Implant-associated Infections Research Articles

Comparative Genomic Analysis of Cutibacterium spp. Isolates in Implant-Associated Infections.

Bacteria of the genus Cutibacterium are Gram-positive commensals and opportunistic pathogens that represent a major challenge in the diagnosis and treatment of implant-associated infections (IAIs). This study provides insight into the distribution of different sequence types (STs) of C. acnes, and the presence of virulence factors (VFs) in 64 Cutibacterium spp. isolates from suspected or confirmed IAIs obtained during routine microbiological diagnostics. Fifty-three C. acnes, six C. avidum, four C. granulosum, and one C. namnetense isolate, collected from different anatomical sites, were included in our study. Using whole-genome sequencing and a single-locus sequencing typing scheme, we successfully characterized all C. acnes strains and revealed the substantial diversity of STs, with the discovery of six previously unidentified STs. Phylotype IA1, previously associated with both healthy skin microbiome and infections, was the most prevalent, with ST A1 being the most common. Some minor differences in STs' distribution were observed in correlation with anatomical location and association with infection. A genomic analysis of 40 investigated VFs among 64 selected strains showed no significant differences between different STs, anatomical sites, or infection-related and infection undetermined/unlikely groups of strains. Most differences in VF distribution were found between strains of different Cutibacterium spp., subspecies, and phylotypes, with CAMP factors, biofilm-related VFs, lipases, and heat shock proteins identified in all analyzed Cutibacterium spp.

Pharmaceutical applications of chitosan on medical implants: A viable alternative for construction of new biomaterials?

The cytocompatibility, good degradability and antimicrobial action of chitosan (CS) makes this polysaccharide a highly sought after candidate for applications in medical devices. Thus, development of biofunctional implants associated with CS has been proposed in regenerative medicine as these biomaterials can improve and accelerate the osseointegration process on the implants’ surface. The antimicrobial potential of CS has also been investigated in experiments performed on implantable materials associated with CS in different forms, since the incidence of implant-associated infections (IAIs) is increasing worldwide. Biodegradable scaffolds based on CS, and commonly developed as hydrogels, have received lots of attention as implants for controlled release and delivery of drugs. Given this scenario, the present review will focus on methodologies used to coat implant surfaces with CS as well as pharmaceutical applications of these functionalized implants, focusing on cellular, immunological, and antimicrobial responses as well as controlled drug release.

Layer-by-Layer Coatings of Collagen-Hyaluronic acid Loaded with an Antibacterial Manuka Honey Bioactive Compound to Fight Metallic Implant Infections.

Implant-associated severe infections can result in catastrophic implant failures; thus, advanced antibacterial coatings are needed to combat infections. This study focuses on harnessing nature-inspired self-assembly of extracellular matrix (ECM)-like coatings on Ti alloy with a combination of jellyfish-derived collagen (J-COLL) and hyaluronic acid (HA) using our customized automated hybrid layer-by-layer apparatus. To improve the anti-infection efficacy of coatings, we have incorporated a natural antibacterial agent methylglyoxal (MGO, a Manuka honey compound) in optimized multilayer coatings. The obtainment of MGO-loaded multilayer coatings was successfully assessed by profilometry, contact angle, attenuated total reflectance (ATR)-Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. In vitro degradation confirmed the controlled release activity of MGO with a range of concentrations from 0.90 to 2.38 mM up to 21 days. A bacterial cell culture study using Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epidermidis) confirmed that the MGO incorporated within layers 7 and 9 had a favorable effect on preventing bacterial growth and colonization on their surfaces. An in vitro cytocompatibility study confirmed that MGO agents included in the layers did not affect or reduce the cellular functionalities of L929 fibroblasts. In addition, MGO-loaded layers with Immortalized Mesenchymal Stem Cells (Y201 TERT-hMSCs) were found to favor the growth and differentiation of Y201 cells and promote calcium nodule formation. Overall, these surface coatings are promising candidates for delivering antimicrobial activity with bone-inducing functions for future bone tissue engineering applications.

