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  • Lennerås, Maria, 1980, et al. (author)
  • The clinical, radiological, microbiological and molecular profile of the skin-penetration site of transfemoral amputees treated with bone-anchored prostheses.
  • 2017
  • In: Journal of Biomedical Materials Research. - : Wiley. - 0021-9304 .- 1097-4636 .- 1549-3296. ; 105:2, s. 578-589
  • Journal article (peer-reviewed)abstract
    • The breach of the skin barrier is a critical issue associated with the treatment of individuals with transfemoral amputation (TFA) using osseointegrated, percutaneous titanium implants. Thirty TFA patients scheduled for abutment exchange or removal were consecutively enrolled. The aims were to determine the macroscopic skin signs, the presence of bacteria and the gene expression in abutment-adherent cells and to conduct correlative and comparative analyses between the different parameters. Redness and a granulation ring were present in 47% of the patients. Bacteria were detected in 27/30 patients, commonly in the bone canal. Staphylococcus aureus, coagulase-negative staphylococci, streptococci, and Enterococcus faecalis were the most common. A positive correlation was found between TNF-α expression and the detection of S. aureus. Staphylococcus aureus together with other bacterial species revealed a positive relationship with MMP-8 expression. A negative correlation was demonstrated between the length of the residual femur bone and the detection of a granulation ring and E. faecalis. A positive correlation was revealed between fixture loosening and pain and the radiological detection of endosteal bone resorption. Fixture loosening was also correlated with the reduced expression of interleukin-10 and osteocalcin. It is concluded that several relationships exist between clinical, radiological, microbiological, and molecular assessments of the percutaneous area of TFAs. Further long term studies on larger patient cohorts are required to determine the precise cause-effect relationships and unravel the role of host-bacteria interactions in the skin, bone canal and on the abutment for the longevity of percutaneous implants as treatment of TFA. © 2016 Wiley Periodicals, Inc. J
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  • Akman, Adnan, et al. (author)
  • Effect of minor gallium addition on corrosion, passivity, and antibacterial behaviour of novel β-type Ti–Nb alloys
  • 2023
  • In: Journal of Materials Research and Technology. - 2238-7854. ; 25, s. 4110-4124
  • Journal article (peer-reviewed)abstract
    • Metastable Ti–Nb alloys are promising bone-implant materials due to improved mechanical biofunctionality and biocompatibility. To overcome increasing bacterial infection risk, alloying with antibacterial elements is a promising strategy. This study investigates the effect of minor gallium (Ga) additions (4, 8 wt% Ga) to as-cast and solution-treated β-type Ti–45Nb-based alloy (96(Ti–45Nb)-4Ga, 92(Ti–45Nb)-8Ga (wt.%)) on corrosion and passive film properties, as well as cytocompatibility and antibacterial activity. The electrochemical properties were evaluated by potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and Mott-Schottky analyses in phosphate-buffered saline (PBS). X-ray photoelectron spectroscopy (XPS) was performed to analyze the chemical composition of passive films. Early adhesion and viability of macrophages and Staphylococcus aureus were assessed by nucleocounting and colony-forming unit counting, respectively. The results showed that high corrosion resistance and passive film properties of Ti–45Nb are retained and even slightly improved with Ga. EIS results revealed that Ga addition improves the passive film resistance. XPS measurements of 92(Ti–45Nb)-8Ga show that the passive film contains Ti-, Nb- and Ga-based oxides, implying the formation of mixed (Ti–Nb-Ga) oxides. In addition, marginal Ga ion release rate was detected under free corrosion conditions. Therefore, it can be assumed that Ga species may contribute to passive film formation on Ga-containing alloys. The 92(Ti–45Nb)-8Ga elicited an antibacterial effect against S. aureus compared to cp-Ti at 4 h. Moreover, Ga-containing alloys showed good cytocompatibility with THP-1 macrophages at 24 h. In conclusion, it was demonstrated that Ga additions to Ti–45Nb are beneficial to corrosion resistance and showed promising initial host and bacterial interactions.
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  • Atefyekta, Saba, 1987, et al. (author)
  • Antimicrobial Peptide-Functionalized Mesoporous Hydrogels
  • 2021
  • In: ACS Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 7:4, s. 1693-1702
  • Journal article (peer-reviewed)abstract
    • Antimicrobial peptides (AMPs) are seen as a promising replacement to conventional antibiotics for the prevention of skin wound infections. However, due to the short half-life of AMPs in biological environments, such as blood, their use in clinical applications has been limited. The covalent immobilization of AMPs onto suitable substrates is an effective solution to create contact-killing surfaces with increased long-term stability. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was covalently attached to amphiphilic and ordered mesoporous Pluronic F127 hydrogels made of cross-linked lyotropic liquid crystals through 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. The AMP-hydrogels showed high antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, methicillin-resistant S. aureus (MRSA), and multidrug-resistant Escherichia coli for up to 24 h. Furthermore, the AMP-hydrogels did not present any toxicity to human fibroblasts. The AMPs retained their antimicrobial activity up to 48 h in human blood serum, which is a significant increase in stability compared to when used in dissolved state. A pilot in vivo rat model showed 10-100x less viable counts of S. aureus on AMP-hydrogels compared with control hydrogels during the first 3 days of infection. Studies performed on human whole blood showed that blood coagulated more readily in the presence of AMP-hydrogels as compared to hydrogels without AMPs, indicating potential hemostatic activity. Overall, the results suggest that the combination of amphiphilic hydrogels with covalently bonded AMPs has potential to be used as antibacterial wound dressing material to reduce infections and promote hemostatic activity as an alternative to antibiotics or other antimicrobial agents, whose use should be restricted.
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  • Bartkowska, Aleksandra, et al. (author)
  • Accelerated biodegradation of FeMn porous alloy coated with ZnO: Effect on cytocompatibility and antibiofilm properties
  • 2023
  • In: Surface and Coatings Technology. - 0257-8972. ; 471
  • Journal article (peer-reviewed)abstract
    • Fe-based alloys are being studied as potential candidates for biodegradable implants; however, their degradation rates remain too slow. To accelerate biodegradation while simultaneously hindering biofilm formation, a ZnO coating was deposited onto porous equiatomic FeMn alloy discs by sol-gel method using dip coating. The effect of the ZnO coating on the microstructure, biodegradability, cytocompatibility, and antibacterial properties were investigated. Biodegradability experiments were performed by immersing the specimens in Hank's balanced salt solution and measuring ion release after up to 28 days of immersion. The experiments showed an increased degradation of the FeMn/ZnO sample due to Fe segregation towards the grain boundaries, formation of iron-manganese oxide, and limited formation of degradation products on ZnO. Further, indirect Saos-2 cell cytotoxicity testing in 24 h sample-conditioned media showed no significant cytotoxicity in concentrations equal to or below 50 %. In addition, the total biofilm biovolume formed by Staphylococcus aureus on the FeMn/ZnO surface was significantly reduced compared to the uncoated FeMn. Taken together, these results show that the ZnO coating on FeMn improves the degradation rate, maintains cytocompatibility, and reduces biofilm accumulation when compared to an uncoated FeMn alloy.
