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Orhun K. Muratoglu - One of the best experts on this subject based on the ideXlab platform.

  • particles from vitamin e diffused hxl uhmwpe induce less osteolysis compared with virgin hxl uhmwpe in vivo
    Journal of Bone and Joint Surgery-british Volume, 2016
    Co-Authors: Orhun K. Muratoglu, David A Bichara, Erik Malchau, Nanna Hylleholt, Selami Cakmak
    Abstract:

    Introduction UHMWPE particle-induced osteolysis is one of the major causes of arthroplasty revisions. Recent in vitro findings have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased potential to cause osteolysis (Bladed C. L. et al, JBMR B 2012 and 2013). This is of significant importance since VE-stabilized cross-linked UHMWPEs were recently introduced for clinical use, and there is no in vivo data determining the effects of wear Debris. In this study we hypothesized that particles from VE-stabilized, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Methodology Study groups were the following: 1). Radiation cross-linked VE-UHMWPE (0.8% by weight) diffused after 100 kGy; 2). Radiation cross-linked virgin UHMWPE (virgin UHMWPE); 3). Sham controls. Particle generation and implantation: UHMWPE was sent to Bioengineering Solutions (Oak Park, IL) for particle generation. After IACUC approval, C57BL/6 mice ( n =12 for each group) received equal amount of Particulate Debris (3mg) overlying the calvarium and were euthanized after 10 days. Micro-CT scans: High resolution micro-CT scans were performed using a set voltage of 70 kV and current of 70 µA. Topographical Grading Scale: Each calvarial bone was blindly scored using the following scale: 0=No osteolysis, defined as intact bone; 1=Minimal osteolysis, affecting 1/3 or less of the bone area; 2=Moderate osteolysis, affecting at least 2/3 of the bone area; 3=Severe osteolysis, defined as completely osteolytic bone. Histology: H&E and TRAP staining was done on tissue to confirm micro-CT findings and quantify osteoclasts. Statistical Analysis: Inter-rater analysis was done using Cohen9s kappa analysis. An inter-rater coefficient >0.65 was considered as high inter-rater agreement. Comparison between groups was made using one-way ANOVA with post hoc Bonferroni correction for multiple comparisons. Correlations are reported as Spearman9s rho. P -value Results More than 83% of the VE-UHMWPE and more than 85% of the virgin UHMWPE particles measured less than 1 µm in mean particle size. There was a statistically significant greater level of osteolysis visualized on the topographical grading scale in calvaria implanted with virgin UHMWPE wear particles. Micro-CT findings were confirmed histologically (Fig. 1). A greater amount of inflammatory tissue overlaying the calvaria was observed in the virgin UHMWPE group when compared to both shams and VE-UHMWPE groups. Post hoc analysis revealed significant difference between VE-UHMWPE and virgin UHMWPE for the topographical osteolysis grading score ( p =0.002) but no difference in osteoclast counts ( p =0.293). Discussion and Conclusion This is the first in vivo study reporting the effects of clinically-relevant UHMWPE particles generated from a VE-UHMWPE implant that is in current clinical use. These results suggest that VE-UHMWPE particles have reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model. Arthroplasty procedures using VE-UHMWPE might be less susceptible to peri-prosthetic loosening caused by wear Debris.

  • vitamin e diffused highly cross linked uhmwpe particles induce less osteolysis compared to highly cross linked virgin uhmwpe particles in vivo
    Journal of Arthroplasty, 2014
    Co-Authors: David A Bichara, Erik Malchau, Selami Cakmak, Nanna H Sillesen, Petur G Nielsen, Orhun K. Muratoglu
    Abstract:

    Recent in vitro findings suggest that UHMWPE wear particles containing vitamin E (VE) may have reduced biologic activity and decreased osteolytic potential. We hypothesized that particles from VE-stabilized, radiation cross-linked UHMWPE would cause less osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Groups received equal amount of Particulate Debris overlaying the calvarium for 10 days. Calvarial bone was examined using high resolution micro-CT and histomorphometric analyses. There was a statistically significant difference between virgin (12.2%±8%) and VE-UHMWPE (3%±1.4%) groups in regards to bone resorption (P=0.005) and inflammatory fibrous tissue overlaying the calvaria (0.48 vs. 0.20, P<0.0001). These results suggest that VE-UHMWPE particles have reduced osteolytic potential in vivo when compared to virgin UHMWPE.

  • particles from vitamin e diffused highly cross linked uhmwpe induce less osteolysis compared with virgin uhmwpe in a murine calvarial bone model
    Journal of Bone and Joint Surgery-british Volume, 2014
    Co-Authors: David A Bichara, Erik Malchau, Selami Cakmak, Nanna H Sillesen, Orhun K. Muratoglu
    Abstract:

