Failure Of Total Joint Replacement Research Articles

Zucker Diabetic-Sprague Dawley Rats Have Impaired Peri-Implant Bone Formation, Matrix Composition, and Implant Fixation Strength.

An increasing number of patients with type 2 diabetes (T2DM) will require total joint replacement (TJR) in the next decade. T2DM patients are at increased risk for TJR failure, but the mechanisms are not well understood. The current study used the Zucker Diabetic-Sprague Dawley (ZDSD) rat model of T2DM with Sprague Dawley (SPD) controls to investigate the effects of intramedullary implant placement on osseointegration, peri-implant bone structure and matrix composition, and fixation strength at 2 and 10 weeks post-implant placement. Postoperative inflammation was assessed with circulating MCP-1 and IL-10 2 days post-implant placement. In addition to comparing the two groups, stepwise linear regression modeling was performed to determine the relative contribution of glucose, cytokines, bone formation, bone structure, and bone matrix composition on osseointegration and implant fixation strength. ZDSD rats had decreased peri-implant bone formation and reduced trabecular bone volume per total volume compared with SPD controls. The osseointegrated bone matrix of ZDSD rats had decreased mineral-to-matrix and increased crystallinity compared with SPD controls. Osseointegrated bone volume per total volume was not different between the groups, whereas implant fixation was significantly decreased in ZDSD at 2 weeks but not at 10 weeks. A combination of trabecular mineral apposition rate and postoperative MCP-1 levels explained 55.6% of the variance in osseointegration, whereas cortical thickness, osseointegration mineral apposition rate, and matrix compositional parameters explained 69.2% of the variance in implant fixation strength. The results support the growing recognition that both peri-implant structure and matrix composition affect implant fixation and suggest that postoperative inflammation may contribute to poor outcomes after TJR surgeries in T2DM patients. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Insights into Oxidation of the Ultrahigh Molecular Weight Polyethylene Artificial Joint Related to Lipid Peroxidation.

Oxidative degradation of ultrahigh molecular weight polyethylene (UHMWPE) bearings is one of the main factors that deteriorates their mechanical properties and abrasive wear resistance, which further results in the failure of total joint replacements. Absorption and diffusion of synovial fluids have been considered as causes of the oxidation of UHMWPE bearings. However, the role of synovial fluids in oxidation of UHMWPE remains elusive. In this work, we aimed to reveal the oxidation mechanism of UHMWPE joints with respect to squalene (a representative component of the synovial fluid). The UHMWPE doped in squalene showed slight oxidation, while severe oxidation was observed when squalene doped UHMWPE was exposed to oxygen atmosphere. Squalene manifested lipid peroxidation with notable oxidation products and oxygen-derived free radicals during thermo-oxidative aging. Lipid peroxidation was deduced to follow two routes including autoxidation and thermal oxidation. The aggressive free radicals of squalene abstracted hydrogen atoms from the UHMWPE chains, initiating the oxidation of UHMWPE artificial joints. These findings not only provide evidence for comprehending the process of squalene-induced UHMWPE oxidation but also are instructive to develop highly oxidative-resistant UHMWPE.

When Has a Knee or Hip Replacement Failed? A Patient Perspective.

To define the patient perspective of what constitutes a failure of total joint replacement (TJR) in a qualitative study. We used the nominal group technique (NGT) with participants who had undergone elective total hip replacements (THR) and/or total knee replacements (TKR) to answer the question, "When would you consider a knee or hip replacement to be a failure?" We performed 8 nominal groups with 42 participants, all of whom had undergone THR and/or TKR between 2016 and 2018. Of these, 48% were male, 17% were Black, 79% had college education or above, and 76% had had osteoarthritis as the underlying diagnosis. The nominated responses/themes that were ranked the highest by the participants were as follows: (1) refractory index joint pain (80 votes); (2) occurrence of postoperative adverse events (54 votes); (3) unable to resume normal activities or go back to work (38 votes); (4) little or no improvement in quality of life (35 votes); (5) early revision surgery (35 votes); (6) death (7 votes); and (7) other, including nurse or physician negligence (2 votes) and expectation-outcome mismatch (1 vote). Lack of relief of pain or restoration of function or quality of life, or the occurrence of surgical complications after TJR were defined as TJR failure by participants. Functional TJR failure seems as important or more important than surgical failure. This patient perspective emphasizing pain, function, satisfaction, adverse events, and revision as critical domain components of TJR failure independently validated their inclusion in the TJR core domain set for clinical trials in people undergoing knee or hip TJR.

