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      Therapeutics and Clinical Risk Management (submit here)

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      Is Open Access

      Bacterial Biofilm Components Induce an Enhanced Inflammatory Response Against Metal Wear Particles


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          Aseptic implant loosening is still a feared complication in the field of orthopaedics. Presumably, a chronic inflammatory response is induced by wear particles, which leads to osteoclast generation, bone degradation and hence loosening of the implant. Since it has been demonstrated in the literature that most implants are in fact colonized by bacteria, the question arises whether aseptic implant loosening is truly aseptic. The aim of this study was to investigate a possibly enhanced inflammatory response to metal wear particles in the context of subclinical infection.

          Patients and Methods

          Tissue samples were collected intra-operatively from patients undergoing implant-exchange surgery due to aseptic loosening. Histopathological analysis was performed, as well as gene expression analysis for the pro-inflammatory cytokine Interleukin-8. By a series of in vitro experiments, the effect of metal wear particles on human monocytes, polymorphonuclear neutrophiles and osteoblasts was investigated. Additionally, minor amounts of lipoteichoic acid (LTA) and the bacterial heat shock protein GroEL were added.


          Histopathology of tissue samples revealed an accumulation of metal wear particles, as well as a cellular infiltrate consisting predominately of mononuclear cells. Furthermore, high expression of IL-8 could be detected in tissue surrounding the implant. Monocytes and osteoblasts in particular showed an increased release of IL-8 after stimulation with metal wear particles and in particular after stimulation with bacterial components and wear particles together.


          We were able to show that minor amounts of bacterial components and metal wear particles together induce an enhanced inflammatory response in human monocytes and osteoblasts. This effect could significantly contribute to the generation of bone-resorbing osteoclasts and hence implant-loosening.

          Most cited references44

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          Antibiotic resistance of bacterial biofilms.

          A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and disinfectant chemicals as well as resisting phagocytosis and other components of the body's defence system. The persistence of, for example, staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is caused by biofilm-growing mucoid strains. Characteristically, gradients of nutrients and oxygen exist from the top to the bottom of biofilms and these gradients are associated with decreased bacterial metabolic activity and increased doubling times of the bacterial cells; it is these more or less dormant cells that are responsible for some of the tolerance to antibiotics. Biofilm growth is associated with an increased level of mutations as well as with quorum-sensing-regulated mechanisms. Conventional resistance mechanisms such as chromosomal beta-lactamase, upregulated efflux pumps and mutations in antibiotic target molecules in bacteria also contribute to the survival of biofilms. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy and they can be treated by chronic suppressive therapy. A promising strategy may be the use of enzymes that can dissolve the biofilm matrix (e.g. DNase and alginate lyase) as well as quorum-sensing inhibitors that increase biofilm susceptibility to antibiotics. (c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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            The operation of the century: total hip replacement.

            In the 1960s, total hip replacement revolutionised management of elderly patients crippled with arthritis, with very good long-term results. Today, young patients present for hip-replacement surgery hoping to restore their quality of life, which typically includes physically demanding activities. Advances in bioengineering technology have driven development of hip prostheses. Both cemented and uncemented hips can provide durable fixation. Better materials and design have allowed use of large-bore bearings, which provide an increased range of motion with enhanced stability and very low wear. Minimally invasive surgery limits soft-tissue damage and facilitates accelerated discharge and rehabilitation. Short-term objectives must not compromise long-term performance. Computer-assisted surgery will contribute to reproducible and accurate placement of implants. Universal economic constraints in healthcare services dictate that further developments in total hip replacement will be governed by their cost-effectiveness.
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              Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms


                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                08 December 2020
                : 16
                : 1203-1212
                [1 ]Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital , Heidelberg 69118, Germany
                [2 ]Department of Anesthesiology, Heidelberg University Hospital , Heidelberg 69120, Germany
                [3 ]Laboratory of Biomechanics and Implant Research, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital , Heidelberg 69118, Germany
                [4 ]Institute for Immunology, Heidelberg University , Heidelberg 69120, Germany
                Author notes
                Correspondence: Ulrike Dapunt Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital , Schlierbacher Landstrasse 200a, Heidelberg69118, GermanyTel + ±49-6221-56-25000 Email Ulrike.Dapunt@med.uni-heidelberg.de
                Author information
                © 2020 Dapunt et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                : 10 September 2020
                : 18 November 2020
                Page count
                Figures: 7, References: 44, Pages: 10
                Funded by: Heidelberg University Hospital;
                This study was funded by Heidelberg University Hospital.
                Original Research

                aseptic loosening,metal wear particles,biofilm,implant-associated infection,interleukin-8
                aseptic loosening, metal wear particles, biofilm, implant-associated infection, interleukin-8


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