Targeted modulation and enhancement of macrophages via sonodynamic therapy-driven cupferroptosis-like stress for implant-associated biofilm infections

As the vanguard against implant-associated infections (IAIs), macrophages facilitate the phagocytosis and pro-inflammatory polarization of planktonic and biofilm infections, but indirectly serve as a “Trojan horse” for intracellular bacterial infections. Effective drug delivery and macrophage immunomodulation to eliminate intracellular infections will contribute to the treatment of refractory IAIs and prevention of relapse. Herein, we developed an ultrasound-responsive copper-based nanoparticle targeting macrophages by encapsulating copper in a porphyrin metal-organic framework and surface-grafting D-Mannosamine to synthesize CuTCPP@MOF nanodots@ Mannosamine (CTMM) with macrophage-targeting functionality. Concurrent generation of hydroxyl radicals and singlet oxygen in biofilm microenvironment mediated by ultrasound disrupts the biofilm structure, achieving CTMM overload and interfering with bacterial biofilm growth and metabolism. By regulating macrophage oxidative stress metabolism, CTMM induced a cupferroptosis-like stress, characterized by concurrent cuproptosis and ferroptosis, to eliminate intracellular infections. Transcriptomic analysis verified that the cupferroptosis-like stress based on GPX4 axis modulation further promotes macrophage inflammatory activation. This CTMM+US-mediated bacterial clearance in biofilms and macrophage immunomodulation informs the "Trojan War" strategy to combat IAIs clinically.

Flexible and Biocompatible Antifouling Polyurethane Surfaces Incorporating Tethered Antimicrobial Peptides through Click Reactions.

Efficient, simple antibacterial materials to combat implant-associated infections are much in demand. Herein, the development of polyurethanes, both cross-linked thermoset and flexible and versatile thermoplastic, suitable for "click on demand" attachment of antibacterial compounds enabled via incorporation of an alkyne-containing diol monomer in the polymer backbone, is described. By employing different polyolic polytetrahydrofurans, isocyanates, and chain extenders, a robust and flexible material comparable to commercial thermoplastic polyurethane is prepared. A series of short synthetic antimicrobial peptides are designed, synthesized, and covalently attached in a single coupling step to generate a homogenous coating. The lead material is shown to be biocompatible and does not display any toxicity against either mouse fibroblasts or reconstructed human epidermis according to ISO and OECD guidelines. The repelling performance of the peptide-coated materials is illustrated against colonization and biofilm formation by Staphylococcus aureus and Staphylococcus epidermidis on coated plastic films and finally, on coated commercial central venous catheters employing LIVE/DEAD staining, confocal laser scanning microscopy, and bacterial counts. This study presents the successful development of a versatile and scalable polyurethane with the potential for use in the medical field to reduce the impact of bacterial biofilms.

Antibody-antibiotic conjugate targeted therapy for orthopedic implant-associated intracellular S. aureus infections

IntroductionTreating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the ability to invade host cells, enabling it to evade both antibiotics and immune responses during infection, which may result in clinical treatment failures. Therefore, it is critical to identify the host cell type of implant-associated intracellular S. aureus infections and to develop a strategy for highly targeted delivery of antibiotics to the host cells. ObjectivesIntroduced an antibody-antibiotic conjugate (AAC) for the targeted elimination of intracellular S. aureus. MethodsThe AAC comprises of a human monoclonal antibody (M0662) directly recognizes the surface antigen of S. aureus, Staphylococcus protein A, which is conjugated with vancomycin through cathepsin-sensitive linkers that are cleavable in the proteolytic environment of the intracellular phagolysosome. AAC, vancomycin and vancomycin combined with AAC were used in vitro intracellular infection and mice implant infection models. We then tested the effect of AAC in vivo and in vivo by fluorescence imaging, in vivo imaging, bacterial quantitative analysis and bacterial biofilm imaging. ResultsIn vitro, it was observed that AAC captured extracellular S. aureus and co-entered the cells, and subsequently released vancomycin to induce rapid elimination of intracellular S. aureus. In the implant infection model, AAC significantly improved the bactericidal effect of vancomycin. Scanning electron microscopy showed that the application of AAC effectively blocked the formation of bacterial biofilm. Further histochemical and micro-CT analysis showed AAC significantly reduced the level of bone marrow density (BMD) and bone volume fraction (BV/TV) reduction caused by bacterial infection in the distal femur of mice compared to vancomycin treatment alone. ConclusionsThe application of AAC in an implant infection model showed that it significantly improved the bactericidal effects of vancomycin and effectively blocked the formation of bacterial biofilms, without apparent toxicity to the host.