    Summary Statement Vitamin E-UHMWPE particles have a reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model. Introduction Ultra high-molecular weight polyethylene (UHMWPE) particle-induced osteolysis is one of the major causes of arthroplasty revisions. The lack of particle clearance from the joint inevitably leads to the upregulation of the inflammatory cascade, resulting in bone resorption and implant loosening. Recent in vitro findings (Bladed CL et al. ORS 2011 and J Biomed Mater Res B Appl Biomater, 2012) have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased potential to cause osteolysis. This is of significant importance since VE-stabilised cross-linked UHMWPEs were recently introduced for clinical use, and there is no in vivo data determining the effects of wear Debris from this new generation of implants. In this study we hypothesised that particles from VE-stabilised, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Methods Study groups were the following: 1) Radiation cross-linked VE-UHMWPE, approximately 0.8% by weight, diffused after 100 kGy; 2). Radiation cross-linked virgin UHMWPE (virgin UHMWPE); 3). Shams. Particle generation and implantation: UHMWPE was sent to Bioengineering Solutions (Oak Park, IL) for particle generation. After IACUC approval, C57BL/6 mice ( n =12 for each group) received equal amount of Particulate Debris (3mg) overlying the calvarium and were euthanised after 10 days. Micro-CT scans: High resolution micro-CT scans were performed using an X-Tek HMX ST 225 with a set voltage of 70 kV and current of 70 µA. Topographical Grading Scale: Each calvarial bone (interparietal, right and left parietal, right and left frontal) was blindly scored using the following scale: 0=No osteolysis, defined as intact bone; 1=Minimal osteolysis, affecting 1/3 or less of the bone area; 2=Moderate osteolysis, affecting at least 2/3 of the bone area; 3=Severe osteolysis, defined as completely osteolytic bone. Histological Analysis: H&E and TRAP staining was performed on tissue to confirm the micro-CT findings and to quantify osteoclasts. Statistical Analysis: Inter-rater analysis was performed using Cohen9s kappa analysis. An inter-rater coefficient >0.65 was considered as high inter-rater agreement. Comparison between groups was made using one-way ANOVA with post hoc Bonferroni correction for multiple comparisons. Correlations are reported as Spearman9s rho. A p-value Results More than 83% of the VE-UHMWPE and more than 85% of the virgin UHMWPE particles measured less than 1 µm in mean particle size. The mean particle size for VE-UHMWPE was 1.12 µm (range 0.28 to 79.08 µm), while virgin UHMWPE particles measured 1.22 µm (range 0.28 to 82.04 µm). There was a statistically significant greater level of osteolysis visualized on the topographical grading scale in calvaria implanted with virgin UHMWPE wear particles. The micro-CT findings were confirmed histologically. A greater amount of inflammatory tissue overlaying the calvaria was observed in the virgin UHMWPE group when compared to both shams and VE-UHMWPE groups. Post hoc analysis revealed significant difference between VE-UHMWPE and virgin UHMWPE for the topographical osteolysis grading score (p = 0.002) but no difference in osteoclast count (p = 0.293). Discussion/Conclusion This is the first in vivo study reporting the effects of clinically-relevant UHMWPE particles generated from a VE-UHMWPE implant that is in current clinical use. These results suggest that VE-UHMWPE particles have reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model. Arthroplasty procedures using VE-UHMWPE might be less susceptible to peri-prosthetic loosening caused by wear Debris.

  • third body wear testing of a highly cross linked acetabular liner the effect of large femoral head size in the presence of Particulate poly methyl methacrylate Debris
    Journal of Arthroplasty, 2005
    Co-Authors: Charles R. Bragdon, Murali Jasty, Orhun K. Muratoglu, William H. Harris
    Abstract:

    Abstract The hip simulator wear performance of an electron beam cross-linked and subsequently melted ultrahigh molecular weight polyethylene against femoral heads of 28-, 38-, and 46-mm diameter in the presence of poly(methyl-methacrylate) Particulate Debris was contrasted with that of conventional polyethylene against a 46-mm diameter head. Over 5 million cycles of testing, the average wear rate of the conventional polyethylene liners was 29.3 ± 3.0 mg per million cycles. All highly cross-linked components exhibited marked reduction in wear, with the highest wear measuring 0.74 ± 0.85 mg per million cycles. This study, using a clinically relevant third-body material, showed the electron beam cross-linked material to be far more resistant to this third-body wear than conventional ultrahigh molecular weight polyethylene, even when very large diameter femoral heads were used.

  • third body wear of highly cross linked polyethylene in a hip simulator
    Journal of Arthroplasty, 2003
    Co-Authors: Charles R. Bragdon, Daniel O Oconnor, Murali Jasty, Orhun K. Muratoglu, William H. Harris
    Abstract:

    Abstract The wear performance of a radiation cross-linked melted ultrahigh-molecular-weight polyethylene (UHMWPE) articulating against 28-mm cobalt chrome femoral heads in the presence of third-body Particulate Debris was investigated in a hip simulator and compared with the wear of conventional UHMWPE. Particles of aluminum oxide or bone cement containing barium sulfate were added to the serum. In the presence of aluminum oxide particles, the incremental wear rates of conventional UHMWPE averaged as high as 149 ± 116 mg/million cycles compared with 37 ± 38 mg/million cycles for the highly cross-linked components. The difference in the average weight loss was statistically significant at P

Peter L. Faries - One of the best experts on this subject based on the ideXlab platform.

  • predicting embolic potential during carotid angioplasty and stenting analysis of captured Particulate Debris ultrasound characteristics and prior carotid endarterectomy
    Journal of Vascular Surgery, 2010
    Co-Authors: Rajesh Malik, Gregg S Landis, Scott Sundick, Neal S Cayne, Michael L Marin, Peter L. Faries
    Abstract:

    Introduction Extracranial carotid stenoses exhibit significant variance in embolic potential, with restenotic lesions having a particularly low propensity for embolization. This study sought to identify characteristics associated with increased generation of embolic Debris during carotid angioplasty and stenting (CAS). Methods Captured Particulate was available for analysis in 56 consecutive patients. Demographics were mean age, 74 years (range, 60-94 years); mean stenosis, 88% (range, 70%-99%); symptomatic, 27%; prior carotid endarterectomy (CEA), 27%; prior radiotherapy, 7%. Plaque echogenicity, heterogenicity, ulceration, and irregularity were assessed with B-mode duplex ultrasound analysis. Gray scale median (GSM) was calculated from normalized B-mode VHS video recordings. Calcification and degree of stenosis were determined angiographically. Captured Particulate Debris was evaluated for total number; number >200 μm, >500 μm, >1000 μm; mean and median size. Hematoxylin and eosin, trichrome, and von Kossa stains were used for histologic analysis of captured material. Results Restenotic carotid stenoses after prior CEA generated minimal embolic Debris compared with primary stenoses. Four of 15 patients (27%) with restenotic lesions demonstrated embolic particles; all Debris was 200 μm in 91%, >500 μm in 72%, and >1000 μm in 43%. In primary lesions, the number and size of captured Particulate correlated with GSM and with the combined ultrasound findings of echogenicity, heterogenicity, and luminal irregularity/ulceration ( P P = NS). Patients aged >70 years exhibited more total particles (8.1 vs 2.3, P = .008) and increased mean particle size (370 vs 157 μm, P = .02). No significant correlation was observed between the number and size of captured embolic Particulate and any other variable (stenosis percentage, prior radiotherapy, preprocedural symptoms, periprocedural symptoms, and calcification). Histologically, the embolic Debris consisted of extensive amorphous, acellular proteinaceous material. Calcium Debris in the embolic Particulate was associated with heavily and moderately calcified lesions. Conclusions Considerable variation exists in the number and size of embolic particles generated during CAS. Embolic potential is positively correlated with lesion GSM and the combination of lesion echogenicity, heterogenicity, and irregularity. Restenosis after prior CEA is associated with minimal embolic Particulate generation, suggesting that embolic protection may not be necessary for CAS of restenotic lesions.

  • Determining the quantity and character of carotid artery embolic Debris by electron microscopy and energy dispersive spectroscopy
    Journal of vascular surgery, 2007
    Co-Authors: Brian G. Derubertis, R E Gordon, Rabih A. Chaer, Heather M. Bell, Robert L. Hynecek, Fred M. Pieracci, John K. Karwowski, K. Craig Kent, Peter L. Faries
    Abstract:

    Objectives Carotid artery angioplasty and stenting (CAS) is now routinely performed with embolic protection devices, yet little is known about the compositional characteristics of the captured embolic Debris and whether the type or quantity of Debris correlates with patient, lesion, or operator characteristics. This study examined the embolic Debris generated during CAS using electron microscopy and energy dispersive spectroscopy (EDS) for symptomatic and asymptomatic patients. Methods Between 2003 and 2005, CAS for carotid stenosis was performed in 175 patients. Cerebral protection devices were used in all but three cases. Sixty-four consecutive unselected microporous filters from procedures performed by a single vascular surgeon were obtained for analysis. Captured Particulate Debris within the protection devices was quantified (number and mean size of particles) by light microscopy for all filters. Twenty protection devices (9 symptomatic, 11 asymptomatic patients) were processed for electron microscopy and EDS to assess morphology, cellular composition, and calcium content of Debris. Results Captured Particulate matter was present in 49 filters (77%) and included particles measuring 200 to 500 μm in 72%, 500 to 1000 μm in 53%, and >1000 μm in 33%. The mean number of captured particles was 6.9, and mean size was 248 ± 150 μm. Univariate analysis revealed that sequential patient cohort and filter type were correlated with the number (but not size) of captured particles. The number of particles significantly decreased after the first cohort of 20 patients (11.5 particles) compared with the second (5.0 particles, P = .023) and third (5.2 particles, P = .029) cohorts. The type of captured Debris ranged from sheets of damaged red blood cells without other components to clumps of recently activated platelets with early fibrin crosslinking to plaque Debris coated with well-organized coalescing areas of platelet thrombus. Platelet activation was more common in symptomatic patients (78%) than asymptomatic patients (27%; P Conclusions Particulate embolic Debris is released in most patients during CAS and can measure >1000 μm in one third of patients. The number of particles may decrease with increasing operator experience with CAS. Debris captured during CAS with embolic protection exhibits a range of cellular and acellular components on electron microscopy, with a higher prevalence of platelet activation evident in symptomatic patients.

Joshua J Jacobs - One of the best experts on this subject based on the ideXlab platform.

  • soluble ions more than Particulate cobalt alloy implant Debris induce monocyte costimulatory molecule expression and release of proinflammatory cytokines critical to metal induced lymphocyte reactivity
    Journal of Biomedical Materials Research Part A, 2009
    Co-Authors: Marco S Caicedo, Kyron Mcallister, Joshua J Jacobs, P H Pennekamp, Nadim J Hallab
    Abstract:

    Aseptic osteolysis has been associated with excessive immune reactivity to Particulate implant Debris; however, innate and adaptive immune mechanisms that underlie implant Debris reactivity remain incompletely understood. Although Particulate Debris has been implicated as the major type of implant Debris mediating macrophage-induced osteolysis, the degree to which metal ions affect a proinflammatory response (if at all) remains unknown. We hypothesized that both soluble and Particulate metal implant Debris will induce proinflammatory responses in human monocytes resulting in cytokine production and elevated expression of T cell costimulatory molecules, facilitating adaptive immune responses. We tested this hypothesis by characterizing the response of a human monocyte cell line (THP-1), isolated primary human monocytes and PBMCs challenged with Co-Cr-Mo alloy particles and soluble cobalt, chromium, molybdenum, and nickel ions. Our results indicate that soluble cobalt, nickel, and molybdenum can induce monocyte up-regulation of T cell costimulatory molecules (CD80, CD86, ICAM-1) in human monocytes/macrophages. Furthermore, cobalt, molybdenum ions, and Co-Cr-Mo alloy particles similarly induce elevated secretion of IL-1β, TNFα, and IL-6. Antibody blockade of CD80 and CD86, crucial secondary molecules for adaptive responses, abrogated lymphocyte reactivity to metal challenge in metal reactive subjects. Also the addition of IL-1 receptor antagonist (IL-1ra), (which indirectly blocks pro-IL-1β and thus IL-1β release), significantly reduced lymphocyte reactivity in metal-reactive subjects. Thus, both soluble and Particulate metal implant Debris induce monocyte/macrophage proinflammatory responses that are metal and individual specific. This suggests metal-induced up-regulation of costimulatory molecules and proinflammatory cytokine production is necessary to induce lymphocyte activation/proliferation to metal implant Debris. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010