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  • Bartkowska, Aleksandra, et al. (author)
  • Biodegradable porous FeMn(-xAg) alloys: assessment of cytocompatibility, mechanical, magnetic and antibiofilm properties
  • 2023
  • In: Materials Advances. - : Royal Society of Chemistry (RSC). - 2633-5409. ; 4:2, s. 616-630
  • Journal article (peer-reviewed)abstract
    • In this work, porous FeMn(-xAg) alloys are fabricated through powder metallurgy methods. The effects of porosity and Ag addition on the microstructure, biodegradability, magnetic and mechanical properties of the alloys are investigated. Studies on the cytocompatibility, inflammatory cytokine response and antibacterial effect are also conducted. The fabricated alloys exhibit a macro- and nanoporous structure, with uniformly distributed silver particles. The biodegradability tests reveal that the release of Mn to the Hank's solution is higher than that of Fe, without significant differences between the alloys. The degradation products consist mainly of Fe, Mn, O and compounds enriched in Ca, P and Cl. As-sintered alloys show a low saturation magnetization value (below 1 emu g−1), which does not increase significantly with immersion time. The results on biocompatibility indicate that all tested alloys are non-cytotoxic, but the addition of Ag might interfere with cell proliferation. However, the ions released by the FeMn(-xAg) alloys do not induce an inflammatory response in macrophages. The obtained results on microbiological interactions reveal that although no significant bactericidal effect is observed at 4 h between FeMn control and FeMn-5Ag, a significant reduction in the total biofilm biomass of both live and dead bacteria is observed after 24 h in Ag containing FeMn-5Ag surfaces.
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  • Calon, T. G. A., et al. (author)
  • Microbiome on the Bone-Anchored Hearing System: A Prospective Study
  • 2019
  • In: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 10
  • Journal article (peer-reviewed)abstract
    • The bone-anchored hearing system (BAHS) has evolved to a common treatment option for various types of hearing revalidation. The BAHS consists of an implant in the skull that breeches the skin. Soft tissue reactions are a common complication associated with BAHS and are generally poorly understood. This study aims to investigate the influence of BAHS and associated skin reactions around the implant. A total of 45 patients were prospectively followed from implantation up to at least 1 year. Swabs were obtained at baseline, 12 weeks follow-up and during cases of inflammation (Holgers score >= 2). The microbiota was assessed using IS-proTM, a bacterial profiling method based on the interspace region between the 16S-23S rRNA genes. Detection of operational taxonomic units, the Shannon Diversity Index, sample similarity analyses and Partial Least Squares Discriminant Analysis (PLS-DA) were employed. Staphylococcus epidermidis, Streptococcus pneumoniae/mitis, Propionibacterium acnes, Staphylococcus capitis, Staphylococcus hominis, Bifidobacterium longum, Haemophilus parainfluenzae, Lactobacillus rhamnosus, Bordetella spp., Streptococcus sanguinis, Peptostreptococcus anaerobius, Staphylococcus aureus, Lactococcus lactis, Enterobacter cloacae, and Citrobacter koseri were the most commonly found bacterial species. S. pneumoniae/mitis was significantly more often observed after implantation, whereas P. acnes was significantly less observed after implantation compared with baseline. The relative abundance of S. epidermidis (17%) and S. aureus (19.4%) was the highest for the group of patients with inflammation. The Shannon Diversity Index was significantly increased after implantation compared with pre-surgical swabs for Firmicutes, Actinobacteria, Fusobacteria, Verrucomicrobia (FAFV), but not for other phyla. When combining all phyla, there was no significant increase in the Shannon Diversity Index. The diversity index was similar post-surgically for patients experiencing inflammation and for patients without inflammation. With a supervised classifier (PLS-DA), patients prone to inflammation could be identified at baseline with an accuracy of 91.7%. In addition, PLS-DA could classify post-surgical abutments as non-inflamed or inflamed with an accuracy of 97.7%. This study shows the potential of using IS-proTM to describe and quantify the microbiota associated with the percutaneous BAHS. Furthermore, the results indicate the possibility of an early identification of patients susceptible to adverse skin reaction following implantation. Both S. aureus and S. epidermidis should be considered as relevant bacteria for BAHS-associated inflammation.
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  • Engstrand, Thomas, et al. (author)
  • Bioceramic Implant Induces Bone Healing of Cranial Defects.
  • 2015
  • In: Plastic and reconstructive surgery. Global open. - : LIPPINCOTT WILLIAMS & WILKINS. - 2169-7574. ; 3:8
  • Journal article (peer-reviewed)abstract
    • Autologous bone or inert alloplastic materials used in cranial reconstructions are techniques that are associated with resorption, infection, and implant exposure. As an alternative, a calcium phosphate-based implant was developed and previously shown to potentially stimulate bone growth. We here uncover evidence of induced bone formation in 2 patients. Histological examination 9 months postoperatively showed multinuclear cells in the central defect zone and bone ingrowth in the bone-implant border zone. An increased expression of bone-associated markers was detected. The other patient was investigated 50 months postoperatively. Histological examination revealed ceramic materials covered by vascularized compact bone. The bone regenerative effect induced by the implant may potentially improve long-term clinical outcome compared with conventional techniques, which needs to be verified in a clinical study.
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  • Gerner, Erik, 1986, et al. (author)
  • Sodium Salicylate Influences the Pseudomonas aeruginosa Biofilm Structure and Susceptibility Towards Silver
  • 2021
  • In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:3
  • Journal article (peer-reviewed)abstract
    • Hard-to-heal wounds are typically infected with biofilm-producing microorganisms, such as Pseudomonas aeruginosa, which strongly contribute to delayed healing. Due to the global challenge of antimicrobial resistance, alternative treatment strategies are needed. Here, we investigated whether inhibition of quorum sensing (QS) by sodium salicylate in different P. aeruginosa strains (QS-competent, QS-mutant, and chronic wound strains) influences biofilm formation and tolerance to silver. Biofilm formation was evaluated in simulated serum-containing wound fluid in the presence or absence of sodium salicylate (NaSa). Biofilms were established using a 3D collagen-based biofilm model, collagen coated glass, and the Calgary biofilm device. Furthermore, the susceptibility of 48-h-old biofilms formed by laboratory and clinical strains in the presence or absence of NaSa towards silver was evaluated by assessing cell viability. Biofilms formed in the presence of NaSa were more susceptible to silver and contained reduced levels of virulence factors associated with biofilm development than those formed in the absence of NaSa. Biofilm aggregates formed by the wild-type but not the QS mutant strain, were smaller and less heterogenous in size when grown in cultures with NaSa compared to control. These data suggest that NaSa, via a reduction of cell aggregation in biofilms, allows the antiseptic to become more readily available to cells.