Research progress of phage therapy in orthopedic implant-related infection

The widespread application of implantable materials has brought about a corresponding increase in implant-related complications, with implant-associated infections being the most critical. Biofilms, which often form on these implants, can significantly impede the effectiveness of traditional antibiotic therapies. Therefore, strategies such as surgical removal of infected implants and prolonged antibiotic treatment have been acknowledged as effective measures to eradicate these infections. However,the challenges of antibiotic resistance and biofilm persistence often result in recurrent or hard-to-control infections, posing severe health threats to patients. Recent studies suggest that phages, a type of virus, can directly eliminate pathogenic bacteria and degrade biofilms. Furthermore, clinical trials have demonstrated promising therapeutic results with the combined use of phages and antibiotics. Consequently, this innovative therapy holds significant potential as an effective solution for managing implant-associated infections. This paper rigorously investigates and evaluates the potential value of phage therapy in addressing orthopedic implant-associated infections, based on a comprehensive review of relevant scientific literature.

Antimicrobial approaches for medical implants coating to prevent implants associated infections: Insights to develop durable antimicrobial implants

Advances in implantable technologies results from the rapid improvements in research in the fields of biomedical engineering, biomaterial science, and chemistry. No doubt, implantable technologies have provided greater comfort against several illnesses and diseases; however, pathogens adherence and biofilm formation are still the issues that need to be taken into consideration for further implant modifications. Pathogens colonize implants in a surface-dependent manner, so chances of pathogens' adhesion can be minimized by creating anti-adhesive and antimicrobial surfaces. The ongoing research is focused on the design of appropriate multifunctional coatings with a broad antimicrobial spectrum and high biocompatibility. Antimicrobial peptides in conjugation with polymers, nanoparticles, and other biocompatible agents can be potentially used to develop multifunctional coatings. Antibiotics-based coatings are the ultimate approach; however, optimizing the controlled release of antibiotics will be a breakthrough in this decade. Polymers unveil the extraordinary potential in implant coatings by increasing biocompatibility of coatings, offering the possibility for a triggered release of antimicrobial agents. An in-depth review of effective and biocompatible antimicrobial implant coatings is provided herein. We thoroughly discuss the remarkable antimicrobial agents and their compatibility with the host, including seemingly underexplored stability issues and providing an overlook on different methods of fabrication. The ever-growing materials research field can use this review's highlights to develop multifunctional implant coatings to reduce implant-associated infections.

Prevention of implant-associated spinal infections: the GAID-protocol

Prevention of implant-associated spinal infections: the GAID-protocol

Fracture related Infection - Challenges in definition and diagnosis

In the field of orthopedics and trauma surgery, the rise of periprosthetic joint infections following joint replacement and fracture-related infections (FRI) has become a growing concern. The recent establishment of a definitive definition for FRI aimed to standardize diagnosis and treatment approaches while considering unique aspects of implant-associated infections in the presence of concomitant bone fractures.Diagnosing FRI can be challenging due to the varied clinical symptoms, and confirmatory criteria may not always be evident, necessitating additional diagnostic measures. Blood markers like leukocyte count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) have limited specificity. Although novel biomarkers such as D-dimer and interleukin-6 (IL-6) show potential, they require further investigation. The use of microbiological diagnostics with tissue samples and sonication has improved pathogen detection. Cross-sectional imaging techniques like CT scans and MRI scans help evaluate bone status, soft tissue infiltration, and abscesses. Nuclear medicine techniques are accurate but may not always be practical in routine clinical practice.Histopathological interpretation for FRI remains less standardized compared to periprosthetic joint infections (PJI). FRI diagnosis requires the identification of visible microorganisms in deep tissue specimens and the quantification of polymorphonuclear neutrophils (PMNs).The defined concept of FRI has opened doors for better diagnostic and treatment approaches. However, challenges persist, especially in preoperative diagnosis, particularly for cases with unclear clinical presentations. Future endeavors aimed at optimizing diagnostic procedures and establishing a histopathological classification for FRI could lead to improved treatment recommendations and outcomes.

