Aim. The utilization of silver as an anti-infective agent is a subject of debate within the scientific community, with recurring discussions surrounding its biocompatibility. Presently, galvanic silver coating finds widespread clinical application in mitigating infection risks associated with large joint arthroplasties. While some instances have linked this coating to sporadic cases of localized argyria, these occurrences have not exhibited systematic or functional limitations. To address concerns regarding biocompatibility, a novel approach has been devised for anti-infective implant coatings: encapsulating silver nitrate within a biopolymer reservoir for non-articulating surfaces. This poly-L-lactic acid layer releases silver ions gradually, thereby circumventing biocompatibility concerns. Method. Female C57BL/6 mice were utilized as an experimental model, with 6x2 mm Ti6Al4V discs, coated with or without the biopolymer-protected silver coating, implanted subcutaneously on both sides of the vertebrae. Daily blood samples were collected, and serum was analyzed for C-reactive protein (CRP) and silver concentration. After three days, histopathological analyses were conducted on the surrounding soft tissue pouch. Results. Maximum CRP levels in the silver group (4.80 mg/L; Median: 3.29 mg/L; IQR: 2.38 to 3.73) did not significantly differ from the control group (4.58 mg/L; Median: 2.93 mg/L; IQR: 1.91 to 3.78) over the study period. Silver levels in serum 24 hours post-implantation were 64 µg/L (IQR: 35 to 78) and decreased subsequently over three days to 23 µg/L (IQR: 13 to 28). Histopathological examinations revealed a similarly strong expression of inflammation signs in tissue samples from the two groups. Conclusions. Despite evidence of local inflammation indicated by CRP and histopathological analysis, no significant difference was observed between the coated and uncoated groups. This suggests that any inflammation may be attributed to the implantation procedure rather than silver influence. Furthermore, silver levels remained below the toxic limit, indicating the efficacy of the biopolymer-protected reservoir in aiding biocompatibility. This study underlines the potential of biopolymer-protected silver reservoirs in enhancing the safety profile of anti-infective silver implant coatings, warranting further investigation into their clinical application

Implant-associated infection is a major source of morbidity in orthopaedic surgery. There has been extensive research into the development of materials that prevent biofilm formation, and hence, reduce the risk of infection. Silver nanoparticle technology is receiving much interest in the field of orthopaedics for its antimicrobial properties, and the results of studies to date are encouraging. Antimicrobial effects have been seen when silver nanoparticles are used in trauma implants, tumour prostheses, bone cement, and also when combined with hydroxyapatite coatings. Although there are promising results with in vitro and in vivo studies, the number of clinical studies remains small. Future studies will be required to explore further the possible side effects associated with silver nanoparticles, to ensure their use in an effective and biocompatible manner. Here we present a review of the current literature relating to the production of nanosilver for medical use, and its orthopaedic applications. Cite this article: Bone Joint J 2015; 97-B:582–9

Introduction. Implant associated infections are responsible for over 10 % of recorded orthopaedic revision surgeries across the UK, with higher infection rates commonly observed for other endoprostheses such as cranioplasties. To prevent colonization and biofilm formation on implant surfaces, the use of silver coatings has shown positive results in clinical setting due to its synergistic function with conventional antibiotic prophylaxes. Additive manufacturing allows manufacture of entirely new implant geometries such as lattice structures to enhance osseointegration, however this limits the ability to uniformly coat implants. Direct integration of silver into the powder feedstock for selective laser melting (SLM) may allow manufacture of a biomedical alloy with innate, long lasting antimicrobial properties without compromising possible geometries and with no coating process necessary. Methods. Feedstock powders of 15–45 micron Grade 5 Ti-64 (Renishaw Plc) and Ag-999 powder (CooksonGold) were characterized using laser particle size analysis, ICP-OES, LECO-ONH, and morphological analysis in SEM. A blend of Ti-64 with 3 wt% Ag-999 powder (Ti-643) was produced by tumble blending, and validated by SEM and EDS. Parameters for manufacture were established using a 17 point design of experiment (DoE) exploring a 2D parameter space of applied laser power and laser scanning speed. Samples were manufactured using a ConceptLaser M2 LaserCusing SLM. Density was assessed by He pycnometry, and cross-sections analysed for defects by optical microscopy. Silver distribution was mapped by micro X-Ray Fluoroscopy (µXRF) and energy-dispersive X-ray spectroscopy (EDS). Optimum parameters were identified and used to manufacture all subsequent samples. Cylindrical Ti-643 samples were manufactured for further physical characterization and bacterial investigation, alongside control Ti-64 samples manufactured using existing optimum parameters. Samples were polished using silicon carbide papers to a 4000-grit surface finish. Contact angle measurements were made by goniometry. Silver elution characteristics were assessed by immersion in water refreshed on a daily basis, and sampled over a 14 day period using ICP-OES. Viability of S. aureus was compared to control samples according to the Japanese standard test method, JIS Z 2801:2000. Results. Across the entire parameter space tested, selective laser melting (SLM) of all 17 samples was successful, with no delamination. An increased recoater blade speed was required to achieve uniform spreading in process versus pure Ti-6Al- 4V powder, indicating an increased cohesivity of the Ti-643 blend. The presence of silver in all samples was confirmed by µXRF, indicating that there was no excessive evaporation of silver in-process. Laser parameters were found to alter the defect density and microstructure scale, though sample density was tightly clustered in a range from 4.415 to 4.453 gcm-3, showing relatively low process variation. No significant difference in bacterial survival was found between control and Ti-643 samples, indicating that further microstructural optimization is needed to guarantee efficacy