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  • Gerner, Erik, 1986, et al. (author)
  • Sodium salicylate interferes with quorum-sensing-regulatedvirulence in chronic wound isolates of Pseudomonas aeruginosa in simulated wound fluid
  • 2020
  • In: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 69:5, s. 767-780
  • Journal article (peer-reviewed)abstract
    • Introduction. An important factor for delayed healing of chronic wounds is the presence of bacteria. Quorum sensing (QS), a cell density-dependent signalling system, controls the production of many virulence factors and biofilm formation in Pseudomonas aeruginosa.Aim. Inhibition by sodium salicylate (NaSa) of QS-regulated virulence expression was evaluated in QS-characterized clinical wound isolates of P. aeruginosa, cultured in serum-containing medium.Methodology. Fourteen clinical P. aeruginosa strains from chronic wounds were evaluated for the production of QS signals and virulence factors. Inhibition of QS by NaSa in P. aeruginosa clinical strains, wild-type PAO1 and QS reporter strains was evaluated using in vitro assays for the production of biofilm, pyocyanin, siderophores, alkaline protease, elastase and stapholytic protease.Results. Six clinical strains secreted several QS-associated virulence factors and signal molecules and two were negative for all factors. Sub-inhibitory concentrations of NaSa downregulated the expression of the QS-related genes lasB, rhlA and pqsA and reduced the secretion of several virulence factors in PAO1 and clinical strains cultured in serum. Compared to serum-free media, the presence of serum increased the expression of QS genes and production of siderophores and pyocyanin but decreased biofilm formation.Conclusions.Pseudomonas aeruginosa from chronic wound infections showed different virulence properties. While very few strains showed no QS activity, approximately half were highly virulent and produced QS signals, suggesting that the targeting of QS is a viable and relevant strategy for infection control. NaSa showed activity as a QS-inhibitor by lowering the virulence phenotypes and QS signals at both transcriptional and extracellular levels.
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  • Gerner, Erik, 1986, et al. (author)
  • Targeting Pseudomonas aeruginosa quorum sensing with sodium salicylate modulates immune responses in vitro and in vivo.
  • 2023
  • In: Frontiers in cellular and infection microbiology. - 2235-2988. ; 13
  • Journal article (peer-reviewed)abstract
    • Chronic infections are a major clinical challenge in hard-to-heal wounds and implanted devices. Pseudomonas aeruginosa is a common causative pathogen that produces numerous virulence factors. Due to the increasing problem of antibiotic resistance, new alternative treatment strategies are needed. Quorum sensing (QS) is a bacterial communication system that regulates virulence and dampens inflammation, promoting bacterial survival. QS inhibition is a potent strategy to reduce bacterial virulence and alleviate the negative impact on host immune response.This study investigates how secreted factors from P. aeruginosa PAO1, cultured in the presence or absence of the QS inhibitor sodium salicylate (NaSa), influence host immune response.In vitro, THP-1 macrophages and neutrophil-like HL-60 cells were used. In vivo, discs of titanium were implanted in a subcutaneous rat model with local administration of P. aeruginosa culture supernatants. The host immune response to virulence factors contained in culture supernatants (+/-NaSa) was characterized through cell viability, migration, phagocytosis, gene expression, cytokine secretion, and histology.In vitro, P. aeruginosa supernatants from NaSa-containing cultures significantly increased THP-1 phagocytosis and HL-60 cell migration compared with untreated supernatants (-NaSa). Stimulation with NaSa-treated supernatants in vivo resulted in: (i) significantly increased immune cell infiltration and cell attachment to titanium discs; (ii) increased gene expression of IL-8, IL-10, ARG1, and iNOS, and (iii) increased GRO-α protein secretion and decreased IL-1β, IL-6, and IL-1α secretion, as compared with untreated supernatants.In conclusion, treating P. aeruginosa with NaSa reduces the production of virulence factors and modulates major immune events, such as promoting phagocytosis and cell migration, and decreasing the secretion of several pro-inflammatory cytokines.
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  • Johansson, Martin L, et al. (author)
  • Clinical retrieval and analysis of percutaneous bone-anchored hearing implants using multiple analytical methodologies
  • 2020
  • In: 11TH WORLD BIOMATERIALS CONGRESS 11 - 15 December 2020.
  • Conference paper (other academic/artistic)abstract
    • Introduction: The percutaneous bone-anchored hearing system (BAHS) is an established form of hearing treatment for conductive or mixed hearing loss and single sided deafness [1]. The system consists of a titanium implant inserted in the temporal bone and mounted with an abutment onto which a sound processor is attached. It is considered to be a successful treatment with generally good outcomes in terms of audiology and quality of life [2]. However, associated adverse outcomes, such as peri-abutment inflammation and infection, pain and numbness may necessitate intervention, device removal or implant loss [2, 3]. The clinician must rely on subjective clinical measurements, whereas information on the biological events at the tissue-BAHS interface remain inaccessible. Reports of analyses of planned, electively retrieved BAHS implants, performed under perfectly controlled circumstances, are rare [4, 5]. The aim with this study was to gain insight into the biological processes around percutaneous bone-conducting devices by analysing retrieved implants. Experimental methods: Through the establishment of a bilateral collaboration network with European clinics, a retrieval and analytical protocol have been implemented. This will allow correlation of the clinical data with the underpinning microbiological, molecular and morphological fingerprints at the tissue interface. Multiple analytical and correlative strategies have been used, enabling multiscale and multimodal investigation of the tissue interface. Different sampling procedures and analytical tools were employed, including X-ray micro-computed tomography (micro-CT), histology/histomorphometry, fluorescence in situ hybridization (FISH), microbiology, quantitative polymerase chain reaction (qPCR), backscattered electron scanning electron microscopy (BSE-SEM) and Raman spectroscopy. Results and discussions: So far, retrieval, preservation and investigation of six BAHS implants with surrounding tissue have been performed. Causes for removal (1-7 years after implantation) were chronic pain, recurrent inflammation, cancer and mechanical complications. After micro-CT analysis and the samples were embedded for histological and ultrastructural analyses. This presentation describes the sample preparation route allowing assessment of the different hierarchical levels of interest of the tissue interface. Examples of the results from the different analyses will be presented, with emphasis on correlating the clinical outcome with the analytical findings. Conclusions: The implementation of a retrieval protocol combined with a subsequent multi-scale analytical strategy enables a correlation between the clinical history of patients and the underpinning microbiological, molecular and morphological events in the tissues interfacing the electively removed or failed percutaneous bone-anchored hearing implants.