Identification of a Staphylococcus aureus amidase catalytic domain inhibitor to prevent biofilm formation by sequential virtual screening, molecular dynamics simulation and biological evaluation

Staphylococcus aureus (S. aureus) is one of the common causes of implant associated biofilm infections and their biofilms are resistant to antibiotics. S. aureus amidase (AM) protein, a cell wall hydrolase that cleaves the amide bond between N-acetylmuramic acid and L-alanine residue of the stem peptide, is several fold over-expressed under biofilm conditions. Previous studies demonstrated an autolysin mutant in S. aureus that lacks the AM protein, is highly impaired in biofilm development. We carried out a structure-based small molecule design using the crystal structure of AM protein catalytic domain to identify inhibitors that can block amidase activity and therefore inhibits S. aureus biofilm formation. Sequential virtual screening followed by pharmacokinetic analysis and bioassay studies filtered 25 small molecules from different databases. Two compounds from the SPECS database, SPECS-1 and SPECS-2, were selected based on the best docking score and minimum biofilm inhibitory concentration towards S. aureus biofilms. SPECS-1 and SPECS-2 were further tested for their structural/energetic stability in complex with the AM protein using molecular dynamics simulation and MM-GBSA techniques. In vitro, biofilm inhibition studies on different surfaces confirmed that treatment with SPECS-1 and SPECS-2 at a concentration of 250 μg/ml exhibited significant prevention and disruption of S. aureus biofilms. Finally, the in vitro anti-biofilm activities of these two compounds were validated against Methicillin-resistant S. aureus clinical isolates. We concluded that the discovered compounds SPECS-1 and SPECS-2 are safe and exhibit biofilm preventive and disruption activity for inhibiting the S. aureus biofilms and hence can be used to treat implant-associated biofilm infections.

The microbiome of orthopedic implant-associated infections and its correlation with inflammatory markers

Background: Implant site and periprosthetic joint infections (PPJI) are of major concern with tremendous improvement in orthopedic operative procedures. Early diagnosis of infection is the cornerstone for success rate and prevention of implant failure. The need for inflammatory biomarkers followed by culture sensitivity remains inevitable in the diagnosis of infection. Aims and Objectives: The aim is to study the prevalent biofilm-forming pathogens and to correlate with antimicrobial resistance and also to estimate inflammatory markers to predict the presence of PPJI. Materials and Methods: A descriptive cross-sectional study involving 57 patients showing signs of PPJI was evaluated. Clinical samples of these cases were processed, the bacterial pathogens were isolated and bio-film formation was tested. Inflammatory markers C-reactive protein by latex agglutination and interleukin-6 (IL6) by ELISA is determined. Results: A total of 36 bacterial pathogens are isolated, 17% are Gram-positive cocci (GPC) and 46% are Gram-negative bacilli (GNB). Among these, 54% are biofilm producers and pseudomonas species (33%) are predominant. Antibiotic susceptibility studies showed GPC to be highly sensitive to linezolid (100%) and vancomycin (100%). Among GNB, pseudomonal species showed susceptibility of 85%, 57%, and 47% to meropenem, amikacin, and piperacillin–tazobactam, respectively. Acinetobacter is the most resistant isolate. The IL value of 19.5 arrived by the receiver operating curve showed maximum sensitivity and minimal false positivity. Conclusion: Assessing the infection-specific biomarkers like IL6 levels is advantageous in earlier detection of implant site infection and aid in instituting specific antibiotics for the most common implant and PPJI before permanent implant failure and sepsis.

