeadic implants

There is a substantial evidence to show that oxidative degradation has a negative impact on the properties and performance of radiation-crosslinked ultra high molecular weight polyethylene (XL-UHMWPE) used as articulating components in orthopaedic joint implants and is the primary cause for their premature failure. In general, high energy radiation is required not only for sterilising the articulating surfaces but also for crosslinking the polymer to improving its mechanical properties and wear resistance thus minimising the extent of formation of wear-particles which are implicated in the aseptic loosening and failure of the implant. To address the oxidative stability of the XL-UHMWPE bearing surfaces, the natural hindered phenol antioxidant, vitamin E, which has been approved by FDA for use in this application, is used to enhance the oxidation resistance of orthopaedic implants, e.g. in tibial bearings. Further, a purified grade of the commercial antioxidant Irganox 1010Ⓡ (pentaerythritol tetrakis(3-[3,5-di tertiary butyl‑4‑hydroxy phenyl]propionate) has also been FDA approved and used in some knee-based systems. In the case of vitamin E, its effectiveness as a potent free radical scavenger, however, presents some issues in respect of the polymer crosslinking process and the homogeneity of its distribution especially during manufacturing processes that involve the infusion of the vitamin into the polymer. The novel approach adopted in this study for the stabilisation of XL-UHMWPE bearing surfaces makes use of graftable polymer-reactive antioxidants (r-AOs) bearing a hindered phenol and also hindered amine moieties. Potentially, these r-AOs can be chemicaly grafted in-situ on the polymer backbone during the radiation-crosslinking process without the need for any additional manufacturing step. The results obtained have demonstrated a substantive stabilisation which can be achieved with these r-AOs. This was shown to be the case in all the XL-UHMWPE samples tested here which were manufactured according to a methodology typically used in the commercial production and crosslinking (by gamma- or electron-beam) of UHMWPE-based implants.

Improving the Tribological Properties and Biocompatibility of Zr-Based Bulk Metallic Glass for Potential Biomedical Applications.

Zr-based bulk metallic glasses (Zr-BMGs) are potentially the next generation of metallic biomaterials for orthopaedic fixation devices and joint implants owing to their attractive bulk material properties. However, their poor tribological properties and long-term biocompatibility present major concerns for orthopaedic applications. To this end, a novel surface modification technology, based on ceramic conversion treatment (CCT) in an oxidising medium between the glass transition temperature and the crystallisation temperature, has been developed to convert the surface of commercially available Zr44Ti11Cu10Ni11Be25 (Vitreloy 1b) BMG into ceramic layers. The engineered surfaces were fully characterised by in-situ X-ray diffraction, glow-discharge optical emission spectroscopy, scanning electron microscopy, transmission electron microscopy, and scanning transmission electron microscopy. The mechanical, chemical, and tribological properties were evaluated respectively by nano-indentation, electrochemical corrosion testing, tribological testing and the potential biocompatibility assessed by a cell proliferation assay. The results have demonstrated that after CCT at 350 °C for 40 h and at 380 °C for 4.5 h the original surfaces were converted into to a uniform 35–55-nm-thick oxide layer (with significantly reduced Ni and Cu concentration) followed by a 200–400-nm-thick oxygen-diffusion hardened case. The surface nano hardness was increased from 7.75 ± 0.36 to 18.32 ± 0.21 GPa, the coefficient of friction reduced from 0.5–0.6 to 0.1–0.2 and the wear resistance improved by more than 60 times. After 24 h of contact, SAOS-2 human osteoblast-like cells had increased surface coverage from 18% for the untreated surface to 46% and 54% for the 350 °C/40 h and 380 °C/4.5 h treated surfaces, respectively. The significantly improved tribological properties and biocompatibility have shown the potential of the ceramic conversion treated Zr-BMG for orthopaedic applications.

Are low-dose CT scans a satisfactory substitute for stereoradiographs for migration studies? A preclinical test of low-dose CT scanning protocols and their application in a pilot patient.