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  • Johansson, Martin L, et al. (author)
  • Multimodal Analysis of the Tissue Response to a Bone-Anchored Hearing Implant: Presentation of a Two-Year Case Report of a Patient With Recurrent Pain, Inflammation, and Infection, Including a Systematic Literature Review.
  • 2021
  • In: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 11
  • Journal article (peer-reviewed)abstract
    • Osseointegration is a well-established concept used in applications including the percutaneous Bone-Anchored Hearing System (BAHS) and auricular rehabilitation. To date, few retrieved implants have been described. A systematic review including cases where percutaneous bone-anchored implants inserted in the temporal bone were retrieved and analyzed was performed. We also present the case of a patient who received a BAHS for mixed hearing loss. After the initial surgery, several episodes of soft tissue inflammation accompanied by pain were observed, leading to elective abutment removal 14 months post-surgery. Two years post-implantation, the implant was removed due to pain and subjected to a multiscale and multimodal analysis: microbial DNA using molecular fingerprinting, gene expression using quantitative real-time polymerase chain reaction (qPCR), X-ray microcomputed tomography (micro-CT), histology, histomorphometry, backscattered scanning electron microscopy (BSE-SEM), Raman spectroscopy, and fluorescence in situ hybridization (FISH). Evidence of osseointegration was provided via micro-CT, histology, BSE-SEM, and Raman spectroscopy. Polymicrobial colonization in the periabutment area and on the implant, including that with Staphylococcus aureus and Staphylococcus epidermidis, was determined using a molecular analysis via a 16S-23S rDNA interspace [IS]-region-based profiling method (IS-Pro). The histology suggested bacterial colonization in the skin and in the peri-implant bone. FISH confirmed the localization of S. aureus and coagulase-negative staphylococci in the skin. Ten articles (54 implants, 47 patients) met the inclusion criteria for the literature search. The analyzed samples were either BAHS (35 implants) or bone-anchored aural epitheses (19 implants) in situ between 2 weeks and 8years. Themainreasons for elective removal were nonuse/changes in treatment, pain, or skin reactions. Most samples were evaluated using histology, demonstrating osseointegration, but with the absence of bone under the implants' proximal flange. Taken together, the literature and this case report show clear evidence of osseointegration, despite prominent complications. Nevertheless, despite implant osseointegration, chronic pain related to the BAHS may be associated with a chronic bacterial infection and raised inflammatory response in the absence of macroscopic signs of infection. It is suggested that a multimodal analysis of peri-implant health provides possibilities for device improvements and to guide diagnostic and therapeutic strategies to alleviate the impact of complications.
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  • Johansson, Martin L, et al. (author)
  • Non-invasive sampling procedure revealing the molecular events at different abutments of bone-anchored hearing systems–A prospective clinical pilot study
  • 2022
  • In: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 16
  • Journal article (peer-reviewed)abstract
    • Purpose: To investigate the molecular activities in different compartments around the bone-anchored hearing system (BAHS) with either electropolished or machined abutments and to correlate these activities with clinical and microbiological findings. Materials and methods: Twelve patients received machined or electropolished abutments after implant installation of BAHS. Peri-abutment fluid and tissue were collected from baseline to 12 months. Gene expression of cytokines and factors related to tissue healing and inflammation, regeneration and remodelling, as well as bacterial recognition were determined using quantitative-polymerase chain reaction (qPCR). The clinical status was evaluated using the Holgers scoring system, and bacterial colonisation was investigated by culturing. Results: The gene expression of inflammatory cytokines (IL-8, IL-1β, and IL-10) and bacteria-related Toll-like receptors (2 and 4) was higher in the peri-abutment fluid than at baseline and in the peri-abutment tissue at 3 and 12 months. Conversely, the expression of genes related to tissue regeneration (Coll1a1 and FOXO1) was higher in the tissue samples than in the peri-abutment fluid at 3 and 12 months. Electropolished abutments triggered higher expression of inflammatory cytokines (IL-8 and IL-1β) (in peri-abutment fluid) and regeneration factor FOXO1 (in peri-abutment tissue) than machined abutments. Several cytokine genes in the peri-abutment fluid correlated positively with the detection of aerobes, anaerobes and Staphylococcus species, as well as with high Holger scores. Conclusion: This study provides unprecedented molecular information on the biological processes of BAHS. Despite being apparently healed, the peri-abutment fluid harbours prolonged inflammatory activity in conjunction with the presence of different bacterial species. An electropolished abutment surface appears to be associated with stronger proinflammatory activity than that with a machined surface. The analysis of the peri-abutment fluid deserves further verification as a non-invasive sampling and diagnostic procedure of BAHS.
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  • Johansson, Martin L, et al. (author)
  • The microbiological profile of the bone-anchored hearing system.
  • 2019
  • In: 7th International Symposium on Bone Conduction Hearing and Related Technologies (OSSEO), At Miami beach, FL, USA.
  • Conference paper (other academic/artistic)abstract
    • Purpose The aim of this study was to evaluate methods for bacterial sampling and to acquire insight into the role of the microbiota on the clinical outcome of BAHS. Methods and Materials For the identification and quantification of colonising bacteria, 3 sampling techniques from 3 different compartments were evaluated: (i) retrieval of abutments, (ii) sampling of the peri-abutment exudate using paper-points and, (iii) sampling of the peri-abutment soft tissue using a biopsy punch. Results Quantification of viable bacteria was possible from all three compartments. At baseline the soft tissue was mainly colonised by anaerobic bacteria. Anaerobic bacteria and Staphylococcus spp. were subsequently detected in all three compartments at 3 and 12 months. During the one-year follow-up, the common skin coloniser Staphylococcus epidermidis was present at the implant site in most patients whereas Staphylococcus aureus was present in half of the patients. Several associations between clinical and microbiological parameters were found. Conclusion This study confirmed a suitable study design, sampling and analytical methodology to quantitate, describe and isolate the bacterial species associated to BAHS. Characterising the microbiota present at different sites surrounding BAHS as well as elucidating their associations with clinical parameters and host response markers may have relevance for the outcome following implantation.