Infected mega-endoprostheses are difficult to treat with systemic antibiotics due to encapsulation of the implant by fibrous tissue, formation of biofilms and antibiotic resistant bacteria. Modifying the implant surface by incorporating a bactericidal agent may reduce infection. Infection rates are typically in the range of 8% to 30%. This study describes a novel process method of “stitching-in” ionic silver into the implant surface, in vitro testing and its early clinical usage. A novel process has been developed to “stitch in” ionic silver into the upper surface of titanium alloy (Ti6Al4V). The process produces a modification by anodisation of the titanium alloy in dilute phosphoric acid, followed by absorption of silver from an aqueous solution. The engineered surface modification is therefore integral with the substrate and loaded with silver by an ion exchange reaction. Using this technique the maximum inventory of silver for typical a mega-prosthesis is 6mg and this is greater than 300 times lower than the No Observable Adverse Affects Level (NOAEL). Scanning electron microscopy revealed that the silver was concentrated in pits and forming reservoirs of ionic silver exposed to the body tissues. Laboratory-based studies focusing on the safety and efficacy of silver as a bactericidal agent have included investigation into cytotoxicity using fibroblast and osteoblast cell lines, the impact of silver in reducing corrosion and laboratory testing to establish if the modified surface has an effect on the wear and mechanical characteristics. A range of fatigue, static, tensile pull off tests were performed. The silver elution profiles for both silver loaded and HA coated over a silver loaded surface have been examined. Histological studies were also performed to examine the impact of the silver on osseointegration. The in vitro results confirm that silver is an effective antimicrobial agent. The mechanical characterization studies have identified that the surface treatment has no or minimal impact on the implant surface. Early results of the elution studies are encouraging showing that the HA coating of a silver loaded surface does not “seal” in the silver. To date (May 10) 147 silver treated mega-prostheses have been implanted since March 2006. The majority of implants were distal femoral (29%), proximal tibial (23%) or hemiplevic (10%). The most common indication was revision of a failed limb salvage reconstruction (58%), with the dominant cause of failure being infection. The next most common indication was bone tumour (31%) and the large majority were used in the high risk skeletal locations of the tibia (44%) and the pelvis (27%). Early clinical results are encouraging indicating a significant reduction in the incidence of infection. Three implants have been retrieved. An analysis of a proximal humeral replacement that had been in situ for 6 mths identified that there was 10-20% remaining on the implant surface. This novel process of “stitching-in” silver appears to be a safe and effective surface treatment in helping to control infections of mega-prostheses. This technology has the potential to be transferred to other arthroplasty joints

