Prevention Of Implant-associated Infections Research Articles

Temperature dependent physicochemical characteristics, antibacterial and cytotoxic potential of iron quantum cluster templated hydroxyapatites

Design and development of novel nanobiomaterials with multifunctional properties hold the promise of new therapeutic strategies to improve the current clinical research in the field of tissue engineering and regenerative medicine. Here, we have successfully synthesized novel autofluorescent hydroxyapatite (HAP) using a template-assisted assembly process followed by a hydrothermal method. Iron quantum cluster (FeQC) were applied as an ideal template for obtaining fluorescent HAP nanorod-assembled microspheres under different hydrothermal temperatures. We evaluated the changes in physicochemical properties, cell viability, and antibacterial activity of HAP microstructures at 120 °C, 150 °C, and 180 °C reaction temperatures. The obtained HAP samples showed an increase in size, a decrease in surface area, and also, a change in the emission wavelength range when the synthesis temperature increases. The cytotoxicity assay results of human amniotic membrane epithelial cells and C2C12 cell line revealed that the HAP with the higher specific surface area show more interaction with cells which lead to higher cytotoxicity effect. The produced HAPs displayed an inhibition zone for Escherichia coli and Staphylococcus aureus bacteria. Therefore, they showed synergistic antibacterial activity against both Gram-negative and Gram-positive bacteria. Our data clearly revealed that the presented biocompatible, multicolor, and highly stable fluorescent HAPs with considerable antibacterial and antioxidant activity have great potential for imaging applications as well as the prevention of implant-associated infections. • A novel fluorescent Hydroxyapatites (HAP) were fabricated at different hydrothermal temperatures. • The fluorescent HAP samples were synthesized using iron quantum cluster as a template. • The produced HAPs exhibited multicolor fluorescence emission. • The Fluorescent HAP samples exhibited cell-type dependence cytotoxic activity. • The synthesized HAPs showed potent antibacterial effect against E.coli and S.aureus bacteria.

The changes made in the article titled “EFFICIENCY OF SILVER-COATED TITANIUM ALLOY SCREWS IN THE PREVENTION OF IMPLANT-ASSOCIATED INFECTIONS” in the original articles section published in JTSS 2021 32(2) are as follows.

The changes made in the article titled “EFFICIENCY OF SILVER-COATED TITANIUM ALLOY SCREWS IN THE PREVENTION OF IMPLANT-ASSOCIATED INFECTIONS” in the original articles section published in JTSS 2021 32(2) are as follows.

Biofunctionalization of selective laser melted porous titanium using silver and zinc nanoparticles to prevent infections by antibiotic-resistant bacteria

Antibiotic-resistant bacteria are frequently involved in implant-associated infections (IAIs), making the treatment of these infections even more challenging. Therefore, multifunctional implant surfaces that simultaneously possess antibacterial activity and induce osseointegration are highly desired in order to prevent IAIs. The incorporation of multiple inorganic antibacterial agents onto the implant surface may aid in generating synergistic antibacterial behavior against a wide microbial spectrum while reducing the occurrence of bacterial resistance. In this study, porous titanium implants synthesized by selective laser melting (SLM) were biofunctionalized with plasma electrolytic oxidation (PEO) using electrolytes based on Ca/P species as well as silver and zinc nanoparticles in ratios from 0 to 100% that were tightly embedded into the growing titanium oxide layer. After the surface bio-functionalization process, silver and zinc ions were released from the implant surfaces for at least 28 days resulting in antibacterial leaching activity against methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, the biofunctionalized implants generated reactive oxygen species, thereby contributing to antibacterial contact-killing. While implant surfaces containing up to 75% silver and 25% zinc nanoparticles fully eradicated both adherent and planktonic bacteria in vitro as well as in an ex vivo experiment performed using murine femora, solely zinc-bearing surfaces did not. The minimum inhibitory and bactericidal concentrations determined for different combinations of both types of ions confirmed the presence of a strong synergistic antibacterial behavior, which could be exploited to reduce the amount of required silver ions by two orders of magnitude (i.e., 120 folds). At the same time, the zinc bearing surfaces enhanced the metabolic activity of pre-osteoblasts after 3, 7, and 11 days. Altogether, implant biofunctionalization by PEO with silver and zinc nanoparticles is a fruitful strategy for the synthesis of multifunctional surfaces on orthopedic implants and the prevention of IAIs caused by antibiotic-resistant bacteria. Statement of SignificanceImplant-associated infections are becoming increasingly challenging to treat due to growing antibiotic resistance against antibiotics. Here, we propose an alternative approach where silver and zinc nanoparticles are simultaneously used for the biofunctionalization of rationally designed additively manufactured porous titanium. This combination of porous design and tailored surface treatment allows us to reduce the amount of required silver nanoparticles by two orders of magnitude, fully eradicate antibiotic-resistant bacteria, and enhance the osteogenic behavior of pre-osteoblasts. We demonstrate that the resulting implants display antibacterial activity in vitro and ex vivo against methicillin-resistant Staphylococcus aureus.