Long-term antibacterial activity of silver-containing hydroxyapatite coatings against Staphylococcus aureus in vitro and invivo

BackgroundThe potential of silver-containing hydroxyapatite (Ag-HA) coatings to prevent orthopaedic implant-associated infection was explored previously; however, the resistance of Ag-HA coatings to late-onset orthopaedic infections is unknown. This study aimed to evaluate the long-term Ag+ elution and antibacterial properties of the Ag-HA coatings through in vitro and in vivo experiments. MethodsAg-HA-coated disc specimens were immersed in fetal bovine serum (FBS) for six months. Ag concentration was measured over time using inductively coupled plasma-mass spectrometry to evaluate Ag release. The hydroxyapatite (HA)- or Ag-HA-coated disc specimens were immersed in FBS for 3 months to elute Ag+ for in vitro experiments. Methicillin-resistant Staphylococcus aureus (MRSA) suspensions were inoculated onto each disc; after 48 h, the number of colonies and the biofilm volume were measured. HA- or Ag-HA-coated disc specimens were inserted under the skin of Sprague-Dawley rats for three months for in vivo experiments. In in vivo experiment 1, specimens were inoculated with MRSA and the number of colonies was counted after 48 h. In in vivo experiment 2, the specimens were inoculated with bioluminescent S. aureus Xen36 cells, and bioluminescence was measured using an in vivo imaging system. ResultsThe Ag-HA-coated disc specimens continued to elute Ag+ after six months. The biofilm volume in the Ag-HA group was lower than in the HA group. In in vitro and in vivo experiment 1, the bacterial counts in the Ag-HA group were lower than those in the HA group. In in vivo experiment 2, the bioluminescence in the Ag-HA group was lower than that in the HA group on days 1–7 after inoculation. ConclusionsThe Ag-HA-coated discs continued to elute Ag+ for a long period and exhibited antibacterial activity and inhibition of biofilm formation against S. aureus. The Ag-HA coatings have the potential to reduce late-onset orthopaedic implant-associated infections.

Detection of Biofilm Production and Antibiotic Resistance Pattern in Clinical Isolates from Orthopaedic Implants Associated Infections

Introduction: Orthopaedic Implant associated infection is the major problem which leads to implant failure and economic burden to the patient. Implant-associated infections are due to the formation of biofilm at the implantation site leading to multidrug resistant organism. Aim: This study was done to evaluate the causative organisms, their antibiotic sensitivity pattern and their ability to form biofilm over the Implants used in Orthopaedic surgeries. Material and methods: This study was carried out in the department of Microbiology, Adichunchanagiri institute of Medical sciences from September 2019 to August 2022. Swabs from 100 patients who had undergone orthopaedic implant or prosthetic surgery and presented with signs and symptoms of infection were collected and processed as per standard procedures. All the isolates were subjected to detect biofilm production by Congo red agar method, MRSA detection by Cefoxitin disc diffusion test, vancomycin resistant Enterococcus by using Vancomycin (Minimum inhibitory concentration) MIC strips and Extended spectrum β lactamases (ESBL) production by phenotypic confirmatory combined-disc test. Results: Out of the 100 samples processed, culture positivity was observed in 72 specimens. Among them, Staphylococcus aureus 19(26%) was the predominant isolate and 44 (61%) are biofilm producers. 17 (89%) were MRSA (Methicillin resistance Staphylococcus aureus) strains and 15(37%) were ESBL producing strains. Conclusion: The appropriate pre- and post- operative care should be taken to prevent orthopaedic implant associated infections. Staphylococcus spp was the commonest isolate and its ability to produce biofilm indicates the need for an appropriate antibiotic policy and screening for MRSA carriers to reduce the infection. Keywords: Orthopaedic implant, Infection, Biofilm, MRSA, ESBL

Strontium-polydopamine hybrid coating to improve antibacterial ability and osseointegration of titanium implants