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  • Juhlin, Annika, et al. (author)
  • Staphylococcal biofilm gene expression on biomaterials - A methodological study
  • 2017
  • In: Journal of Biomedical Materials Research Part A. - : Wiley. - 1549-3296. ; 105:12, s. 3400-3412
  • Journal article (peer-reviewed)abstract
    • The combination of increased healthcare access, universal aging, and infallible therapy demands, synergistically drive the need for the development of biomaterial technologies that mitigate the challenge of biomaterial-associated infections (BAI). Staphylococcus epidermidis and Staphylococcus aureus account for the majority of BAI due to their ability to accumulate in adherent multilayered biofilm. This investigation details the development of gene expression assays to evaluate the genetic processes of attachment, accumulation, maturation, and dispersal phases of biofilms on biomaterials in vitro, while abiding by the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. The biofilm formation of S. epidermidis on polyurethane (PU) central venous catheters and S. aureus on machined titanium (Ti) was examined in terms of gene expression at early and late time points. The results provided insight into how each stage of biofilm formation is orchestrated over time on these biomaterials in vitro. Furthermore, the results suggested that mechanical RNA extraction, organic solvents, elimination of genomic DNA, and preamplification are advisable strategies to implement for biofilm gene expression analysis. It is concluded that this method can be employed for the assessment of biofilm-biomaterial interactions at the molecular level. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3400-3412, 2017.
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  • Morales-Laverde, L., et al. (author)
  • Experimental Polymorphism Survey in Intergenic Regions of the icaADBCR Locus in Staphylococcus aureus Isolates from Periprosthetic Joint Infections
  • 2022
  • In: Microorganisms. - : MDPI AG. - 2076-2607. ; 10:3
  • Journal article (peer-reviewed)abstract
    • Staphylococcus aureus is a leading cause of prosthetic joint infections (PJI) characterized by bacterial biofilm formation and recalcitrance to immune-mediated clearance and antibiotics. The molecular events behind PJI infection are yet to be unraveled. In this sense, identification of polymorphisms in bacterial genomes may help to establish associations between sequence variants and the ability of S. aureus to cause PJI. Here, we report an experimental nucleotide-level survey specifically aimed at the intergenic regions (IGRs) of the icaADBCR locus, which is responsible for the synthesis of the biofilm exopolysaccharide PIA/PNAG, in a collection of strains sampled from PJI and wounds. IGRs of the icaADBCR locus were highly conserved and no PJI-specific SNPs were found. Moreover, polymorphisms in these IGRs did not significantly affect transcription of the icaADBC operon under in vitro laboratory conditions. In contrast, an SNP within the icaR coding region, resulting in a V176E change in the transcriptional repressor IcaR, led to a significant increase in icaADBC operon transcription and PIA/PNAG production and a reduction in S. aureus virulence in a Galleria mellonella infection model. In conclusion, SNPs in icaADBCR IGRs of S. aureus isolates from PJI are not associated with icaADBC expression, PIA/PNAG production and adaptation to PJI.
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  • Morales-Laverde, L., et al. (author)
  • Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic infections
  • 2022
  • In: Biofilm. - : Elsevier BV. - 2590-2075. ; 4
  • Journal article (peer-reviewed)abstract
    • Staphylococcus aureus is a leading cause of prosthetic joint infections (PJI). Surface adhesins play an important role in the primary attachment to plasma proteins that coat the surface of prosthetic devices after implantation. Previous efforts to identify a genetic component of the bacterium that confers an enhanced capacity to cause PJI have focused on gene content, kmers, or single-nucleotide polymorphisms (SNPs) in coding sequences. Here, using a collection of S. aureus strains isolated from PJI and wounds, we investigated whether genetic variations in the regulatory region of genes encoding surface adhesins lead to differences in their expression levels and modulate the capacity of S. aureus to colonize implanted prosthetic devices. The data revealed that S. aureus isolates from the same clonal complex (CC) contain a specific pattern of SNPs in the regulatory region of genes encoding surface adhesins. As a consequence, each clonal lineage shows a specific profile of surface proteins expression. Co-infection experiments with representative isolates of the most prevalent CCs demonstrated that some lineages have a higher capacity to colonize implanted catheters in a murine infection model, which correlated with a greater ability to form a biofilm on coated surfaces with plasma proteins. Together, results indicate that differences in the expression level of surface adhesins may modulate the propensity of S. aureus strains to cause PJI. Given the high conservation of surface proteins among staphylococci, our work lays the framework for investigating how diversification at intergenic regulatory regions affects the capacity of S. aureus to colonize the surface of medical implants.
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  • Shah, Furqan A., et al. (author)
  • Commercially pure titanium (cp-Ti) versus titanium alloy (Ti6Al4V) materials as bone anchored implants - Is one truly better than the other?
  • 2016
  • In: Materials science & engineering. C, Materials for biological applications. - : Elsevier BV. - 1873-0191. ; 62, s. 960-6
  • Journal article (peer-reviewed)abstract
    • Commercially pure titanium (cp-Ti) and titanium alloys (typically Ti6Al4V) display excellent corrosion resistance and biocompatibility. Although the chemical composition and topography are considered important, the mechanical properties of the material and the loading conditions in the host have, conventionally, influenced material selection for different clinical applications: predominantly Ti6Al4V in orthopaedics while cp-Ti in dentistry. This paper attempts to address three important questions: (i) To what extent do the surface properties differ when cp-Ti and Ti6Al4V materials are manufactured with the same processing technique?, (ii) Does bone tissue respond differently to the two materials, and (iii) Do bacteria responsible for causing biomaterial-associated infections respond differently to the two materials? It is concluded that: (i) Machined cp-Ti and Ti6Al4V exhibit similar surface morphology, topography, phase composition and chemistry, (ii) Under experimental conditions, cp-Ti and Ti6Al4V demonstrate similar osseointegration and biomechanical anchorage, and (iii) Experiments in vitro fail to disclose differences between cp-Ti and Ti6Al4V to harbour Staphylococcus epidermidis growth. No clinical comparative studies exist which could determine if long-term, clinical differences exist between the two types of bulk materials. It is debatable whether cp-Ti or Ti6Al4V exhibit superiority over the other, and further comparative studies, particularly in a clinical setting, are required.
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36.