INTRODUCTION. Post-operative infections following end-stage joint salvage reconstruction, tumor resection and megaprosthetic reconstruction is a major problem because of increasing infection rates in this patient cohort. The success of treatment and longevity is limited because current prosthetic composites do not decrease infection rates in these patients. Silver coating is an innovative development in the prevention of post-operative infection. Presented here is the current knowledge of the use of silver for this patient population including;. The current knowledge of the use of silver coated prostheses for infection control,. Concerns with ion release and toxicity,. Present current published results and USA experience. Discuss current regulatory issues both domestically (USA) and worldwide. METHODS. We report the results of a comprehensive review of the technology of silver coating application to prostheses and the published clinical results of the success of decreasing the incidence of post-operative infection following tumor resection and limb salvage. The current regulatory status of silver use for orthopaedics will also be discussed. DISCUSSION AND CONCLUSION. The potential for the use and success of silver coated megaprostheses following limb salvage and tumor resection is great importance and, based on our review shows significance in the decrease of post-operative infection without adverse issues of silver toxicity (Argyria). This option is an alternative to permanent fusion or the finality of amputation. While the majority of the regulatory world has allowed the routine use of silver coated megaprostheses for infection control, there still exists a few regulatory panels, including the US-FDA, that have yet to approve the routine use of silver coated megaprostheses for infection control following tumor resection and limb salvage

Aim. Silver is known for its excellent antimicrobial activity, including activity against multiresistant strains. The aim of the current study was to analyze the biocompatibility and potential influence on the fracture healing process a silver-coating technology for locking plates compared to silver-free locking plates in a rabbit model. Methods. The implants used in this study were 7-hole titanium locking plates, and plasma electrolytic oxidation (PEO) silver coated equivalents. A total of 24 rabbits were used in this study (12 coated, 12 non-coated). An osteotomy of the midshaft of the humerus was created with an oscillating saw and the humerus stabilized with the 7 hole locking plates with a total of 6 screws. X-rays were taken on day 0, week 2, 4, 6, 8, and 10 for continuous radiographical evaluation of the fracture healing. All animals were euthanized after 10 weeks and further assessment was performed using X-rays, micro-CT, non-destructive four-point bending biomechanical testing and histology. Furthermore, silver concentration was measured in the kidney, liver, spleen and brain. Results. X-rays showed normal undisturbed healing of the osteotomy in all animals without any differences between the two groups over the entire X-ray analysis over 10 weeks (Figure 1). Callus formation was observed up to week 4 to 5 followed by callus remodeling after 6 weeks indicating physiological fracture healing pattern in both the silver and in the silver free group. Micro CT analysis revealed overall tissue (callus and cortical bone) volume as well as tissue density to be comparable between the two groups. Mechanical testing showed comparable stiffness with an average stiffness relative to contralateral bones of 75.7 ± 16.1% in the silver free control group compared to 69.7 ± 18.5% (p-value: 0.46). Histology showed no remarkable difference in the analysis of the healed osteotomy gap or in the surrounding soft tissue area. Silver content was found to be close to baseline values without differences between the two groups. Conclusions. This study shows that the presented antimicrobial silver surface modification for locking plates has a good biocompatibility without any negative influence on the fracture healing processes compared to the silver free control group. This allows for further clinical investigation of this silver technology for locking plates in fracture patients with an elevated infection risk, e.g. in patients with open fractures. For any figures or tables, please contact the authors directly

Foreword. Silver coatings, used in many surgical devices, have demonstrated good antimicrobial activity and low toxicity. Oncological musculoskeletal surgery have an high risk of infection, so in the last decades, silver coated mega-prostheses have been introduced and are becoming increasingly widespread. Material and methods. We performed a retrospective analysis of 158 cases of bone tumors, primary or metastatic, treated between 2002–2014 with wide margins resection and reconstruction with tumoral implants. The average age was 59 years (range 11–78 years), all patients were treated by the same surgeon, with antibiotic prophylaxis according to a standard protocol. In 58.5% of patients were implanted silver-coated prostheses, in the remaining part, standard tumor prosthesis. Patients were re-evaluated annually and were recorded complications, with particular attention to infectious diseases. Results. The mean follow-up was 39.5 months. 23.4% of patients died at a median time of 34.9 months after surgery. 18.4% develop complications that required a new surgery, in 12.6% of cases due to infectious problems. Patients treated with silver-coated implants developed early infection in 2.2% of cases against the 10.7% of the patients treated with standard tumor prosthesis. This different among the two groups was statistically significant, while the percentage of late infections, occurred from 6 months after surgery, was similar between groups. Assuming a reduction of antimicrobial silver activity in the time, it was carried out a microscopic analyses [Fig. 1] of silver-coated prostheses explanted 82 months and 27 months after surgery. It confirmed an important degradation of the coating surface with almost complete absence of silver. Silver blood level, taken in a sample of patients, at different time after surgery, always showed values well below the threshold of toxicity, and no patient has never shown any sign of local or general toxicity secondary to silver [Fig. 2]. Discussion. Our study demonstrates that tumor silver-coated implants have a rate of early infection significantly less than traditional implants, while there were no differences in the rate of late infections, as described also in the literature. This likely is related to wear of the silver coating, which occurs on average around 2 years after implantation. Conclusion. We recommend to use silver–coated prosthesis as primary implants for limb salvage surgery, in primary or metastatic bone tumors, considering the absence of signs of toxicity and the lower rate of early infection