  • biologic effects of implant Debris
    Bulletin of the NYU hospital for joint diseases, 2009
    Co-Authors: Nadim J Hallab, Joshua J Jacobs
    Abstract:

    Biologic response to orthopedic implants Debris is central to clinical performance. Eventual implant loosening due to aseptic osteolysis has been attributed to local inflammatory responses to wear and corrosion products that are produced by articulating implant interfaces. The response to implant Debris is dominated by local immune activation, e.g. macrophages. Immune reactivity has been shown to depend on the number of particles produced or the dose (i.e., the concentration of phagocytosable particles per tissue volume, which can be characterized by knowing the size distribution and amount of Debris). Elongated particles (fbers) are generally more pro-inflammatory than round particles, and there is a growing consensus that metals particles are more proinflammatory than polymers in vivo. Generally, to produce an in vitro inflammatory response, particles need to be less than 10 mum, i.e. phagocytosable. However, both soluble and Particulate Debris derived from Co-Cr-Mo alloy implants can induce monocyte/macrophage activation and secretion of pro-inflammatory cytokines such as IL-1beta, TNFalpha, IL-6 and IL-8 via up-regulation of transcription factor NFkappabeta, and activation of inflammasome danger signaling in human macrophages. Not only does activation of local (and systemic) inflammation result in decreased osteoblast function but osteoclast activity increases. Some people are more predisposed to implant Debris induced inflammation and metal "allergy" testing services are becoming available. New pathways of implant Debris-induced inflammatory reactions continue to be discovered, such as the "danger signaling" inflammasome pathway, which provides new targets for pharmaceutical intervention and improved implant performance.

  • modes of wear after semiconstrained total elbow arthroplasty
    Journal of Bone and Joint Surgery American Volume, 2008
    Co-Authors: Steven H Goldberg, Joshua J Jacobs, Robert M Urban, Shawn W Odriscoll, Graham J W King, Mark S Cohen
    Abstract:

    Background: Osteolysis and aseptic loosening are increasingly recognized complications of total elbow arthroplasty. However, unlike the literature on total hip and knee arthroplasty, studies describing the mechanisms of these processes after total elbow arthroplasty are sparse. Methods: Semiconstrained total elbow arthroplasty components were retrieved from sixteen elbows (fourteen patients) at either revision surgery (at a mean of five years after implantation) for mechanical failure (fifteen elbows) or postmortem examination (one elbow). In all cases, the retrieved implant was the primary implant. The patterns of damage on these components were investigated with stereomicroscopy in correlation with clinical findings, serial radiographs, and histopathological observations. Results: All of the retrieved devices exhibited multiple modes of wear. Damage to the humeral and ulnar polyethylene bushings was nearly universal; twenty-seven of twenty-eight humeral bushings demonstrated asymmetrical thinning, while fifteen of sixteen ulnar bushings demonstrated elliptical plastic deformation. In addition, unintended metal-on-metal wear between bearing and nonbearing surfaces or between two nonbearing surfaces was commonly observed, typically in association with wear and deformation of the polyethylene bushings. Wear between the stem and the cement mantle was observed in most of the ulnar components. The histopathology of the periprosthetic tissues was similar in character to that observed in association with osteolysis and loosening of total hip and knee replacements, while analysis of the Particulate Debris revealed a preponderance of titanium alloy and polyethylene Debris. Barium sulfate particles were also observed to a lesser extent. Conclusions: Multimodal wear in total elbow replacements can lead to osteolysis, aseptic loosening, and prosthetic and periprosthetic fracture necessitating revision surgery. Polyethylene wear and damage, as well as unintended metal-on-metal wear, contribute to the periprosthetic Particulate burden, which is likely pathogenic in these processes.

  • spinal implant Debris induced osteolysis
    Spine, 2003
    Co-Authors: Nadim J Hallab, Brian W Cunningham, Joshua J Jacobs
    Abstract:

    STUDY DESIGN: Generally, implant-induced osteolysis is a manifestation of an adverse cellular response to phagocytosable Particulate wear and corrosion Debris. Initially termed "cement disease," particle-induced loosening was recognized by Charnley in the early 1960s. Despite the plethora of information gained over the last 40 years on the basic science of periprosthetic bone loss, much remains unanswered. The effect of unintended Debris resulting from wear and corrosion (e.g., micromotion between the interconnection mechanisms in spinal implants) remains a clinical concern. The current study highlights what is known of particle-induced osteolysis and how the presence of spinal implant Particulate Debris deleteriously influences osseointegration of posterolateral bone graft or disrupts an established posterolateral fusion mass. Tissue explant, animal, and cell culture studies have revealed the complexity of cellular reactivity involved in aseptic particle-induced osteolysis. OBJECTIVES: The objectives of this study are twofold: 1) to highlight the dominant cellular participants in total joint arthroplasty particle induced osteolysis, which are purportedly the macrophage, osteoblast, fibroblast, and osteoclast and several of the dominant chemical mediators have been identified as well, which include prostaglandin E2, tumor necrosis factor-alpha, interleukin-1, and interleukin-6; and 2) to demonstrate the potential deleterious effects of spinal implant Debris using animal models and analysis of soft tissue surrounding spinal implants in symptomatic patients. METHODS: There are a growing number of proinflammatory and anti-inflammatory cytokines, prostenoids, and enzymes that have been shown to play important roles in the pathology of particle-induced osteolysis. Reports that aseptic granulomatous inflammation typical of that associated with corrosion Debris appear to correlate with the complexity of the implant. Titanium Particulate material was used to induce effects in 34 New Zealand White rabbits where analysis included serological quantification of systemic cytokines. Postmortem microradiographic, immunocytochemical, and histopathologic assessment of the intertransverse fusion mass quantified the extent of osteolysis, local proinflammatory cytokines, osteoclasts and inflammatory infiltrates. Clinical analysis of 12 patients more than 0.4 years after spinal implants (mean 4.03, range 0.4 to 11 years) presented with late operative site pain. RESULTS: Currently the etiology of this inflammation around spinal implants resembles particle-induced osteolysis around joint arthroplasties where there typically is a self-perpetuating fibroinflammatory zone adjacent to the implant, where macrophage exhaustion, reactive oxygen intermediates, and pro-inflammatory cytokines affect a host of local cell types and induce a widening zone of soft tissue damage and inflammation. Animal model analysis indicated increased levels of local inflammatory cytokines typically associated with osteolysis-tumor necrosis factor-alpha. Osteoclast cell counts and regions of osteolytic resorption lacunas were higher in the titanium-treated versus autograft-alone groups (P < 0.05), and the extent of cellular apoptosis was markedly higher in the titanium-treated sites at both time intervals. Electron microscopy indicated definitive evidence of phagocytized titanium particles and foci of local, chronic inflammatory changes in the titanium-treated sites. CLINICAL CASES: 11 of 12 clinical cases demonstrated elevated tumor necrosis factor-alpha levels and an increased osteoclastic response in the vicinity of wear Debris caused by dry frictional wear particles of titanium or stainless steel. Resection of the wear Debris and surrounding fibroinflammatory zone resolved clinical symptoms in all 12 cases. CONCLUSIONS: More basic science and clinical research is needed to develop novel strategies for gaining knowledge, and developing effective evaluation and treatment of patients with implant Debris related osteolysis. Titanium Debris simulating that produced by spinal implants introduced at the level of a spinal arthrodesis elicits an inflammatory cytokine mediated Particulate-induced response through increased expression of intracellular TNF-alpha, increased osteoclastic activity and cellular apoptosis. This study highlighted the association between spinal implants Particulate wear Debris and increased potential for osteolysis. Aseptic osteolysis is among the primary reasons for failure of orthopedic implants. Increased awareness of this destructive process is becoming more important with the growing popularity of total disc arthroplasty and highly modular spinal implants.

  • concentration and composition dependent effects of metal ions on human mg 63 osteoblasts
    Journal of Biomedical Materials Research, 2002
    Co-Authors: Nadim J Hallab, Tibor T Glant, Kenneth A Roebuck, Csaba Vermes, Carlo Messina, Joshua J Jacobs
    Abstract:

    Metal Debris from implants has been shown to alter the function of osteoblasts in cell cultures. Its remains unclear, however, if specific forms of released ionic metals are involved in the pathogenesis of periprosthetic osteolysis. We evaluated the relative effects of ionic forms of implant metals by treating human osteoblast-like MG-63 osteosarcoma cells with eight concentrations (0.001-10.0 mM) of Cr(+3), Mo(+5), Al(+3), Ta(+5), Co(+2), Ni(+2), Fe(+3), Cu(+2), Mn(+2), Mg(+2), Na(+2), and V(+3) chloride solutions. The results demonstrated that the metal ions differentially affected osteoblast proliferation, viability, type-I collagen gene expression, and cytokine release. The metal ions were ranked in order from least to most toxic (based on a 50% reduction in viability) as follows: Na < Cr < Mg < Mo < Al < Ta < Co < Ni < Fe < Cu < Mn < V. Metal-induced decreases in osteoblast proliferation were similar in ranking. Nontoxic concentrations of metals had no effect on procollagen alpha1[I] gene expression; only at toxic concentrations did metals produce a decrease in gene expression. The most toxic metals (V, Mn, Fe, and Ni) were also the only metals found to induce IL-6 secretion on a per cell basis (of the cytokines tested, interleukin 6 (IL-6), interleukin beta 1 (IL-1beta), transforming growth factor beta 1 (TGF-beta1), and tumor necrosis factor alpha (TNF-alpha), only IL-6 was detectable in the culture medium after 48 h for any metal at any concentration). Less toxic metals (e.g., Co and Cr) had little effect on IL-6 release, even at high concentrations. In general, metal ions reduced osteoblast function (i.e., proliferation and collagen gene expression) in proportion to the degree of toxicity. These results support the hypothesis that adverse local cellular responses (particularly necrotic responses) associated with metal Debris from implanted metallic devices may be due in part to metal ions released from implants or from Particulate Debris.

William H. Harris - One of the best experts on this subject based on the ideXlab platform.