  • Stenlund, Patrik, et al. (author)
  • Effect of load on the bone around bone-anchored amputation prostheses
  • 2017
  • In: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 35:5, s. 1113-1122
  • Journal article (peer-reviewed)abstract
    • Osseointegrated transfemoral amputation prostheses have proven successful as an alternative method to the conventional socket-type prostheses. The method improves prosthetic use and thus increases the demands imposed on the bone-implant system. The hypothesis of the present study was that the loads applied to the bone-anchored implant system of amputees would result in locations of high stress and strain transfer to the bone tissue and thus contribute to complications such as unfavourable bone remodeling and/or elevated inflammatory response and/or compromised sealing function at the tissue-abutment interface. In the study, site-specific loading measurements were made on amputees and used as input data in finite element analyses to predict the stress and strain distribution in the bone tissue. Furthermore, a tissue sample retrieved from a patient undergoing implant revision was characterized in order to evaluate the long-term tissue response around the abutment. Within the limit of the evaluated bone properties in the present experiments, it is concluded that the loads applied to the implant system may compromise the sealing function between the bone and the abutment, contributing to resorption of the bone in direct contact with the abutment at the most distal end. This was supported by observations in the retrieved clinical sample of bone resorption and the formation of a soft tissue lining along the abutment interface. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1113–1122, 2017.
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37.
  • Svensson Malchau, Karin, et al. (author)
  • Biofilm properties in relation to treatment outcome in patients with first-time periprosthetic hip or knee joint infection
  • 2021
  • In: Journal of Orthopaedic Translation. - : Elsevier BV. - 2214-031X. ; 30, s. 31-40
  • Journal article (peer-reviewed)abstract
    • Background: Periprosthetic joint infections (PJI) are challenging complications following arthroplasty. Staphylococci are a frequent cause of PJI and known biofilm producers. Biofilm formation decreases antimicrobial susceptibility, thereby challenging favourable treatment outcomes. The aims of this study were to characterize the biofilm abilities and antimicrobial susceptibilities of staphylococci causing first-time PJI and correlate them to clinical outcome (infection resolution and recurrence). Methods: Reoperations for PJI of the hip or knee between 1st January 2012 to 30th June 2015 performed at the Sahlgrenska University Hospital were identified in a local database. Medical records were reviewed and clinical parameters recorded for patients whose intraoperative bacterial isolates had been stored at the clinical laboratory. Staphylococcal strains isolated from reoperations due to first-time PJI were characterised by their ability to form biofilms using the microtiter plate test. Antimicrobial susceptibility of the strains was determined by minimum inhibitory concentration (MIC) when grown planktonically, and by minimum biofilm eradication concentration (MBEC) when grown as biofilms. MBEC determination was conducted using the Calgary biofilm device (CBD) and a custom-made antimicrobial susceptibility plate containing eight clinically relevant antimicrobial agents. Results: The study group included 49 patients (70 bacterial strains) from first-time PJI, whereof 24 (49%) patients had recurrent infection. Strong biofilm production was significantly associated with recurrent infection. Patients infected with strong biofilm producers had a five-fold increased risk for recurrent infection. Strains grown as biofilms were over 8000 times more resistant to antimicrobial agents compared to planktonic cultures. Biofilms were more susceptible to rifampicin compared to other antimicrobials in the assay. Increased biofilm susceptibility (MBEC > MIC) was observed for the majority of the bacterial strains and antimicrobial agents. Conclusions: Strong biofilm production was significantly associated with increased antimicrobial resistance and PJI recurrence. This underscores the importance of determining biofilm production and susceptibility as part of routine diagnostics in PJI. Strong staphylococcal biofilm production may have implications on therapeutic choices and suggest more extensive surgery. Furthermore, despite the increased biofilm resistance to rifampicin, results from this study support its use in staphylococcal PJI. The Translational Potential of this Article: Like for many biomaterial-associated infections, staphylococci are a common cause of PJI. Their ability to adhere to surfaces and produce biofilms on medical devices is proposed to play a role. However, clinical studies where biofilm properties are directly linked to patient outcome are scarce. This study demonstrates that the majority of staphylococci isolated from first-time PJI were biofilm producers with increased antimicrobial resistance. Patients suffering an infection caused by a staphylococcal strain with strong biofilm production ability had a five-fold greater risk of recurrent infection. This novel finding suggests the importance of evaluating biofilm production as a diagnostic procedure for the guidance of treatment decisions in PJI.
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38.
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39.
  • Svensson, Sara, 1981, et al. (author)
  • A novel soft tissue model for biomaterial-associated infection and inflammation - Bacteriological, morphological and molecular observations
  • 2015
  • In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 41, s. 106-121
  • Journal article (peer-reviewed)abstract
    • Infection constitutes a major risk for implant failure, but the reasons why biomaterial sites are more vulnerable than normal tissue are not fully elucidated. In this study, a soft tissue infection model was developed, allowing the analysis of cellular and molecular responses in each of the sub-compartments of the implant-tissue interface (on the implant surface, in the surrounding exudate and in the tissue). Smooth and nanostructured titanium disks with or without noble metal chemistry (silver, gold, palladium), and sham sites, were inoculated with Staphylococcus epidermidis and analysed with respect to number of viable bacteria, number, viability and gene expression of host cells, and using different morphological techniques after 4 h, 24 h and 72 h. Non-infected rats were controls. Results showed a transient inflammatory response at control sites, whereas bacterial administration resulted in higher recruitment of inflammatory cells (mainly polymorphonuclear), higher, continuous cell death and higher gene expression of tumour necrosis factor-alpha, interleukin-6, interleukin-8, Toll-like receptor 2 and elastase. At all time points, S. epidermidis was predominantly located in the interface zone, extra- and intracellularly, and lower levels were detected on the implants compared with surrounding exudate. This model allows detailed analysis of early events in inflammation and infection associated to biomaterials in vivo leading to insights into host defence mechanisms in biomaterial-associated infections.
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40.
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41.
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42.
  • Svensson, Sara, 1981, et al. (author)
  • Osseointegration of titanium with an antimicrobial nanostructured noble metal coating
  • 2013
  • In: Nanomedicine: Nanotechnology, Biology, and Medicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 9:7, s. 1048-1056
  • Journal article (peer-reviewed)abstract
    • Nanometer scale surface features on implants and prostheses can potentially be used to enhance osseointegration and may also add further functionalities, such as infection resistance, to the implant. In this study, a nanostructured noble metal coating consisting of palladium, gold and silver, never previously used in bone applications, was applied to machined titanium screws to evaluate osseointegration after 6 and 12. weeks in rabbit tibiae and femurs. Infection resistance was confirmed by in vitro adhesion test. A qualitatively and quantitatively similar in vivo bone response was observed for the coated and uncoated control screws, using histology, histomorphometry and electron microscopy. The bone-implant interface analysis revealed an extensive bone formation and direct bone-implant contact. These results demonstrate that the nanostructured noble metal coating with antimicrobial properties promotes osseointegration and may therefore be used to add extra implant functionality in the form of increased resistance to infection without the use of antibiotics. From the Clinical Editor: The authors of this paper demonstrate that nanostructured noble metal coating of implants and prostheses used in orthopedic procedures promotes osseointegration and may be used to add extra implant functionality in the form of increased resistance to infection without the use of antibiotics.