BACKGROUND: Computed tomography (CT) has the potential to acquire the data needed for migration studies of orthopedic joint implants of patients who have had tantalum beads implanted at the time of ...

Assessment of Embedded Conjugated Polymer Sensor Arrays for Potential Load Transmission Measurement in Orthopaedic Implants.

Load transfer through orthopaedic joint implants is poorly understood. The longer-term outcomes of these implants are just starting to be studied, making it imperative to monitor contact loads across the entire joint implant interface to elucidate the force transmission and distribution mechanisms exhibited by these implants in service. This study proposes and demonstrates the design, implementation, and characterization of a 3D-printed smart polymer sensor array using conductive polyaniline (PANI) structures embedded within a polymeric parent phase. The piezoresistive characteristics of PANI were investigated to characterize the sensing behaviour inherent to these embedded pressure sensor arrays, including the experimental determination of the stable response of PANI to continuous loading, stability throughout the course of loading and unloading cycles, and finally sensor repeatability and linearity in response to incremental loading cycles. This specially developed multi-material additive manufacturing process for PANI is shown be an attractive approach for the fabrication of implant components having embedded smart-polymer sensors, which could ultimately be employed for the measurement and analysis of joint loads in orthopaedic implants for in vitro testing.

Management of Infected Orthopedic Joint Implants: Pertinent Information for Family Medicine Physicians

Periprosthetic joint infections (PJIs) are one of the most devastating complications after total joint replacement. An early diagnosis can improve the outcome of treating PJI, and the first steps for diagnosing PJI are often conducted by a family doctor or a general practitioner. When a patient presents with a suspicion for PJI, the steps that must be followed are based on the clinical practice guideline by the American Academy of Orthopedic Surgeons (AAOS). Clinical symptoms, such as pain, are the main complaint that alerts physicians to a potential PJI, along with other symptoms such as erythema, warmth and tenderness around the surgical wound. These patients should receive x-rays of the affected joint, and laboratory tests such as erythrocyte sedimentation rate and C-reactive protein should be drawn. Physicians should actively avoid starting antibiotic therapy, obtaining nuclear medicine imaging, sending patients to infectious disease, or prescribing physical therapy. Finally, patients with a suspicion for PJI must be referred to an orthopedic surgeon who can establish the final diagnosis and conduct appropriate treatment.

Vitiligo and Allergic Complications from Orthopaedic Joint Implants: The Role of Benzoyl Peroxide

Orthopaedic joint implants and osteosynthetic materials are progressively being employed more often. Complications mainly include physical-mechanical problems and infections. Uncommonly, allergic reactions to an alloy metal or a bone cement component have been implicated. Less attention has been paid to the components of bone cement, such as acrylate, catalysers (e.g. peroxide), additive polymers or stabilisers. An important bone cement component is benzoylperoxide (BPO), an initiator of the process enhancement of the bone cement. Vitiligo is an acquired, progressive depigmenting disorder that can induce autoimmune diseases. The occurrence of vitiligo in combination with an infection or allergy is not well described, and this manuscript highlights the possibility of an occurrence of a vitiligo whenever the immunesystem is activated and T-cell activation is observed. The aim of this article was to analyze the diagnosis and management of vitiligo and allergic complications from orthopaedic joint implants due to benzoyl-peroxide and relevant patents.

Development of a protocol for the performance evaluation of wear machines used in tests of joint prostheses

The growing demand for orthopaedic joint implants and the large number of premature failure rates entails an increase in the number of surgeries; as a consequence, the costs of public and private health systems raise proportionally. The decrease of implants longevity is due to premature wear. Human gait simulation tests and orbital machines have contributed in the prediction of hip and knee joint implants performance. Wear tests in hip prostheses are standardized according to ISO 14242-1 and 14242-3. Lack of consensus on a universal standard for testing machines generates conflicting results and prevents a comparison of wear rates for prostheses evaluated by distinct mechanisms. This paper presents a protocol that was used to verify the performance and compliance of a hip simulation mechanical device designed to mimic the different standards. Tests performed with the above-mentioned apparatus are universal, for the simulator is capable of reproducing actual gait. Thus, commercially available wear testing machines ought to be certified for performance and standard compliance prior to be used as tools for obtaining actual rates of wear in joint prostheses.