Poor osseointegration and implant-associated infection of titanium implants have prompted their urgent development. Strontium (Sr) is widely recognized to promote osteoblast differentiation and inhibit osteoclast growth. To this end, this study aimed to develop a Sr-containing polydopamine (PDA)-coated implant with practical antibacterial ability and excellent osseointegration ability to meet clinical applications. This hybrid coating used PDA as an adhesion layer and a carrier for Sr ions. The effects of Sr contents on shear bond strength, in vitro stability, antibacterial ability, and in vitro osteogenic activity of the implant were evaluated. The Sr-doped PDA surface was soaked in simulated body fluid (SBF) at pH 7.4 or 5.0 for a long time (up to 90 days) to evaluate the in vitro stability. The antimicrobial ability of the hybrid coating against E. coli and S. aureus was examined, while its cellular function was assessed using RAW 264.7 and MG63 cells. The current phase and chemical composition results indicated the presence of Sr ions on the surface of PDA. When Sr was added to PDA, the initial shear strength values were comparable to those of the PDA coating. Soaking time reduced the strength values of Sr-containing coatings, especially for 90 days. However, Sr coating significantly reduced the growth of the two bacteria in a dose-dependent manner. Likewise, Sr coating had a significant dose-dependent inhibitory effect on the development of RAW 264.7 cells but improved MG63 osteogenesis. In conclusion, 40 % Sr-containing PDA hybrid coating on titanium implants may be a potential implant in terms of in vitro stability, antibacterial ability, and osteogenic activity.

Microenvironment-Regulating Drug Delivery Nanoparticles for Treating and Preventing Typical Biofilm-Induced Oral Diseases.

The oral cavity comprises an environment full of microorganisms. Dysregulation of this microbial-cellular microenvironment will lead to a series of oral diseases, such as implant-associated infection caused by Staphylococcus aureus (S. aureus) biofilms and periodontitis initiated by Streptococcus oralis (S. oralis). In this study, a liposome-encapsulated indocyanine green (ICG) and rapamycin drug-delivery nanoparticle (ICG-rapamycin) is designed to treat and prevent two typical biofilm-induced oral diseases by regulating the microbial-cellular microenvironment. ICG-rapamycin elevates the reactive oxygen species (ROS) and temperature levels to facilitate photodynamic and photothermal mechanisms under near-infrared (NIR) laser irradiation for anti-bacteria. In addition, it prevents biofilm formation by promoting bacterial motility with increasing the ATP levels. The nanoparticles modulate the microbial-cellular interaction to reduce cellular inflammation and enhance bacterial clearance, which includes promoting the M2 polarization of macrophages, upregulating the anti-inflammatory factor TGF-β, and enhancing the bacterial phagocytosis of macrophages. Based on these findings, ICG-rapamycin is applied to implant-infected and periodontitis animal models to confirm the effects in vivo. This study demonstrates that ICG-rapamycin can treat and prevent biofilm-induced oral diseases by regulating the microbial-cellular microenvironment, thus providing a promising strategy for future clinical applications.

Management of Biofilm with Breast Implant Surgery.

After studying this article, the participant should be able to: 1. Understand how bacteria negatively impact aesthetic and reconstructive breast implants. 2. Understand how bacteria infect breast implants. 3. Understand the evidence associated with common implant infection-prevention strategies, and their limitations. 4. Understand why implementation of bacteria-mitigation strategies such as antibiotic administration or "no-touch" techniques may not indefinitely prevent breast implant infection. Bacterial infection of aesthetic and reconstructive breast implants is a common and expensive problem. Subacute infections or chronic capsular contractures leading to device explantation are the most commonly documented sequelae. Although bench and translational research underscores the complexities of implant-associated infection, high-quality studies with adequate power, control groups, and duration of follow-up are lacking. Common strategies to minimize infections use antibiotics-administered systemically, in the breast implant pocket, or by directly bathing the implant before insertion-to limit bacterial contamination. Limiting contact between the implant and skin or breast parenchyma represents an additional common strategy. The clinical prevention of breast implant infection is challenged by the clean-contaminated nature of breast parenchyma, and the variable behavior of not only specific bacterial species but also their strains. These factors impact bacterial virulence and antibiotic resistance.