Regulation of Extracellular Matrix Remodeling Proteins by Osteoblasts in Titanium Nanoparticle-Induced Aseptic Loosening Model.

Titanium (Ti)-wear particles, formed at the bone-implant interface, are responsible for aseptic loosening, which is a main cause of total joint replacement failure. There have been many studies on Ti particle-induced function changes in mono-cultured osteoblasts and synovial cells. However, little is known on extracellular matrix remodeling displayed by osteoblasts when in coexistence with Synovial cells. To further mimic the bone-implant interface environment, we firstly established a nanoscaled-Ti particle-induced aseptic loosening system by co-culturing osteoblasts and Synovial cells. We then explored the impact of the Synovial cells on Ti particle-engulfed osteoblasts in the mimicked flamed niche. The matrix metalloproteinases and lysyl oxidases expression levels, two protein families which are critical in osseointegration, were examined under induction by tumor necrosis factor-alpha. It was found that the co-culture between the osteoblasts and Synovial cells markedly increased the migration and proliferation of the osteoblasts, even in the Ti-particle engulfed osteoblasts. Importantly, the Ti-particle engulfed osteoblasts, induced by TNF-alpha after the co-culture, enhanced the release of the matrix metalloproteinases and reduced the expressions of lysyl oxidases. The regulation of extracellular matrix remodeling at the protein level was further assessed by investigations on gene expression of the matrix metalloproteinases and lysyl oxidases, which also suggested that the regulation started at the genetic level. Our research work has therefore revealed the critical role of multi cell-type interactions in the extracellular matrix remodeling within the peri-prosthetic tissues, which provides new insights on aseptic loosening and brings new clues about incomplete osseointegration between the implantation materials and their surrounding bones.

Robotic joint replacement surgery: does technology improve outcomes?

Osteoarthritis is a common disease that leads patients to seek total joint replacement (TJR). Component misalignment leads to failure of TJR. Computer navigation enhances the precision of component alignment, but the addition of robotic guidance can boost TJR to a higher level of accuracy. Some 29 English-language peer-reviewed articles from 2002 to 2013 and 1 Web site were reviewed. A conceptual framework was adapted to explain benefits and barriers of adoption of robotic TJR. A total of 10 studies were reviewed with focus on more precise alignment, outcomes, length of stay, and costs. Cost to obtain robotic surgical equipment was found to be about $1 million with maintenance costs approaching $350 000. Robotic techniques compared with conventional orthopedic surgery showed slight variances in favor of robotic procedures. Although hospitals have the potential to reduce costs and improve outcomes with robotic TJR, the expenditure and maintenance have not been proven a clear return on investment. As surgical robotic technology evolves in accuracy and accessibility, joint replacement surgery may benefit from improved precision and decreased health care costs. However, equipment purchase and upkeep costs and surgeon training may impede use to its full potential in orthopedic surgery in the United States.

Role of Surface Industrial Finishing Process of Joint Implant UHMWPE on their Tribological Behaviour

Joint implants have as bearing couples metal on metal, ceramic on metal and metal on polyethylene. The most widely used bearing couple for artificial joint systems is the combination of a polyethylene (PE) acetabular liner and a cobalt–chromium (Co–Cr) alloy femoral head. Although highly used, it is known that wearing of the polyethylene part of total joint implants is the primary cause of premature failure of total joint replacements [1]. Polyethylene particles tend to migrate into the joint creating inflammation, ostelysis and, in the end the loss of the implant. Industrials use different method for the surface finishing process of the polyethylene part of joint implants that lead to different types of surface morphologies. In this study, using atomic force microscopy technique and tribological methods, we have investigated the influence of polyethylene surface morphology on mechanical properties, degradation and friction. Results have shown that polyethylene surfaces obtained by high speed turning machine lead to low friction coefficient and less degradation of the surface during friction test.

Failure of total hip implants: metals and metal release in 52 cases.