Prevention of Implant-Associated Infection in Neuromodulation: Review of the Literature and Prototype of a Novel Protective Implant Coating.

Background: Implanting hardware into surgical sites increases the rate of infection associated with these sites. Without novel efforts to reduce this rate of infection, we can expect to see an increase in the number of hardware-associated infections as more patients are implanted with these devices. These infections often necessitate the removal of these devices resulting in a significant financial and clinical burden to patients. We developed a prototype antibiotic coating using products that are both low cost and that can be sourced easily. Our study aims to test the effectiveness of this coating against bacteria commonly observed in hospital-associated infections. Methods: The antibiotic coating was prepared by combining one gram of vancomycin and 500 mg of ciprofloxacin in 50 mL of glycerol. The coating was examined for inhibition of growth of Pseudomonas aeruginosa PA14 and Staphylococcus aureus AH2486 and compared with the bacterial growth of the above bacteria in glycerol alone. The growth curves were plotted measuring the bacterial growth at 5 h intervals. Results: The results of the growth curves clearly demonstrate a lack of bacterial growth when these bacteria are combined with glycerol combined with our selected antibiotic agents. Conclusion: There appears to be a limited interest from device companies in developing new strategies for infection prevention associated with neurosurgical hardware, and we propose that this prototype will be an effective and low-cost solution to a large problem.

Synthesis of Hydroxyapatite with Antibacterial Properties Using a Microwave-Assisted Combustion Method

The prevention of implant-associated infections has been increasing clinically in orthopedic surgery. Hydroxyapatite with antibacterial properties was synthesized using a microwave-assisted combustion method. High crystallinity at low temperature can be achieved using this method. The synthesized hydroxyapatite exhibited a superior clear zone for both Gram-positive and Gram-negative bacteria. Electron spin resonance (ESR) and X-ray photoelectron spectroscopy (XPS) were used for the radical investigation. The application of intelligent ink testing and an antioxidant assay using DPPH reduction were also used to confirm the existence of radicals. These techniques provided data confirming that radicals are responsible for the antibacterial properties. The synthesized antibacterial hydroxyapatite would be a good candidate for the prevention any infection with medical implants and injection materials causing failure in bone repair.

Sodium butyrate-modified sulfonated polyetheretherketone modulates macrophage behavior and shows enhanced antibacterial and osteogenic functions during implant-associated infections.

Prevention of implant-associated infections and insufficient bone tissue integration is critical to exploit the immunomodulatory properties and antibacterial effects of implant materials, which have attracted considerable attention. Modulation of the functions of immune cells in different environments is crucial for managing infection and inferior bone integration via immunomodulation. In this work, sodium butyrate, a fermentation product of gut microbiota, was loaded onto 3D porous sulfonated polyetheretherketone (SP) to modulate the immune responses of cells in different environments. Evaluation of in vitro antibacterial effects showed that sodium butyrate-loaded SP exhibited superior antibacterial activity, especially in the samples containing high concentrations of sodium butyrate. Under bacterial stimulation, the phagocytic activity of macrophages increased with an increase in the sodium butyrate concentration via the production of reactive oxygen species (ROS), which favoured bactericidal activity in the implant-associated infection stage. For bacterial elimination, sodium butyrate-containing SP could polarize macrophages to the M2 phenotype and subsequently stimulate anti-inflammatory cytokine secretion, which is considered beneficial for bone regeneration in the tissue repair stage. In vitro osteogenesis was evaluated and the results demonstrated that treatment with sodium butyrate-containing SP increased the expression of osteogenic genes and proteins. An in vivo rat osteomyelitis model was used to evaluate the protective effect of the SP-loaded with sodium butyrate on bone destruction and osteolysis under infection conditions. To study osteogenesis in vivo, a rat femoral model without infection was used. The results indicated that the SP-B2 group exhibited superior anti-infection capacity and induced new bone formation around the implant in vivo. Treatment with sodium butyrate-containing porous SP modulated the macrophage response under different stimuli, thereby serving as a new approach for the design of smart implant materials with superior antibacterial and bone repair properties.