Designing Gallium-Containing Hydroxyapatite Coatings on Low Modulus Beta Ti-45Nb Alloy

Low-modulus β-type Ti-45Nb alloy is a promising implant material due to its good mechanical biocompatibility, non-toxicity, and outstanding corrosion resistance. Its excellent chemical stability brings new challenges to chemical surface modification treatments, which are indispensable for both osteogenesis and antibacterial performance. Coatings containing metal ions as anti-microbial agents can be an effective way to reduce implant-associated infections caused by bacterial biofilm. Gallium ion (Ga3+) has the potential to reduce bacterial viability and biofilm formation on implant surfaces. In this study, a novel two-step process has been proposed for Ga3+ incorporation in hydroxyapatite (HAP) to develop bioactive and antibacterial surfaces on Ti-45Nb alloy. For the generation of bioactive surface states, HAP electrodeposition was conducted, followed by wet chemical immersion treatments in gallium nitrate (1 mM). Different buffers such as phosphate, sodium bicarbonate, ammonium acetate, and citrate were added to the solution to maintain a pH value in the range of 6.5–6.9. Coating morphology and HAP phases were retained after treatment with gallium nitrate, and Ga3+ ion presence on the surface up to 1 wt.% was confirmed. Combining Ga and HAP shows great promise to enable the local delivery of Ga3+ ions and consequent antibacterial protection during bone regeneration, without using growth factors or antibiotics.

2D silicene nanosheets-loaded coating for combating implant-associated infection

Implant-associated infection (IAI) is an unsolved problem in orthopaedics. Current therapies, including antibiotics and surgical debridement, can lead severe clinical and financial burdens on patients. Therefore, there is an urgent need to reinforce the inherent antibacterial properties of implants. Recently, two-dimensional (2D) silicene nanosheets (SNs) have gained increasing attention in biomedical fields owing to their considerable biocompatibility, biodegradability and strong photothermal-conversion performance. Herein, a dual-functional photosensitive coating on a Ti substrate (denoted as TPSNs) was rationally fabricated for bacterial inhibition and osteogenesis promotion. For the first time, SNs were loaded onto the surface of implants. Hyperthermia generated by the SNs and polydopamine (PDA) coating under 808 nm laser irradiation achieved the in vitro anti-bacterial efficiency of 90.7 ± 2.4 % for S. aureus and 88.0 ± 5.8 % for E. coli, respectively. In addition, TPSNs exhibited promising biocompatibility for the promotion of BMSC (bone marrow mesenchymal stem cells) proliferation and spreading. The presence of silicon (Si) in TPSNs contributed to the improved osteogenic differentiation of BMSCs, elevating the expressions of RUNX2 and OCN. In animal experiments, the combination of TPSNs with photothermal therapy (PTT) achieved an anti-bacterial efficiency of 89.2 % ± 1.6 % against S. aureus. Furthermore, TPSNs significantly improved bone-implant osseointegration in vivo. Overall, the development of a dual-functional TPSNs coating provides a new strategy for combating IAI.

Medical titanium surface-modified coatings with antibacterial and anti-adhesive properties for the prevention of implant-associated infections

Implant-associated infections (IAIs) caused by drug-resistant bacteria remain a critical factor in the failure of implant procedures. Therefore, it is urgent to develop an effective anti-infection coating for implant surface modification to prevent IAIs. Herein, an antibacterial and anti-adhesive coating (CMP-Ti) constructed on the surface of titanium implants is reported, formed by the nanomaterial CeO2@Mn3O4 NRs (CM NRs) with antibacterial activity and the superhydrophilic polymer polyethylene glycol (PEG). The nanocatalyst CM NRs on the surface of CMP-Ti induce ferroptosis-like death of bacteria by catalyzing the production of hydroxyl radical (•OH) and singlet oxygen (1O2) and the consumption of glutathione (GSH). The superhydrophilic coating of CMP-Ti can effectively prevent adherence of drug-resistant bacteria and avoid biofilm formation. By combining the “active offense” antibacterial mechanism with the “passive defense” anti-adhesion mechanism, CMP-Ti can kill bacteria and inhibit biofilm formation. The results of in vivo studies showed that CMP-Ti effectively prevented implant-associated infections caused by Methicillin-resistant Staphylococcus aureus (MRSA), thus promoting tissue repair and osseointegration. Therefore, this multifunctional coating combining “active offense” and “passive defense” provides a promising way to prevent IAIs caused by drug-resistant bacteria and to promote tissue repair in the future.