The pathogenesis of total joint replacement failure is multifactorial. One hypothesis suggests that corrosion and wear of alloys result in metal ion release, which may then cause sensitization and even implant failure, owing to the acquired immune reactivity. To assess cobalt, nickel and chromium(VI) release from, and the metal composition of, failed metal-on-ethylene total hip replacements. Implant components from 52 revision cases were evaluated with spot tests for free nickel, cobalt, and chromium (VI) ions. Implant composition was determined with X-ray fluorescence spectroscopy, and information on the reason for revision and complications in relation to surgery was collected from the medical charts when possible (72%). For 10 implants, corrosion was further characterized with scanning electron microscopy. We detected cobalt release from three of 38 removed femoral heads and from one of 24 femoral stems. Nickel release was detected from one of 24 femoral stems. No chromium(VI) release was detected. We found that cobalt and nickel were released from some failed total hip arthroplasties, and corrosion was frequently observed. Metal ions and particles corroded from metal-on-polyethylene may play a role in the complex aetiopathology of implant failure.

Titanium particles up-regulate the activity of matrix metalloproteinase-2 in human synovial cells

Wear debris particle-induced osteolysis and subsequent aseptic loosening is one of the major causes of failure of total joint replacement. The purpose of this study was to investigate the effect of titanium implant material and inflammatory cytokines on human synovial cells and the development to osteolysis and aseptic loosening. This study investigated the effect of titanium implant material on the ECM-degraded MMP-2 in human synovial cells and analyzed the contribution of synovial cells in osteolysis and aseptic loosening. When human synovial cells are exposed to titanium materials, MMP-2 activity is induced by 1.72 ± 0.14-fold with Ti disc and 3.95 ± 0.10-fold with Ti particles, compared with that of the controls, respectively. Inflammatory cytokines TNFα and IL-1β are also shown to induce MMP-2 activity by 3.65 ± 0.28-fold and 6.76 ± 0.28-fold, respectively. A combination of Ti particles and cytokines induces MMP-2 activities to a higher level (10.54 ± 0.45-fold). Inhibitors of various signal pathways involved in MMP-2 reverse Ti particle-induced MMP-2 activities. Synovial cells surrounding the bone-prosthesis interface may contribute to production of MMP-2, and NFκB inhibitors may be explored as potential therapeutics to alleviate wear debris-induced osteolysis and aseptic loosening.

Toll‐like receptors‐2 and 4 are overexpressed in an experimental model of particle‐induced osteolysis

Aseptic loosening secondary to particle-associated periprosthetic osteolysis remains a major cause of failure of total joint replacements (TJR) in the mid- and long term. As sentinels of the innate immune system, macrophages are central to the recognition and initiation of the inflammatory cascade, which results in the activation of bone resorbing osteoclasts. Toll-like receptors (TLRs) are involved in the recognition of pathogen-associated molecular patterns and danger-associated molecular patterns. Experimentally, polymethylmethacrylate and polyethylene (PE) particles have been shown to activate macrophages via the TLR pathway. The specific TLRs involved in PE particle-induced osteolysis remain largely unknown. We hypothesized that TLR-2, -4, and -9 mediated responses play a critical role in the development of PE wear particle-induced osteolysis in the murine calvarium model. To test this hypothesis, we first demonstrated that PE particles caused observable osteolysis, visible by microCT and bone histomorphometry when the particles were applied to the calvarium of C57BL/6 mice. The number of TRAP positive osteoclasts was significantly greater in the PE-treated group when compared to the control group without particles. Finally, using immunohistochemistry, TLR-2 and TLR-4 were highly expressed in PE particle-induced osteolytic lesions, whereas TLR-9 was downregulated. TLR-2 and -4 may represent novel therapeutic targets for prevention of wear particle-induced osteolysis and accompanying TJR failure.