Leitungswasseriontophorese

Since 1968, tap water iontophoresis has been employed as the method of choice for treating palmoplantar hyperhidrosis. Special electrodes also allow treatment of axillary hyperhidrosis. Tap water iontophoresis also can extend symptom -free intervals in dyshidrotic palmar eczema. The mechanism action is most likely a functional disturbance of the secretory mechanism of eccrine acini. During the induction phase, treatments are carried out once daily. Current direction may be switched before each treatment or, even better, kept constant until one side, preferably the dominant hand on the anode, is sweating normally. Then polarity is switched until both hands are adequately treated. During the weekly maintenance therapy, current direction is switched before each treatment. The most comfortable means of iontophoretic treatment employs pulsed direct current of high frequency (5-10kHz) which is better tolerated than continuous direct current and also suitable for children. Side effects are minimal and transient. Only slight skin irritation or sensations of discomfort may occur during treatment. Electric burns and shocks can be avoided by following routine precautions. Contraindications for tap water iontophoresis are metallic implants, such as cardiac pacemakers, or orthopaedic joint or bone implants, if they are within the electric circuit. Defects in the skin barrier, which can not be protected by petrolatum or insulating tape, also represent a temporary contraindication. Treatment in pregnancy is contraindicated, since experience is lacking.

In vitro studies on the effect of particle size on macrophage responses to nanodiamond wear debris

Nanostructured diamond coatings improve the smoothness and wear characteristics of the metallic component of total hip replacements and increase the longevity of these implants, but the effect of nanodiamond wear debris on macrophages needs to be determined to estimate the long-term inflammatory effects of wear debris. The objective was to investigate the effect of the size of synthetic nanodiamond particles on macrophage proliferation (BrdU incorporation), apoptosis (Annexin-V flow cytometry), metabolic activity (WST-1 assay) and inflammatory cytokine production (qPCR). RAW 264.7 macrophages were exposed to varying sizes (6, 60, 100, 250 and 500nm) and concentrations (0, 10, 50, 100 and 200μgml−1) of synthetic nanodiamonds. We observed that cell proliferation but not metabolic activity was decreased with nanoparticle sizes of 6–100nm at lower concentrations (50μgml−1), and both cell proliferation and metabolic activity were significantly reduced with nanodiamond concentrations of 200μgml−1. Flow cytometry indicated a significant reduction in cell viability due to necrosis irrespective of particle size. Nanodiamond exposure significantly reduced gene expression of tumor necrosis factor-α, interleukin-1β, chemokine Ccl2 and platelet-derived growth factor compared to serum-only controls or titanium oxide (anatase 8nm) nanoparticles, with variable effects on chemokine Cxcl2 and vascular endothelial growth factor. In general, our study demonstrates a size and concentration dependence of macrophage responses in vitro to nanodiamond particles as possible wear debris from diamond-coated orthopedic joint implants.

Allergic complications from orthopaedic joint implants: the role of delayed hypersensitivity to benzoyl peroxide in bone cement

Allergic complications from orthopaedic joint implants: the role of delayed hypersensitivity to benzoyl peroxide in bone cement

Allergic complications from orthopaedic joint implants: the role of delayed hypersensitivity to benzoyl peroxide in bone cement