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43.
  • Svensson, Sara, 1981, et al. (author)
  • Role of nanostructured gold surfaces on monocyte activation and Staphylococcus epidermidis biofilm formation.
  • 2014
  • In: International journal of nanomedicine. - 1178-2013 .- 1176-9114. ; 9:1, s. 775-794
  • Journal article (peer-reviewed)abstract
    • The role of material surface properties in the direct interaction with bacteria and the indirect route via host defense cells is not fully understood. Recently, it was suggested that nanostructured implant surfaces possess antimicrobial properties. In the current study, the adhesion and biofilm formation of Staphylococcus epidermidis and human monocyte adhesion and activation were studied separately and in coculture in different in vitro models using smooth gold and well-defined nanostructured gold surfaces. Two polystyrene surfaces were used as controls in the monocyte experiments. Fluorescent viability staining demonstrated a reduction in the viability of S. epidermidis close to the nanostructured gold surface, whereas the smooth gold correlated with more live biofilm. The results were supported by scanning electron microscopy observations, showing higher biofilm tower formations and more mature biofilms on smooth gold compared with nanostructured gold. Unstimulated monocytes on the different substrates demonstrated low activation, reduced gene expression of pro- and anti-inflammatory cytokines, and low cytokine secretion. In contrast, stimulation with opsonized zymosan or opsonized live S. epidermidis for 1 hour significantly increased the production of reactive oxygen species, the gene expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10, as well as the secretion of TNF-α, demonstrating the ability of the cells to elicit a response and actively phagocytose prey. In addition, cells cultured on the smooth gold and the nanostructured gold displayed a different adhesion pattern and a more rapid oxidative burst than those cultured on polystyrene upon stimulation. We conclude that S. epidermidis decreased its viability initially when adhering to nanostructured surfaces compared with smooth gold surfaces, especially in the bacterial cell layers closest to the surface. In contrast, material surface properties neither strongly promoted nor attenuated the activity of monocytes when exposed to zymosan particles or S. epidermidis.
  •  
44.
  • Svensson, Sara, 1981, et al. (author)
  • Site-specific gene expression analysis of implant-near cells in a soft tissue infection model - Application of laser microdissection to study biomaterial-associated infection
  • 2017
  • In: Journal of Biomedical Materials Research Part A. - : Wiley. - 1549-3296. ; 105:8, s. 2210-2217
  • Journal article (peer-reviewed)abstract
    • Analysis of the implant-tissue interface is important for an understanding of the cellular response to biomaterials with different surface characteristics. However, inaccessibility to the site has restricted the detailed evaluation of the tissue surrounding the implant. Laser microdissection enables the isolation of specific cells and tissues for subsequent DNA, RNA, or protein analysis. The present experimental study employed laser microdissection to analyze tissue-specific differences in gene expression in cells around infected or control titanium implants 72 h after subcutaneous implantation in a rat model. Three different tissue zones located 0-800 mu m away from the implant-tissue interface were analyzed. Implant sites challenged with a dose of 10(6) CFU Staphylococcus epidermidis demonstrated higher gene expression of selected markers for inflammation (TNF-alpha, IL-6), cell recruitment (MCP-1, IL-8, IL-8 R), infection (TLR2), and tissue remodeling (MMP-9) compared with control implants. Furthermore, the gene expression analysis of the three extracted tissue zones revealed marked spatial differences, depending on the distance to the implant. Control implants continuously induced higher cell gene expression in the implant-tissue interface compared with cells 200-800 mu m away from the implant, whereas the sites inoculated with S. epidermidis resulted in high gene expression further away from the implant as well. In conclusion, this study demonstrates that laser microdissection is an interesting tool, revealing both gene-and site-specific gene expression patterns in the implant-tissue interface. The technique provides an opportunity for detailed molecular dissection of the biological events related to the implant but occurring at different distances from the implant. (C) 2017 Wiley Periodicals, Inc.
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45.
  • Tillander, Jonatan, 1975, et al. (author)
  • Treatment of periprosthetic joint infections guided by minimum biofilm eradication concentration (MBEC) in addition to minimum inhibitory concentration (MIC): protocol for a prospective randomised clinical trial.
  • 2022
  • In: BMJ open. - : BMJ. - 2044-6055. ; 12:9
  • Journal article (peer-reviewed)abstract
    • Prosthetic joint infections (PJIs) are disastrous complications for patients and costly for healthcare organisations. They may promote bacterial resistance due to the extensive antibiotic use necessary in the PJI treatment. The PJI incidence is estimated to be 1%-3%, but the absolute numbers worldwide are high and increasing as large joint arthroplasties are performed by the millions each year. Current treatment algorithms, based on implant preserving surgery or full revision followed by a semitailored antibiotic regimen for no less than 2-3 months, lead to infection resolution in approximately 60% and 90%, respectively. Antibiotic choice is currently guided by minimum inhibitory concentrations (MICs) of free-living bacteria and not of bacteria in biofilm growth mode. Biofilm assays with relatively rapid output for the determination of minimum biofilm eradication concentrations (MBECs) have previously been developed but their clinical usefulness have not been established.This single-blinded, two-arm randomised study of hip or knee staphylococcal PJI will evaluate 6-week standard of care (MIC guided), or an alternative antibiotic regimen according to an MBEC-guided-based decision algorithm. Sixty-four patients with a first-time PJI treated according to the debridement, antibiotics, and implant retention principle will be enrolled at a single tertiary orthopaedic centre (Sahlgrenska University Hospital). Patients will receive 14 days of standard parenteral antibiotics before entering the comparative study arms. The primary outcome measurement is the proportion of changes in antimicrobial regimen from first-line treatment dependent on randomisation arm. Secondary endpoints are unresolved infection, how microbial properties including biofilm abilities and emerging antimicrobial resistance correlate to infection outcomes, patient reported outcomes and costs with a 12-month follow-up.Approval is received from the Swedish Ethical Review Authority, no 2020-01471 and the Swedish Medical Products Agency, EudraCT, no 2020-003444-80.ClinicalTrials.gov ID: NCT04488458.
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46.
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47.
  • Trobos, Margarita, 1980, et al. (author)
  • Characterization of staphylococcal clinical isolates obtained from the bone-anchored hearing system and relation to clinical outcome
  • 2023
  • In: Materials Advances. - 2633-5409.