Mutant MCP-1 protein delivery from layer-by-layer coatings on orthopedic implants to modulate inflammatory response

Total joint replacement (TJR) is a common and effective surgical procedure for hip or knee joint reconstruction. However, the production of wear particles is inevitable for all TJRs, which activates macrophages and initiates an inflammatory cascade often resulting in bone loss, prosthetic loosening and eventual TJR failure. Macrophage Chemoattractant Protein-1 (MCP-1) is one of the most potent cytokines responsible for macrophage cell recruitment, and previous studies suggest that mutant MCP-1 proteins such as 7ND may be used as a decoy drug to block the receptor and reduce inflammatory cell recruitment. Here we report the development of a biodegradable, layer-by-layer (LBL) coating platform that allows efficient loading and controlled release of 7ND proteins from the surface of orthopedic implants using as few as 14 layers. Scanning electron microscopy and fluorescence imaging confirmed effective coating using the LBL procedure on titanium rods. 7ND protein loading concentration and release kinetics can be modulated by varying the polyelectrolytes of choice, the polymer chemistry, the pH of the polyelectrolyte solution, and the degradation rate of the LBL assembly. The released 7ND from LBL coating retained its bioactivity and effectively reduced macrophage migration towards MCP-1. Finally, the LBL coating remained intact following a femoral rod implantation procedure as determined by immunostaining of the 7ND coating. The LBL platform reported herein may be applied for in situ controlled release of 7ND protein from orthopedic implants, to reduce wear particle-induced inflammatory responses in an effort to prolong the lifetime of implants.

A study on wear behavior of γ-UHMWPE sliding against 316L stainless steel counter face

The main cause of long term failure of total joint replacements is due to generation of wear particles in ultrahigh molecular weight polyethylene (UHMWPE). In this study UHMWPE specimens were prepared in injection molding machine by varying the melt temperature. Then they were irradiated and subjected to wear tests in a hip joint simulator. The tests were conducted by varying the contact loads where the specimens were slid against 316L stainless steel and UHMWPE counter faces. The study revealed that the specimens sliding against stainless steel counter face have better wear resistance than when sliding against UHMWPE counter face.

Radiostereometric analysis of early implant migration – a valuable tool to ensure proper introduction of new implants

Radiostereometric analysis of early implant migration – a valuable tool to ensure proper introduction of new implants

Management of infection after total knee arthroplasty

Infection after total knee arthroplasty (TKA) remains one of the most dreaded and difficult complications to treat. Infection remains one of the most common reasons for failure of total joint replacement. Several options are available for treatment, including antibiotic suppression with retention of the prosthesis, irrigation and debridement with polyethylene exchange, single and two-stage exchange arthrodesis, amputation, and arthroplasty. This review examines the newest literature and recommendations regarding these various modes of management.

In Vivo Biological Response to Vitamin E and Vitamin-E-Doped Polyethylene

Cross-linking has decreased the wear of ultra-high molecular weight polyethylene, a cause of osteolysis leading to total joint replacement failure. Compared with melting or annealing, doping cross-linked ultra-high molecular weight polyethylene with vitamin E stabilizes free radicals from irradiation while maintaining mechanical properties and wear resistance. This study was done to determine the local tissue effects of free vitamin E and vitamin E eluted from ultra-high molecular weight polyethylene implants in the joint space. Three studies were performed. First, pure vitamin E and solubilized vitamin E were injected into rabbit knees to simulate vitamin-E elution from radiation cross-linked ultra-high molecular weight polyethylene; second, vitamin-E-doped, irradiated ultra-high molecular weight polyethylene plugs were implanted into dorsal subcutaneous pouches of rabbits to determine the local effects of vitamin-E elution from radiation cross-linked ultra-high molecular weight polyethylene; and, third, two groups of vitamin-E-doped, irradiated acetabular liners (high surface and uniform vitamin-E concentration profiles) were compared with undoped, control ultra-high molecular weight polyethylene liners in a canine model of total hip replacement to determine the effect of possible vitamin-E elution on bone ingrowth and the local tissue response to it in a load-bearing environment. Injection of solubilized vitamin E resulted in histologically normal surrounding soft tissue at both two and twelve-week follow-up intervals, while injection of pure vitamin E resulted in acute and chronic inflammation at the time of the two-week follow-up. Both control and vitamin-E-doped subcutaneous plugs showed inflammation associated with surgery at two weeks of follow-up, but showed stable fibrous encapsulation without inflammation at twelve weeks of follow-up. In the canine total hip replacement model, there was no qualitative difference in local tissue appearance and no significant difference in the percent bone ingrowth and the percent bone density between the control and vitamin-E groups. These investigations showed that vitamin-E-doped ultra-high molecular weight polyethylene plugs and total hip replacement components are well tolerated in both a small and a large-animal model with no observed adverse effects on the surrounding tissues at twelve weeks of follow-up.