Orthopaedic implants and osteosynthesis materials are increasingly being used. Complications include mainly physical-mechanical problems and infections. Uncommonly, an allergic reaction towards an alloy metal or a bone cement component has been implicated. Potential bone cement allergens include acrylates, benzoyl peroxide, N,N-dimethyl-p-toluidine, and gentamicin. Typical symptoms are pain, swelling, inflammatory skin reactions, implant loosening, and fistula formation. To report on 5 patients with complications from a knee or a shoulder joint implant in whom a relevant sensitization to benzoyl peroxide was shown. Patch tests were performed with the European baseline series, an extended metal series, and a bone cement series. Patch tests with benzoyl peroxide were performed twice in all patients. A bone cement-free replacement was chosen in sensitized patients. In 4 patients sensitized to benzoyl peroxide, a bone cement-free replacement resulted in a considerable decrease or disappearance of pain and swelling, and complete clearing of cutaneous symptoms. Components of bone cement, such as benzoyl peroxide, may rarely cause allergic complications. However, because of the irritant potential of these substances, careful performance, reading and interpretation of the patch tests is required.

A comparative study of titanium nitrides, TiN, TiNbN and TiCN, as coatings for biomedical applications

A strategy used to reduce wear of the ultra high molecular weight polyethylene (UHMWPE) component of orthopedic joint implants has been to coat the metallic part with a hard ceramic layer. The advantage of this procedure is to reduce both wear and ion release of the metal while keeping a high mechanical resistance. In the present study, the performance of three titanium nitride coatings: TiN, TiNbN, and TiCN for biomedical applications was assessed in terms of their surface properties and cytotoxicity. The morphology, chemical composition, and wettability were determined through atomic force microscopy (AFM) imaging, X-ray photoelectron spectroscopy (XPS) and contact angle measurement, respectively. The tribological behaviour of the coatings rubbing against UHMWPE in lubricated conditions was investigated using a pin-on-disk apparatus. Albumin adsorption on the three coatings was studied with a quartz crystal microbalance with dissipation (QCM-D) and AFM scratching. Cytotoxicity was determined both in direct or indirect contact of the cells with the coating materials. The results demonstrate that the three coatings have similar surface properties and are not cytotoxic. TiNbN seems to have the best tribological performance in the presence of albumin, although albumin adsorption is slightly higher on TiN.

Protein Adsorption Property of a Biomimetic Apatite Coating

Hydroxyapatite (HA) coating applied on metallic orthopedic joint implants can improve bone apposition, presumably through selective protein adsorption from blood plasma. However, the detailed interaction mechanism of HA coating with serum proteins remains to be largely elucidated. Protein adsorption behavior of a biomimetic apatite (BAp) coating in bovine calf serum and alpha calf fraction was investigated in this study. Plasma sprayed HA (PSHA) coating was tested in alpha calf fraction. The microstructure and composition of the coatings before and after serum incubation were characterized and the proteins adsorbed during the incubation were extracted from the coatings and analyzed. Microstructural transformation of the BAp coating accompanied by selective serum protein adsorption was observed after incubation in both media. The total protein amount adsorbed by the BAp coating in alpha calf faction was about three times that of the PSHA coating. To test the potential use of BAp coating as a carrier of therapeutic agents, interaction between the BAp coating and transforming growth factor (TGF)-β1 was studied. The growth factor was successfully loaded onto the coating in a sodium acetate buffer. Because of its high affinity to the coating, TGF-β1 could not be easily eluted in a bovine serum albumin containing solution but could be recovered after coating dissolution in acid. The strong protein adsorption property of the BAp coating was found to be due mainly to its unique nanoporous structure. The BAp coating can serve as an ideal carrier of therapeutic agents for aiding in the healing of bone and soft tissues.