  • third body wear testing of a highly cross linked acetabular liner the effect of large femoral head size in the presence of Particulate poly methyl methacrylate Debris
    Journal of Arthroplasty, 2005
    Co-Authors: Charles R. Bragdon, Murali Jasty, Orhun K. Muratoglu, William H. Harris
    Abstract:

    Abstract The hip simulator wear performance of an electron beam cross-linked and subsequently melted ultrahigh molecular weight polyethylene against femoral heads of 28-, 38-, and 46-mm diameter in the presence of poly(methyl-methacrylate) Particulate Debris was contrasted with that of conventional polyethylene against a 46-mm diameter head. Over 5 million cycles of testing, the average wear rate of the conventional polyethylene liners was 29.3 ± 3.0 mg per million cycles. All highly cross-linked components exhibited marked reduction in wear, with the highest wear measuring 0.74 ± 0.85 mg per million cycles. This study, using a clinically relevant third-body material, showed the electron beam cross-linked material to be far more resistant to this third-body wear than conventional ultrahigh molecular weight polyethylene, even when very large diameter femoral heads were used.

  • third body wear of highly cross linked polyethylene in a hip simulator
    Journal of Arthroplasty, 2003
    Co-Authors: Charles R. Bragdon, Daniel O Oconnor, Murali Jasty, Orhun K. Muratoglu, William H. Harris
    Abstract:

    Abstract The wear performance of a radiation cross-linked melted ultrahigh-molecular-weight polyethylene (UHMWPE) articulating against 28-mm cobalt chrome femoral heads in the presence of third-body Particulate Debris was investigated in a hip simulator and compared with the wear of conventional UHMWPE. Particles of aluminum oxide or bone cement containing barium sulfate were added to the serum. In the presence of aluminum oxide particles, the incremental wear rates of conventional UHMWPE averaged as high as 149 ± 116 mg/million cycles compared with 37 ± 38 mg/million cycles for the highly cross-linked components. The difference in the average weight loss was statistically significant at P

  • the problem is osteolysis
    Clinical Orthopaedics and Related Research, 1995
    Co-Authors: William H. Harris
    Abstract:

    Recent studies have generated considerable information that reveals substantial support for major change in the understanding of total hip arthroplasty and its current state. Although some of these observations appear unrelated at first glance, they can be drawn together to support the thesis that osteolysis is the dominant problem in total hip arthroplasty. These observations are as follows: (1) Five-year followup data are required for a minimum assessment of a new concept in total hip design and material because osteolysis is uncommon before that time. (2) Excellent fixation can be achieved on the femoral side with good cementing and good cementless techniques. Thus, femoral component loosening is less of an issue currently. (3) Many acetabular components become loose because of the ingress of Particulate Debris that leads to linear bone loss at the interface with the pelvis, a process that is biologically akin to the more florid forms of osteolysis. Thus, much acetabular component loosening represents a form of osteolysis. (4) Many cementless femoral reconstructions have developed a high incidence of femoral osteolysis. (5) Many cementless sockets have developed a high incidence of pelvic osteolysis. Taken in conjunction, these observations suggest that periprosthetic osteolysis is the leading problem in contemporary total hip replacement.

  • periprosthetic bone loss in total hip arthroplasty polyethylene wear Debris and the concept of the effective joint space
    Journal of Bone and Joint Surgery American Volume, 1992
    Co-Authors: Thomas P Schmalzried, Murali Jasty, William H. Harris
    Abstract:

    Thirty-four hips in which there had been prosthetic replacement were selected for study because of the presence of linear (diffuse) or lytic (localized) areas of periprosthetic bone loss. In all hips, there was careful documentation of the anatomical location of the material that had been obtained for histological analysis, and the specific purpose of the removal of the tissue was for examination to determine the cause of the resorption of bone. Specimens from twenty-three hips were retrieved during an operation and from eleven hips, at autopsy. The area of bone loss was linear only in sixteen hips, lytic only in thirteen, and both linear and lytic in five. In all thirty-four hips, intracellular Particulate Debris was found in the macrophages that were present in the area of bone resorption. All thirty-four had intracellular particles of polyethylene, many of which were less than one micrometer in size. Thirty-one hips had extracellular particles of polyethylene as well. Twenty-two of the thirty-four hips had intracellular metallic Debris; in ten, metallic Debris was found extracellularly as well. Ten of the sixteen cemented specimens had intracellular and extracellular polymethylmethacrylate Debris. In the mechanically stable prostheses--cemented and uncemented--polyethylene wear Debris was identified in areas of bone resorption far from the articular surfaces. The number of macrophages in a microscopic field was directly related to the amount of Particulate polyethylene Debris that was visible by light microscopy. Although the gross radiographic appearances of linear bone loss and lytic bone loss were different, the histological appearance of the regions in which there was active bone resorption was similar. Regardless of the radiographic appearance and anatomical origin of the specimen, bone resorption was found to occur in association with macrophages that were laden with polyethylene Debris. In general, the number of macrophages present had a direct relationship to the degree of bone resorption that was seen. We believe that these findings indicate that joint fluid penetrates far more extensively than previously thought, even in a well fixed component, along the interface between the prosthesis and bone and in the periprosthetic tissues; it is often more extensive than is shown by arthrography. We therefore suggest the concept of the effective joint space to include all periprosthetic regions that are accessible to joint fluid and thus accessible to Particulate Debris.(ABSTRACT TRUNCATED AT 400 WORDS)

Nadim J Hallab - One of the best experts on this subject based on the ideXlab platform.