Binding of proteins to ultra high molecular weight polyethylene wear particles as a possible mechanism of macrophage and lymphocyte activation

Binding of five human plasma proteins (IgG, serum albumin, α(1)-acid glycoprotein, holo-transferrin, α(1)-antitrypsin) to ultra high molecular weight polyethylene wear particles (0.1-10 μm) isolated from hip periprosthetic tissues was studied in vitro. All tested plasma proteins were bound to wear particles in a similar way indicating irreversible binding. Analogous interaction was found also between GUR 4120 particles (diameter ∼250 μm) and two tested plasma proteins (human serum albumin and α(1)-acid glycoprotein). The binding was not affected by pH of a buffer or the isoelectric point of bound proteins; thus it was apparently of clearly hydrophobic nature. We hypothesize that the binding causes some unfolding of the bound proteins, thus exposing new determinants with which sensitive cells may react. This could be a mechanism by which polyethylene wear particles trigger, for example, macrophages activity and thence initiate aseptic inflammation and cause the failure of total joint replacements. Results can contribute to the choice of a convenient construction type of prostheses.

Biotribological behavior of ultra high molecular weight polyethylene composites containing bovine bone hydroxyapatite

Abstract Wear particles of ultrahigh molecular weight polyethylene (UHMWPE) are the main cause of long-term failure of total joint replacements. Therefore, increasing its wear resistance or bioactivity will be very useful in order to obtain high quality artificial joints. In our study, UHMWPE composites filled with the bovine bone hydroxyapatite (BHA) were prepared by the method of compression moulding. A ball-on-disc wear test was carried out with a Universal Micro-Tribometer to investigate the friction and wear behavior of a Si3N4 ceramic ball, cross-sliding against the UHMWPE/BHA composites with human plasma lubrication. At the same time, the profiles of the worn grooves on the UHMWPE/BHA surface were scanned. The experimental results indicate that the addition of BHA to UHMWPE had a significant effect on the biotribological behavior of UHMWPE cross-sliding against the Si3N4 ceramic ball. The addition of BHA powder enhanced the hardness and modulus of elasticity of these composites and decreased the friction coefficients and wear rates under conditions of human plasma lubrication. When the added amount of BHA powders was up to 20%∼30%, UHMWPE/BHA composites demonstrated the designed performance of the mechanical properties and biotribological behavior.

Accelerated wear testing with a microfabricated surface to evaluate the lubrication ability of biomolecules on polyethylene

AbstractWear of ultrahigh‐molecular‐weight polyethylene (UHMWPE) and wear‐particle‐induced osteolysis and bone resorption are the major factors causing the failure of total joint replacements. It is feasible to improve the lubrication and reduce the wear of artificial joints. We need further understanding of the lubrication mechanism of the synovial fluid. The objective of this study is to evaluate the lubricating ability of three major components in the synovial fluid: albumin, globulin, and phospholipids. An accelerated wear testing procedure in which UHMWPE is rubbed against a microfabricated surface with controlled asperities has been developed to evaluate the lubrication behavior. An analysis of the wear particle dimensions and wear amount of the tests has provided insights for comparing their lubrication performance. It is concluded that the presence of biomolecules at the articulating interface may reduce friction. A higher concentration of a biological lubricant leads to a decrease in the wear particle width. In addition, in combination with the wear results and mechanical analysis, the roles of individual biomolecules contributing to friction and wear at the articulating interface are discussed. These results can help us to identify the role of the biomolecules in the boundary lubrication of artificial joints, and further development of lubricating additives for artificial joints may be feasible. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Effect of etidronate on COX-2 expression and PGE2 production in macrophage-like RAW 264.7 cells stimulated by titanium particles