Introduction. Various anti-infective agents can be added to the surface of orthopaedic implants to actively kill bacteria and prevent infection. Silver (Ag) is a commonly used agent in various anti-infective applications. Silver disrupts bacterial membranes and binds to bacterial DNA and to the sulfhydryl groups of metabolic enzymes in the bacterial electron transport chain, thus inactivating bacterial replication and key metabolic processes. Recently we are implanting Silver coated megaprosthesis for the treatment of post-traumatic septic non unions/bone defects and for infected hip or knee prosthesis revision. We treat these complications utilizing a two steps procedure: 1° step: devices removal, resection, debridment and antibiotic spacer implantation; 2° step: spacer removal and megaprosthesis implantation. This technique produce a reactive pseudosynovial membrane, well known in traumatology (Masquelet technique), following the Chamber Induction Technique principles. This chamber creates the perfect environment in which implant the prosthesis with safety. We are nowadays investigating if this membrane could optimize the Silver antimicrobical effects reducing the Silver ions dispersion and reducing toxicity on the human body. Objectives. The aim of this study is to perform a review of the literature about Silver coated implants in Orthopaedics and Trauma and to analyze our cases treated with this implants in order to measure their efficacy and the ion dispersion in urine and blood. Methods. We performed a literature review using the universally validated search engines in the biomedical field: PubMed / Medline, Google Scholar, Scopus, EMBASE. The keywords used were: “Silver”, “Silver coating”, “Silver surface”, “were crossed with “Prosthesis”, “Megaprosthesis”, “Infection”, “Sepsis”, “Revision”. We also analized all our patients treated with Silver coated implants measuring Silver dose in blood and urine before implantation, 1 day after implantation and then after 15 days, 3,6,12,24,36 months. Results. The search led to 468 items, of these were considered only article in English with full text available. We found 1 in vitro study, 1 animal study and 2 human studies. The animal study showed a reduction in periprosthetic infection from 47% to 7%, 1 human study in Oncology application of megaprosthesis showed a reduction of septic complications from 17,6% to 5,9%. Te other human study demonstrated that Silver surface implants don't have toxicity cause the blood level of silver Ions were only 56,4 parts per billion. The analysis of our casuistry is giving good results with low level of Silver in the blood and urine, lower concentrations are observed in patients treated with the 2 steps-CIT technique. Conclusions. The use of silver-coated prosthesis can reduce the infection rate in the medium-long term with no toxicity for the patients. Further studies with longer term follow-up periods and larger numbers of patients are warranted in order to confirm these encouraging results most of all in the patients treated with the 2 steps procedure in order to better understand the role of the membrane and of the Chamber Induction Technique in Silver ions dispersions