FS: Prevention of implant-associated infections

FS: Prevention of implant-associated infections

Evaluation of free or anchored antimicrobial peptides as candidates for the prevention of orthopaedic device-related infections.

The prevention of implant-associated infection, one the most feared complications in orthopaedic surgery, remains a major clinical challenge and urges development of effective methods to prevent bacterial colonization of implanted devices. Alpha-helical antimicrobial peptides (AMPs) may be promising candidates in this respect due to their potent and broad-spectrum antimicrobial activity, their low tendency to elicit resistance and possible retention of efficacy in the immobilized state. The aim of this study was to evaluate the potential of five different helical AMPs, the cathelicidins BMAP-27 and BMAP-28, their (1-18) fragments and the rationally designed, artificial P19(9/G7) peptide, for the prevention of orthopaedic implant infections. Peptides were effective at micromolar concentrations against 22 Staphylococcus and Streptococcus isolates from orthopaedic infections, while only BMAP-28 and to a lesser extent BMAP-27 were active against Enterococcus faecalis. Peptides in solution showed activities comparable to those of cefazolin and linezolid, on a molar basis, and also a variable capacity to neutralize bacterial lipopolysaccharide, while devoid of adverse effects on MG-63 osteoblast cells at concentrations corresponding to the MIC. The (1-18) BMAP fragments and P19(9/G7) were selected for further examination, based on better selectivity indices, and showed effectiveness in the presence of hyaluronic acid and in synovial fluid, while human serum affected their activity to variable extents, with BMAP-27(1-18) best retaining activity. This peptide was immobilized on streptavidin-resin beads and retained activity against reference Staphylococcus epidermidis and Staphylococcus aureus strains, with negligible toxicity towards osteoblasts, underlining its potential for the development of infection-resistant biomaterials for orthopaedic application. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Nanobiotechnology Perspectives on Prevention and Treatment of Ortho-paedic Implant Associated Infection.

Implants are an inevitable part of orthopaedic surgery. However, implant associated infection remains a major challenge for orthopaedic surgeons and researchers. This review focuses on current options available for prevention of implant associated infection, their drawbacks and future promising applications of nanotechnology-based approaches. Nanobiotechnology has shown remarkable progress in recent years especially in biomaterials, diagnostics, and drug delivery system. Although several applications of nanobiotechnology in orthopaedics have been described, few have elaborated their role in the prevention of implant related infection in orthopaedics. Novel "smart" drug delivery systems that release antibiotics locally in response to stimuli such as pH, temperature, enzymes or antigens; implant surface modification on a nanoscale to inhibit bacterial adhesion and propagation at the surgical site and biological approaches such as gene therapy to neutralize bacterial virulence and biomolecules to inhibit the quorum sensing adhesion of bacteria and disruption of biofilms can be used effectively to prevent orthopaedic implant related bacterial infection.

Macrophage responses to implants: prospects for personalized medicine.

Implants, transplants, and implantable biomedical devices are mainstream solutions for a wide variety of human pathologies. One of the persistent problems around nondegradable metallic and polymeric implants is failure of macrophages to resolve the inflammation and their tendency to stay in a state, named "frustrated phagocytosis." During the initial phase, proinflammatory macrophages induce acute reactions to trauma and foreign materials, whereas tolerogenic anti-inflammatory macrophages control resolution of inflammation and induce the subsequent healing stage. However, implanted materials can induce a mixed pro/anti-inflammatory phenotype, supporting chronic inflammatory reactions accompanied by microbial contamination and resulting in implant failure. Several materials based on natural polymers for improved interaction with host tissue or surfaces that release anti-inflammatory drugs/bioactive agents have been developed for implant coating to reduce implant rejection. However, no definitive, long-term solution to avoid adverse immune responses to the implanted materials is available to date. The prevention of implant-associated infections or chronic inflammation by manipulating the macrophage phenotype is a promising strategy to improve implant acceptance. The immunomodulatory properties of currently available implant coatings need to be improved to develop personalized therapeutic solutions. Human primary macrophages exposed to the implantable materials ex vivo can be used to predict the individual's reactions and allow selection of an optimal coating composition. Our review describes current understanding of the mechanisms of macrophage interactions with implantable materials and outlines the prospects for use of human primary macrophages for diagnostic and therapeutic approaches to personalized implant therapy.

New strategies in the prevention of implant-associated infections

New strategies in the prevention of implant-associated infections