BackgroundThe most common failure of total joint replacement is aseptic loosening in association with osteolysis. Previous reports have shown that prostaglandin E2 (PGE2) secreted from macrophages that phagocytosed wear debris induced periprosthetic osteolysis. Many clinical studies have reported that bisphosphonate therapy reduced periprosthetic bone loss and loosening of the implants after total joint replacements. Bisphosphonates are synthetic compounds with the ability to decrease bone resorption. In addition, some bisphosphonates have been reported to have anti-inflammatory effects by reducing the secretion of pro-inflammatory cytokines. However, the mechanism of bisphosphonates that reduces periprosthetic bone resorption remains unclear. The purpose of this study was to investigate one of the mechanisms by which etidronate (EHDP) inhibits periprosthetic bone resorption. MethodsMacrophage-like RAW 264.7 cells were treated with EHDP at concentrations of 0.001, 0.01, 0.1, 1, 10, and 100 μM together with the titanium particles at a concentration of 1 mg/ml. After a 24-h culture period, total mRNA was isolated and reverse transcription-polymerase chain reaction (RT-PCR) was done to examine the expression of cyclooxygenase-2 (COX-2). The supernatants were also collected and production of PGE2, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were quantified using an enzyme-linked immunosorbent assay (ELISA). ResultsAnalyses showed that COX-2 expression and PGE2 production were suppressed by EHDP in a dose-dependent manner. By 100 μM of EHDP, PGE2 production of the cells was suppressed approximately to the level of the nonstimulated cells. Production of IL-1β, IL-6, and TNF-α in the supernatant was also suppressed by EHDP. ConclusionsThe blockage effect of pro-inflammatory cytokines is a possible etidronate mechanism that reduces bone resorption around implants.

Polyethylene Particle-Induced Bone Resorption in Substance P-Deficient Mice

Aseptic loosening is the major cause of total joint replacement failure. Substance P (SP) is a neurotransmitter richly distributed in sensory nerve fibers, bone, and bone-related tissue. The purpose of this study was to investigate the potential impact of SP on bone metabolism in polyethylene particle-induced osteolysis. We utilized the murine calvarial osteolysis model based on ultrahigh molecular weight polyethylene (UHMWPE) particles in 14 wild-type mice (C57BL/J6) and 14 SP-deficient mice. Group 1 (C57BL/J 6) and group 3 (SP-knockout) received sham surgery, and group 2 (C57BL/J6) and group 4 (SP-knockout) were treated with polyethylene particles. Analytical methods included three-dimensional micro-computed tomographic (micro-CT) analysis and histomorphometry. Bone resorption was measured within the midline suture. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase-positive cells. UHMWPE-particle treated SP-deficient mice showed significantly reduced osteolysis compared to wild-type mice, as confirmed by histomorphometry (P < 0.001) and micro-CT (P = 0.035). Osteoclast numbers were significantly reduced in groups 3 and 4 compared to groups 1 and 2 (P < 0.001). Unexpectedly, SP-deficient mice (group 3) showed a significantly increased absolute bone mass compared to wild-type mice (group 1) (P = 0.02). The findings of our murine calvaria model lead to the assumption that SP is a promoter in particle-induced osteolysis. The pathophysiology of aseptic loosening is complex, and neuropeptides are not solely responsible for the progress of implant loosening; however, we conclude that there could be coherence between neurotransmitters and particle-induced osteolysis in patients with aseptic loosening.

Wear of crosslinked polyethylene under different tribological conditions

Ultra high molecular weight polyethylene (UHMWPE) wear debris has been shown to be a major cause of long term failure of total joint replacements. Recently, crosslinking has been extensively introduced to reduce the wear of UHMWPE. In this study the wear of non-crosslinked and crosslinked UHMWPE were compared under a range of conditions. The materials examined were UHMWPE GUR 1050, non-crosslinked, moderately crosslinked--5MRad, and highly crosslinked--10MRad. The wear was examined on a multidirectional pin on plate rig. The effect of counterface roughness on wear under different kinematics was examined. The results from the different counterface conditions showed that highly crosslinked UHMWPE had significantly lower wear against both smooth and scratched counterfaces. However the reduction in wear for crosslinked polyethylene was less for scratched counterfaces. The second part of the study showed that all the UHMWPE's produced lower wear rates under lower multidirectionality because of reduced cross shear frictional forces and work. These findings are relevant to the consideration of the use of crosslinked polyethylene in the knee, where the kinematics have lower levels of cross shear and in the hip and knee against roughened metallic counterfaces.