Introduction. Titanium (Ti) alloys are used as porous bone ingrowth materials on non-cemented knee arthroplasty tibial tray implants. Nano-surface mechanism that increase the osseointegration rate between Ti alloys, and surrounding tissue has been recognized to improve the interface to ultimately allow patients to weight bear on non-cemented arthroplasty implants sooner. Bioactive TiO. 2. nanotube arrays has been shown to accelerate osseointegration. Ideally, these surfaces would both increase the adhesion of bone to the implant and help to reduction of infection to substitute for antibiotic bone cement. This study examines a combination treatment of both TiO. 2. nanotubes combined with silver nano-deposition, that simultaneously enhances osseointegration while improving infection resistance, by testing ex vivo implantation stability in an equine cadaver bone followed by in vitro and in vivo analysis to understand the biocompatibility and early stage osseointegration. Methods. 100nm diameter and 300nm length TiO. 2. nanotubes were formed on a CP titanium surface using anodization method at 20V for 45mins using 1% HF electrolyte. Silver deposition on TiO. 2. nanotubes were performed using 0.1M AgNO. 3. solution at 3V for 45s. Figure 1 shows SEM images showing (a) TiO. 2. nanotubes of 300nm length and (b) nanotubes with silver coating). Ti anodized samples with and without silver nanotubes implanted into an equine cadaver bone in an ex vivo manner to study the stability of nanotubes and the adherence of silver deposition. Silver release study was performed for a period of 14 days in a similar ex vivo manner. Dimensions for implantation samples: 2.5 mm diam. × 15 mm. For cell culture, circular disc samples 12.5mm in diameter and 3 mm in thickness were used to study the bone cell-material interactions using human fetal osteoblast (hFOB) cells. To evaluate the cell proliferation, MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay was used. The in vitro cell-materials interaction study was performed for a period of 4 and 7 days. In vivo study was performed using rat distal femur model for a period of 12 weeks with dense Ti samples as control (Sample dimensions: 3mm diam. × 5mm). At the end of 12 weeks, the samples were analyzed for early stage osseointegration using histological analysis and SEM imaging. Results. No significant changes in the morphology of nanotubes was observed due to the implantation process which signifies the damage resistance these nanotubes can endure during implantation and explantation. Figure 2 shows SEM images of (a) & (b) nanotubes without silver coating before and after implantation and (c) & (d) nanotubes with silver coating before and after implantation respectively. Silver nanocoatings can be observed after implantation which shows the adherence of the antimicrobial nano-coating on the surface of nanotubes. Cumulative release profiles of silver ions after 14 days showed the total release was in the effective range for antimicrobial characteristics and was well below the toxic limit specified for human cells (10 ppm) Figure 3(a) shows cumulative release profile of silver after 14 days. MTT assay and SEM images show good cell proliferation, antimicrobial effect, and increase in cell density after 7 days for samples with nanotubes and silver with no cytotoxic effects and good cell attachment on the samples as shown in Figure 3(b) MTT assay results showing cell densities after 4 and 7 days and Figure 3(c) SEM images showing cell attachment after 4 and 7 days on samples. Histological analysis and SEM images showed osteoid formation around the implant with improved bonding towards the implant and bone showing signs of early stage osseointegration. Figure 4 shows histological and SEM images showing bonding between bone and implant surface for respective samples after 12 weeks. Conclusions. Mechanically stableTiO. 2. nanotubes with strongly adhered antimicrobial silver coating were grown on the surface of titanium which were biocompatible and non-toxic. In vitro and in vivo tests indicate improved cell-materials interaction with signs of early stage osseointegration. This nano-surface treatment shows promise towards simultaneously improving early stage osseointegration and providing an infection barrier on bone ingrowth materials

Aim. In patients with bone sarcoma, placing mega prostheses in the proximal tibia is associated with high rates of infection. In studies with small numbers of patients and short follow-up periods, silver-coated mega prostheses have been reported to lead to reduced infection rates. To the best of our knowledge, this study is the largest one that has compared the infection rates with titanium versus silver-coated mega prostheses in patients treated for sarcomas in the proximal tibia. Method. The infection rate in 98 patients with sarcoma or giant cell tumour in the proximal tibia who underwent placement of a titanium (n = 42) or silver-coated (n = 56) mega prosthesis. *. was assessed, along with the treatments administered for any infection. Results. As the primary end point of the study, the rates of infection were 16.7% in the titanium group and 8.9% in the silver group, resulting in 5-year prosthesis survival rates of 90% in the silver group and 84% in the titanium group. Overall, seven of 56 patients in the silver group (12.5%) developed periprosthetic infection. Two patients became infected after revision surgery due to mechanical failure of the prosthesis. In the titanium group, one patient developed a periprosthetic infection after revision surgery (which was carried out in 50% of patients) due to a mechanical prosthetic failure, leading to an overall infection rate of 19.0% (eight of 42). Overall, nine of 12 (75%) periprosthetic infections in the two groups occurred within the first 2 years postoperatively, if later revision surgery due to mechanical failure was not necessary. Whereas three of the eight patients in the titanium group (37.5%) ultimately had to undergo amputation due to infected proximal tibia replacement, these mutilating surgical procedures were necessary in the silver group in only one patient (14.3%). In the titanium group, two-stage revision surgery with a temporary antibiotic-impregnated cement spacer was ultimately successful in four of eight patients (50.0%), but this procedure was necessary in only one patient in the silver group (14.3%). Conclusions. The use of silver-coated prostheses reduced the infection rate in a relatively large and homogeneous group of patients. In addition, less aggressive treatment of infection was possible in the group with silver-coated prostheses