  • Conference paper (other academic/artistic)abstract
    • In this work, porous FeMn(-xAg) alloys are fabricated through powder metallurgy methods. The effects of porosity and Ag addition on the microstructure, biodegradability, magnetic and mechanical properties of the alloys are investigated. Studies on the cytocompatibility, inflammatory cytokine response and antibacterial effect are also conducted. The fabricated alloys exhibit a macro- and nanoporous structure, with uniformly distributed silver particles. The biodegradability tests reveal that the release of Mn to the Hank's solution is higher than that of Fe, without significant differences between the alloys. The degradation products consist mainly of Fe, Mn, O and compounds enriched in Ca, P and Cl. As-sintered alloys show a low saturation magnetization value (below 1 emu g−1), which does not increase significantly with immersion time. The results on biocompatibility indicate that all tested alloys are non-cytotoxic, but the addition of Ag might interfere with cell proliferation. However, the ions released by the FeMn(-xAg) alloys do not induce an inflammatory response in macrophages. The obtained results on microbiological interactions reveal that although no significant bactericidal effect is observed at 4 h between FeMn control and FeMn-5Ag, a significant reduction in the total biofilm biomass of both live and dead bacteria is observed after 24 h in Ag containing FeMn-5Ag surfaces.
  •  
48.
  • Trobos, Margarita, 1980, et al. (author)
  • Characterization of sulphonamide-resistant Escherichia coli using comparison of sul2 gene sequences and multilocus sequence typing.
  • 2009
  • In: Microbiology (Reading, England). - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 155:Pt 3, s. 831-836
  • Journal article (peer-reviewed)abstract
    • The sul2 gene encodes sulphonamide resistance (Sul(R)) and is commonly found in Escherichia coli from different hosts. We typed E. coli isolates by multilocus sequence typing (MLST) and compared the results to sequence variation of sul2, in order to investigate the relation to host origin of pathogenic and commensal E. coli strains and to investigate whether transfer of sul2 into different genomic lineages has happened multiple times. Sixty-eight E. coli isolated in Denmark and Norway from different hosts and years were MLST typed and sul2 PCR products were sequenced and compared. PFGE was performed in a subset of isolates. All isolates were divided into 45 different sequence types (STs), with clonal complexes CC10, CC23, CC168, CC350 and CC69 being the most frequent. The sul2 gene from the majority of E. coli strains had only two point mutations, at positions 159 and 197, leading to a synonymous and a non-synonymous change, respectively. Five strains had extra single mutations. All poultry, poultry meat, and Danish human blood isolates had the same sul2 ST and some of these strains clustered under the same MLST STs, indicating that they shared habitats. Most PFGE profiles clustered according to source, but some included different sources. Sul(R) E. coli from different animals, food, human faeces and infections did not cluster according to their origin, suggesting that these habitats share E. coli and sul2 gene types. However, while pig isolates on one occasion clustered with urinary tract infection isolates, poultry isolates seemed more related to isolates from bloodstream infections in humans. Presence of mainly two types of the sul2 gene in both human and animal isolates, irrespective of date and geography, and the presence of both types in the same clonal lineages, suggest horizontal transfer of sul2.
  •  
49.
  • Trobos, Margarita, 1980, et al. (author)
  • Genomics of Staphylococcus aureus and Staphylococcus epidermidis from Periprosthetic Joint Infections and Correlation to Clinical Outcome
  • 2022
  • In: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 10:4
  • Journal article (peer-reviewed)abstract
    • The approach of sequencing or genotyping to characterize the pathogenic potential of staphylococci from orthopedic device-related infection (ODRI) has been applied in recent studies. These studies described the genomic carriage of virulence in clinical strains and compared it with those in commensal strains. Only a few studies have directly correlated genomic profiles to patient outcome and phenotypic virulence properties in periprosthetic joint infections (PJIs). We investigated the association between genomic variations and virulence-associated phenotypes (biofilm-forming ability and antimicrobial resistance) in 111 staphylococcal strains isolated from patients with PJI and the infection outcome (resolved/unresolved). The presence of a strong biofilm phenotype in Staphylococcus aureus and an antibiotic-resistant phenotype in Staphylococcus epidermidis were both associated with treatment failure of PJI. In S. epidermidis, multidrug resistance (MDR) and resistance to rifampicin were associated with unresolved infection. Sequence type 45 (ST45) and ST2 were particularly enriched in S. aureus and S. epidermidis, respectively. S. epidermidis ST2 caused the majority of relapses and was associated with MDR and strong biofilm production, whereas ST215 correlated with MDR and non/weak biofilm production. S. aureus agr II correlated with resolved infection, while S. epidermidis agr I was associated with strong biofilm production and agr III with non/weak production. Collectively, our results highlight the importance of careful genomic and phenotypic characterization to anticipate the probability of the strain causing treatment failure in PJI. Due to the high rate of resistant S. epidermidis strains identified, this study provides evidence that the current recommended treatment of rifampicin and a fluoroquinolone should not be administered without knowledge of the resistance pattern.
  •  
50.
  • Trobos, Margarita, 1980, et al. (author)
  • In vitro evaluation of barrier function against oral bacteria of dense and expanded polytetrafluoroethylene (PTFE) membranes for guided bone regeneration
  • 2018
  • In: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899. ; 20:5, s. 738-748
  • Journal article (peer-reviewed)abstract
    • Aim: This study evaluates biofilm formation and barrier function against Streptococcus oralis of nonresorbable polytetrafluoroethylene (PTFE) guided bone regeneration membranes having expanded (e-PTFE) and dense (d-PTFE) microstructure. Materials and Methods: Three e-PTFE membranes of varying openness, one d-PTFE membrane, and commercially pure titanium discs were evaluated. All e-PTFE membranes consisted of PTFE nodes interconnected by fibrils. The d-PTFE membrane was fibril-free, with large evenly spaced indentations. The surfaces were challenged with S. oralis and incubated statically for 2-48 h. Bacterial colonization, viability, and penetration were evaluated. Results: S. oralis numbers increased over time on all surfaces, as observed using scanning electron microscopy, while cell viability decreased, as measured by colony forming unit (CFU) counting. At 24 h and 48 h, biofilms on d-PTFE were more mature and thicker (tower formations) than on e-PTFE, where fewer layers of cells were distributed mainly horizontally. Biofilms accumulated preferentially within d-PTFE membrane indentations. At 48 h, greater biofilm biomass and number of viable S. oralis were found on d-PTFE compared to e-PTFE membranes. All membranes were impermeable to S. oralis cells. Conclusions: All PTFE membranes were effective barriers against bacterial passage in vitro. However, d-PTFE favored S. oralis biofilm formation.
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