Factors regulating osteoclast formation in human tissues adjacent to peri-implant bone loss: expression of receptor activator NFκB, RANK ligand and osteoprotegerin

Aseptic bone loss adjacent to orthopedic joint implants is a common cause of joint implant failure in humans. This study investigates the expression of key regulators of osteoclast formation, receptor activator NFκB (RANK), Receptor activator of NFκB ligand (RANKL) and osteoprotegerin (OPG), in the peri-implant tissues of patients with osteolysis compared with levels in synovial tissues from osteoarthritic and healthy subjects. Immunohistochemical studies demonstrated that significantly higher levels of RANKL protein ( p<0.05) were found in the peri-implant tissues of patients with implant failure than in similar tissues from osteoarthritic and healthy subjects. In contrast, OPG protein levels were similar in all tissues. RANKL, expressed as mRNA and protein, was predominantly associated with cells containing wear particles. Dual labeling studies showed that the cells expressing RANKL protein were macrophages. In situ hybridization studies confirmed that mRNA encoding for these proteins is also expressed by cells in the peri-implant tissues. In addition, RANK mRNA was expressed in cells that contained wear particles. These findings show that abnormally high levels of RANKL are expressed in peri-implant tissues of patients with prosthetic loosening and that these abnormal levels of RANKL may significantly contribute to aseptic implant loosening.

Detection of biomaterial-associated infections in orthopaedic joint implants.

Biomaterial-associated infection of orthopaedic joint replacements is the second most common cause of implant failure. Yet, the microbiologic detection rate of infection is relatively low, probably because routine hospital cultures are made only of swabs or small pieces of excised tissue and not of the surfaces of potentially infected implants. Joint replacements from patients in whom infection was suspected, after clinical, radiologic, and biochemical examinations, were used in this study. The aim of the current study was to compare the detection rate of infection in total joint replacements based on cultures of the excised tissue and scrapings from the biomaterial surface. Joint prostheses were retrieved from 22 patients requiring orthopaedic revision surgery because of suspected infection of their prostheses. Routine hospital culturing of tissue only showed bacterial growth in nine patients (41%). However, after prolonged culturing, bacterial growth was observed in 14 patients (64%), whereas extensive culturing of scrapings from the biomaterial surface indicated bacterial growth in 19 of the 22 patients (86%). In addition, confocal laser scanning microscopy enabled observation of biofilm bacteria on the surfaces of the explanted prostheses. Diagnosis in orthopaedic revision surgery should consider using a microbial or microscopic analysis of the surface of an explanted prosthesis, where the biofilm mode of growth firmly anchors and protects the infecting organisms. Improved detection of infection by analysis of the implant surface is expected to yield ameliorated therapy and a reduced need for revision surgery.

Cellular proliferation and cytokine responses of murine macrophage cell line J774A.1 to polymethylmethacrylate and cobalt-chrome alloy particles.

Wear debris from orthopedic joint implants have been postulated to initiate a cascade of complex cellular events that results in aseptic loosening of the prosthesis and eventually in loss of function of the device. The impact of biomaterials used in these devices on host inflammatory response has not been examined extensively. Polymethylmethacrylate (PMMA) and cobalt-chrome alloy (CoCr) are biomaterials widely used in orthopedic implant devices. Macrophages are an important component of the host inflammatory response, and we have examined the effect of PMMA and CoCr particles on the murine macrophage cell line J774A.1. Our objective was to obtain a comprehensive analysis of the particle-macrophage interaction, and we examined a number of basic biological responses of the J774A.1 cell line, including cell proliferation, apoptosis, cytokines secreted into the culture supernatant (TNFalpha, IL-1alpha, IL-6, and IL-12) and mRNA expression of the cytokines (TNFalpha, IL-1alpha, IL-6, IFN-alpha, M-CSF, and TGF-beta) in response to PMMA and CoCr particles. Our results indicate that the relative contribution of PMMA and CoCr particles in J774A.1 activation is negligible, and we observed a change in metabolic activity of J774A.1 cells only at higher concentrations of CoCr particles.

