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      Simvastatin-hydroxyapatite coatings prevent biofilm formation and improve bone formation in implant-associated infections

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          Abstract

          Implant-associated infections (IAIs) caused by biofilm formation are the most devastating complications of orthopedic surgery. Statins have been commonly and safely used drugs for hypercholesterolemia for many years. Here, we report that simvastatin-hydroxyapatite-coated titanium alloy prevents biofilm-associated infections. The antibacterial properties of simvastatin against Staphylococcus aureus and Staphylococcus epidermidis biofilms in vitro was confirmed by crystal violet staining and live-dead bacterial staining. We developed a simvastatin-and hydroxyapatite (Sim-HA)-coated titanium alloy via electrochemical deposition. Sim-HA coatings inhibited Staphylococcus aureus biofilm formation and improved the biocompatibility of the titanium alloy. Sim-HA coatings effectively prevented Staphylococcus aureus IAI in rat femurs, as confirmed by radiological assessment and histological examination. The antibacterial effects of the Sim-HA coatings were attributed to their inhibitory effects on biofilm formation, as verified by scanning electron microscopic observations and bacterial spread plate analysis. In addition, the Sim-HA coatings enhanced osteogenesis and osteointegration, as verified by micro-CT, histological evaluation, and biomechanical pull-out tests. In summary, Sim-HA coatings are promising implant materials for protection against biofilm-associated infections.

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          Highlights

          • Simvastatin-hydroxyapatite coatings were prepared on Ti6Al4V by electrochemical deposition process.

          • The Simvastatin-hydroxyapatite coatings inhibited S. aureus biofilm formation and improved biocompatibility in vitro.

          • The coatings exhibited antibacterial effects and improved bone formation in a rat femur IAI model.

          • Simvastatin coatings are promising for application in orthopedic implants.

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          Most cited references67

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          Bacterial biofilms: from the natural environment to infectious diseases.

          Biofilms--matrix-enclosed microbial accretions that adhere to biological or non-biological surfaces--represent a significant and incompletely understood mode of growth for bacteria. Biofilm formation appears early in the fossil record (approximately 3.25 billion years ago) and is common throughout a diverse range of organisms in both the Archaea and Bacteria lineages, including the 'living fossils' in the most deeply dividing branches of the phylogenetic tree. It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments. Recent advances show that biofilms are structurally complex, dynamic systems with attributes of both primordial multicellular organisms and multifaceted ecosystems. Biofilm formation represents a protected mode of growth that allows cells to survive in hostile environments and also disperse to colonize new niches. The implications of these survival and propagative mechanisms in the context of both the natural environment and infectious diseases are discussed in this review.
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            Periprosthetic joint infection.

            Periprosthetic joint infections are a devastating complication after arthroplasty and are associated with substantial patient morbidity. More than 25% of revisions are attributed to these infections, which are expected to increase. The increased prevalence of obesity, diabetes, and other comorbidities are some of the reasons for this increase. Recognition of the challenge of surgical site infections in general, and periprosthetic joint infections particularly, has prompted implementation of enhanced prevention measures preoperatively (glycaemic control, skin decontamination, decolonisation, etc), intraoperatively (ultraclean operative environment, blood conservation, etc), and postoperatively (refined anticoagulation, improved wound dressings, etc). Additionally, indications for surgical management have been refined. In this Review, we assess risk factors, preventive measures, diagnoses, clinical features, and treatment options for prosthetic joint infection. An international consensus meeting about such infections identified the best practices and further research needs. Orthopaedics could benefit from enhanced preventive, diagnostic, and treatment methods.
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              Biomaterial-centered infection: microbial adhesion versus tissue integration.

              A Gristina (1987)
              Biomaterials are being used with increasing frequency for tissue substitution. Complex devices such as total joint replacements and the total artificial heart represent combinations of polymers and metal alloys for system and organ replacement. The major barriers to the extended use of these devices are the possibility of bacterial adhesion to biomaterials, which causes biomaterial-centered infection, and the lack of successful tissue integration or compatibility with biomaterial surfaces. Interactions of biomaterials with bacteria and tissue cells are directed not only by specific receptors and outer membrane molecules on the cell surface, but also by the atomic geometry and electronic state of the biomaterial surface. An understanding of these mechanisms is important to all fields of medicine and is derived from and relevant to studies in microbiology, biochemistry, and physics. Modifications to biomaterial surfaces at an atomic level will allow the programming of cell-to-substratum events, thereby diminishing infection by enhancing tissue compatibility or integration, or by directly inhibiting bacterial adhesion.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                13 August 2022
                March 2023
                13 August 2022
                : 21
                : 44-56
                Affiliations
                [a ]Department of Orthopedics, Peking University Third Hospital, Beijing, China
                [b ]Beijing Key Laboratory of Spinal Diseases, Beijing, China
                [c ]Engineering Research Center of Bone and Joint Precision Medicine, Ministry of Education, Beijing, China
                [d ]Institute of Medical Sciences, The Second Hospital of Shandong University, Jinan, China
                Author notes
                []Corresponding author. Peking University Third Hospital, Beijing, 100191, China. schl@ 123456bjmu.edu.cn
                Article
                S2452-199X(22)00330-9
                10.1016/j.bioactmat.2022.07.028
                9395756
                36017072
                5528f416-3479-4ce4-b482-51eb7a868451
                © 2022 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 26 February 2022
                : 18 July 2022
                : 29 July 2022
                Categories
                Article

                implant-associated infections,simvastatin,antibacterial,biofilm,osteogenesis

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