  • the inflammatory effects of breast implant Particulate shedding comparison with orthopedic implants
    Aesthetic Surgery Journal, 2019
    Co-Authors: Nadim J Hallab, Lauryn Samelko, Dennis C Hammond
    Abstract:

    : Currently, there is a dearth of information regarding the degree of particle shedding from breast implants (BIs) and what are the general biological consequences of BI Debris. Thus, it is unclear to what degree BI Debris compromises the long-term biological performance of BIs. For orthopedic implants, it is well established that the severity of biological reactivity to implant Debris governs long-term clinical performance. Orthopedic implant Particulate Debris is generally in the range of 0.01 to 100 μm in diameter. Implant Debris-induced bioreactivity/inflammation is mostly a peri-implant phenomenon caused by local innate immune cells (eg, macrophages) that produce proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-6, and prostaglandin 2 (PGE2). In orthopedics, there have been few systemic concerns associated with polymeric implant Debris (like silicone) other than documented dissemination to remote organs (eg, liver, spleen, etc.) with no known associated pathogenicity. This is not true of metal implant Debris where normal (well-functioning) implants can induce systemic reactions such as delayed type hypersensitivity. Diagnostic analysis of orthopedic tissues has focused on innate (macrophage mediated) and adaptive (lymphocyte-mediated hypersensitivity) immune responses. Orthopedic implant Debris-associated lymphocyte cancers have not been reported in over 40 years of orthopedic literature. Adaptive immune responses such as hypersensitivity reactions to orthopedic implant Debris have been dominated by certain implant types that produce specific kinds of Debris (eg, metal-on-metal total joint prostheses). Orthopedic hypersensitivity responses and atypical BI bioreactivity such as BI-associated anaplastic large cell lymphoma share crossover markers for diagnosis. Differentiating normal innate immune reactivity to particles from anaplastic large cell lymphoma reactions from delayed type hypersensitivity reactions to BI-associated implant Debris remains unclear but vital to patients and surgeons.

  • epidural application of spinal instrumentation Particulate wear Debris a comprehensive evaluation of neurotoxicity using an in vivo animal model
    Journal of Neurosurgery, 2013
    Co-Authors: Bryan W Cunningham, Nadim J Hallab, Paul C Mcafee
    Abstract:

    Object The introduction and utilization of motion-preserving implant systems for spinal reconstruction served as the impetus for this basic scientific investigation. The effect of unintended wear Particulate Debris resulting from micromotion at spinal implant interconnections and bearing surfaces remains a clinical concern. Using an in vivo rabbit model, the current study quantified the neural and systemic histopathological responses following epidural application of 11 different types of medical-grade Particulate wear Debris produced from spinal instrumentation. Methods A total of 120 New Zealand White rabbits were equally randomized into 12 groups based on implant treatment: 1) sham (control), 2) stainless steel, 3) titanium alloy, 4) cobalt chromium alloy, 5) ultra–high molecular weight polyethylene (UHMWPe), 6) ceramic, 7) polytetrafluoroethylene, 8) polycarbonate urethane, 9) silicone, 10) polyethylene terephthalate, 11) polyester, and 12) polyetheretherketone. The surgical procedure consisted of a m...

  • soluble ions more than Particulate cobalt alloy implant Debris induce monocyte costimulatory molecule expression and release of proinflammatory cytokines critical to metal induced lymphocyte reactivity
    Journal of Biomedical Materials Research Part A, 2009
    Co-Authors: Marco S Caicedo, Kyron Mcallister, Joshua J Jacobs, P H Pennekamp, Nadim J Hallab
    Abstract:

    Aseptic osteolysis has been associated with excessive immune reactivity to Particulate implant Debris; however, innate and adaptive immune mechanisms that underlie implant Debris reactivity remain incompletely understood. Although Particulate Debris has been implicated as the major type of implant Debris mediating macrophage-induced osteolysis, the degree to which metal ions affect a proinflammatory response (if at all) remains unknown. We hypothesized that both soluble and Particulate metal implant Debris will induce proinflammatory responses in human monocytes resulting in cytokine production and elevated expression of T cell costimulatory molecules, facilitating adaptive immune responses. We tested this hypothesis by characterizing the response of a human monocyte cell line (THP-1), isolated primary human monocytes and PBMCs challenged with Co-Cr-Mo alloy particles and soluble cobalt, chromium, molybdenum, and nickel ions. Our results indicate that soluble cobalt, nickel, and molybdenum can induce monocyte up-regulation of T cell costimulatory molecules (CD80, CD86, ICAM-1) in human monocytes/macrophages. Furthermore, cobalt, molybdenum ions, and Co-Cr-Mo alloy particles similarly induce elevated secretion of IL-1β, TNFα, and IL-6. Antibody blockade of CD80 and CD86, crucial secondary molecules for adaptive responses, abrogated lymphocyte reactivity to metal challenge in metal reactive subjects. Also the addition of IL-1 receptor antagonist (IL-1ra), (which indirectly blocks pro-IL-1β and thus IL-1β release), significantly reduced lymphocyte reactivity in metal-reactive subjects. Thus, both soluble and Particulate metal implant Debris induce monocyte/macrophage proinflammatory responses that are metal and individual specific. This suggests metal-induced up-regulation of costimulatory molecules and proinflammatory cytokine production is necessary to induce lymphocyte activation/proliferation to metal implant Debris. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010

  • biologic effects of implant Debris
    Bulletin of the NYU hospital for joint diseases, 2009
    Co-Authors: Nadim J Hallab, Joshua J Jacobs
    Abstract:

    Biologic response to orthopedic implants Debris is central to clinical performance. Eventual implant loosening due to aseptic osteolysis has been attributed to local inflammatory responses to wear and corrosion products that are produced by articulating implant interfaces. The response to implant Debris is dominated by local immune activation, e.g. macrophages. Immune reactivity has been shown to depend on the number of particles produced or the dose (i.e., the concentration of phagocytosable particles per tissue volume, which can be characterized by knowing the size distribution and amount of Debris). Elongated particles (fbers) are generally more pro-inflammatory than round particles, and there is a growing consensus that metals particles are more proinflammatory than polymers in vivo. Generally, to produce an in vitro inflammatory response, particles need to be less than 10 mum, i.e. phagocytosable. However, both soluble and Particulate Debris derived from Co-Cr-Mo alloy implants can induce monocyte/macrophage activation and secretion of pro-inflammatory cytokines such as IL-1beta, TNFalpha, IL-6 and IL-8 via up-regulation of transcription factor NFkappabeta, and activation of inflammasome danger signaling in human macrophages. Not only does activation of local (and systemic) inflammation result in decreased osteoblast function but osteoclast activity increases. Some people are more predisposed to implant Debris induced inflammation and metal "allergy" testing services are becoming available. New pathways of implant Debris-induced inflammatory reactions continue to be discovered, such as the "danger signaling" inflammasome pathway, which provides new targets for pharmaceutical intervention and improved implant performance.

  • spinal implant Debris induced osteolysis
    Spine, 2003
    Co-Authors: Nadim J Hallab, Brian W Cunningham, Joshua J Jacobs
    Abstract:

    STUDY DESIGN: Generally, implant-induced osteolysis is a manifestation of an adverse cellular response to phagocytosable Particulate wear and corrosion Debris. Initially termed "cement disease," particle-induced loosening was recognized by Charnley in the early 1960s. Despite the plethora of information gained over the last 40 years on the basic science of periprosthetic bone loss, much remains unanswered. The effect of unintended Debris resulting from wear and corrosion (e.g., micromotion between the interconnection mechanisms in spinal implants) remains a clinical concern. The current study highlights what is known of particle-induced osteolysis and how the presence of spinal implant Particulate Debris deleteriously influences osseointegration of posterolateral bone graft or disrupts an established posterolateral fusion mass. Tissue explant, animal, and cell culture studies have revealed the complexity of cellular reactivity involved in aseptic particle-induced osteolysis. OBJECTIVES: The objectives of this study are twofold: 1) to highlight the dominant cellular participants in total joint arthroplasty particle induced osteolysis, which are purportedly the macrophage, osteoblast, fibroblast, and osteoclast and several of the dominant chemical mediators have been identified as well, which include prostaglandin E2, tumor necrosis factor-alpha, interleukin-1, and interleukin-6; and 2) to demonstrate the potential deleterious effects of spinal implant Debris using animal models and analysis of soft tissue surrounding spinal implants in symptomatic patients. METHODS: There are a growing number of proinflammatory and anti-inflammatory cytokines, prostenoids, and enzymes that have been shown to play important roles in the pathology of particle-induced osteolysis. Reports that aseptic granulomatous inflammation typical of that associated with corrosion Debris appear to correlate with the complexity of the implant. Titanium Particulate material was used to induce effects in 34 New Zealand White rabbits where analysis included serological quantification of systemic cytokines. Postmortem microradiographic, immunocytochemical, and histopathologic assessment of the intertransverse fusion mass quantified the extent of osteolysis, local proinflammatory cytokines, osteoclasts and inflammatory infiltrates. Clinical analysis of 12 patients more than 0.4 years after spinal implants (mean 4.03, range 0.4 to 11 years) presented with late operative site pain. RESULTS: Currently the etiology of this inflammation around spinal implants resembles particle-induced osteolysis around joint arthroplasties where there typically is a self-perpetuating fibroinflammatory zone adjacent to the implant, where macrophage exhaustion, reactive oxygen intermediates, and pro-inflammatory cytokines affect a host of local cell types and induce a widening zone of soft tissue damage and inflammation. Animal model analysis indicated increased levels of local inflammatory cytokines typically associated with osteolysis-tumor necrosis factor-alpha. Osteoclast cell counts and regions of osteolytic resorption lacunas were higher in the titanium-treated versus autograft-alone groups (P < 0.05), and the extent of cellular apoptosis was markedly higher in the titanium-treated sites at both time intervals. Electron microscopy indicated definitive evidence of phagocytized titanium particles and foci of local, chronic inflammatory changes in the titanium-treated sites. CLINICAL CASES: 11 of 12 clinical cases demonstrated elevated tumor necrosis factor-alpha levels and an increased osteoclastic response in the vicinity of wear Debris caused by dry frictional wear particles of titanium or stainless steel. Resection of the wear Debris and surrounding fibroinflammatory zone resolved clinical symptoms in all 12 cases. CONCLUSIONS: More basic science and clinical research is needed to develop novel strategies for gaining knowledge, and developing effective evaluation and treatment of patients with implant Debris related osteolysis. Titanium Debris simulating that produced by spinal implants introduced at the level of a spinal arthrodesis elicits an inflammatory cytokine mediated Particulate-induced response through increased expression of intracellular TNF-alpha, increased osteoclastic activity and cellular apoptosis. This study highlighted the association between spinal implants Particulate wear Debris and increased potential for osteolysis. Aseptic osteolysis is among the primary reasons for failure of orthopedic implants. Increased awareness of this destructive process is becoming more important with the growing popularity of total disc arthroplasty and highly modular spinal implants.