Cellular proliferation and cytokine responses of murine macrophage cell line J774A.1 to polymethylmethacrylate and cobalt–chrome alloy particles

Wear debris from orthopedic joint implants have been postulated to initiate a cascade of complex cellular events that results in aseptic loosening of the prosthesis and eventually in loss of function of the device. The impact of biomaterials used in these devices on host inflammatory response has not been examined extensively. Polymethylmethacrylate (PMMA) and cobalt–chrome alloy (CoCr) are biomaterials widely used in orthopedic implant devices. Macrophages are an important component of the host inflammatory response, and we have examined the effect of PMMA and CoCr particles on the murine macrophage cell line J774A.1. Our objective was to obtain a comprehensive analysis of the particle–macrophage interaction, and we examined a number of basic biological responses of the J774A.1 cell line, including cell proliferation, apoptosis, cytokines secreted into the culture supernatant (TNFα, IL-1α, IL-6, and IL-12) and mRNA expression of the cytokines (TNFα, IL-1α, IL-6, IFN-α, M-CSF, and TGF-β) in response to PMMA and CoCr particles. Our results indicate that the relative contribution of PMMA and CoCr particles in J774A.1 activation is negligible, and we observed a change in metabolic activity of J774A.1 cells only at higher concentrations of CoCr particles. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 655–663, 1998.

Macrophage Activation Results in Bone Resorption

Monocytes or macrophages from important accessory cells in the regulation of bone metabolism and destruction. Cells of the mononuclear phagocyte lineage form the precursor cells of the osteoclasts. Soluble products produced by activated macrophages regulate progenitor cell proliferation, recruitment, differentiation, and activity of osteoblasts and osteoclasts. After osteoclasts are removed from the resorption site, macrophages process bone surfaces and create a cement line before osteoblasts enter to form new bone. Although osteolysis associated with normal bone remodeling is seen as an osteoclast driven process, it may be that in chronic inflammation macrophage activation and vascular derangements lead to low pH, local bone demineralization (acid attack), and H+ mediated stimulation of the primary afferent nociceptive nerve fibers (bone pain). Osteoclasts are not able to attach to demineralized bone or to osteoid surfaces. However, if macrophages degrade the demineralized organic bone matrix, chemotactic factors and attachment sites for osteoclasts are produced. In such a scenario, the osteoclast-osteoblast mediated activation, resorption, and formation cycle would be secondarily activated. Such events may play a role in the most common orthopaedic problem related to macrophage activation, aseptic loosening of orthopaedic joint implants, which is secondary to a chronic foreign body reaction and to micromovement.

Production of cytokines around loosened cemented acetabular components. Analysis with immunohistochemical techniques and in situ hybridization.

The chronic inflammatory response to wear particles from orthopaedic joint implants is believed to cause osteolysis and to contribute to prosthetic loosening. Previous in vitro experiments have demonstrated that particulate debris from joint implants causes cells in culture to release products that have been implicated in this pathological bone resorption. The purpose of the current study was to investigate the in vivo features of this complex process in patients who had had a total hip replacement. Membraneous tissue was obtained from the cement-bone interface of ten polyethylene acetabular components that had been revised for aseptic loosening in ten patients. The immunoperoxidase technique, which involves the use of specific antibodies for each cell type, showed that macrophages were the predominant cellular constituents but also that fibroblasts, many of which were not identified on plain histological study, were present and were actively producing collagen. T lymphocytes were present variably, but they generally composed less than 10 percent of the cells. Particulate debris (polyethylene, methylmethacrylate, and metal) was present in all membrane specimens but was intracellular only in macrophages and multinucleated giant cells. 35S-labeled nucleic-acid probes, complementary to human interleukin-1-beta and to platelet-derived growth-factor-2 messenger RNA (mRNA), were hybridized with serial tissue sections. Hybridization demonstrated interleukin-1-beta mRNA predominantly in macrophages, and not in fibroblasts or in T lymphocytes to any major extent. In contrast, immunolocalization demonstrated interleukin-1-beta protein on both macrophages and fibroblasts, suggesting that macrophages release interleukin-1-beta, which then binds to both fibroblasts and macrophages. Platelet-derived growth-factor transcripts were found in both macrophages and fibroblasts.

Key references in biomaterials: bone/biomaterial interface in orthopedic joint implants.

Key references in biomaterials: bone/biomaterial interface in orthopedic joint implants.