Introduction. Revision of total hip replacements (THRS) is predominantly due to aseptic loosening, pain and infection [1]. The current method used to address the risk of infection is to administer antibiotics and to include antibacterial agents into bone cement (if used) and on implant coatings [2–4]. Currently, silver (Ag) coatings have only been applied to titanium hip stems [3]. Cobalt chromium alloy (CoCr) is a widely used orthopaedic alloy which is commonly used as a bearing surface; revisions of joints using this material often describe adverse reactions to the particulate wear debris [1]. This study considers an Ag containing CrN based coating on a CoCr substrate with the aim to reduce cobalt (Co) release and promote antibacterial silver release. Methods. Silver Chromium Nitride (CrNAg) coatings were developed and applied onto the bearing surfaces of 48 mm diameter metal-on-metal THRs. Three coatings were evaluated: high Ag at the surface (CrNAg+), low Ag at surface (CrNAg-) and uniform Ag (CrNAg=). All bearings were tested under ISO 14242-3 conditions for 0.17 million cycles (mc) representing approximately 2 months use in vivo. Wear was determined gravimetrically; Ag and Co levels in the lubricant were measured using graphite furnace atomic absorption spectroscopy. Testing of the CrNAg= bearings were continued to 2mc under standard conditions; CrNAg- bearings to 5mc incorporating lateralisation, which created separation at swing phase and rim contact at heel strike. Wear volume and Ag/Co release were monitored at 0.33, 0.67, 1mc and every mc thereafter. Results. All bearings produced low levels of wear and released silver into the lubricating fluid. An increase in silver concentration at the surface of the bearings was found to increase both the silver released and wear, Figure 1. Negligible cobalt was released. Testing of the CrNAg= coating to 2mc showed the wear rate to decrease after 0.17mc, Figure 2. Ag release continued up to 2mc but at a decreased rate. The CrNAg- coating tested under lateralisation conditions to 5mc showed no coating failure and negligible cobalt release. Wear and silver release showed similar patterns and reached a steady state after 1mc, Figure 3. Discussion. The AgCrN coatings on bearing surfaces of a hip joint are capable of releasing Ag at concentrations within the ‘No Observable Adverse Effect Limit’ [5]. These coatings also prevented Co release while maintaining a low wear rate. All coatings remained intact and did not delaminate, even under adverse conditions. These coatings have been tested in a metal-on-metal hip bearing surface, the most controversial and challenging condition for a coating, wearing against itself. CoCr is used as a bearing surface against polyethylene in hips and knees, in stems and tapers, as tibial trays in knee replacement and as shells for acetabular cups. This coating may be applied to a wide range of applications, removing some of the challenges over the use of CoCr while reducing infections

Our previous study has revealed that silver nanoparticles (AgNPs) have potential to promote wound healing by accelerated re-epithelization and enhanced differentiation of fibroblasts. However, the effect of AgNPs on the functionality of repaired skin is unknown. The aim of this study was to explore the tensile properties of healed skin after treatment with AgNPs. Immunohistochemical staining, quantitative assay and scanning electron microscopy (SEM) were used to detect and compare collagen deposition, and the morphology and distribution of collagen fibers. Our results showed that AgNPs improved tensile properties and led to better fibril alignments in repaired skin, with a close resemblance to normal skin. Based on our findings, we concluded that AgNPs were predominantly responsible for regulating deposition of collagen and their use resulted in excellent alignment in the wound healing process. The exact signaling pathway by which AgNPs affect collagen regeneration is yet to be investigated

Bacterial infection related to prosthetic replacement is one of the serious types of complications. Recently, there has been a greater interest in antibacterial biomaterials. In order to reduce the incidence of replacement-associated infections, we developed a novel coating technology of Hydroxyapatite (HA) containing silver (Ag). We reported the Ag-HA coating showed high antibacterial activity against E. coli, S. aureus and methicillin-resistant S. aureus (MRSA) under static condition. However, human bodies have a circulating body fluid, which is not a static condition. And the growth and the maturation of biofilm, which is said that a common course of persistent infections at a surgical site, are enhanced by the flow of broth in culture environment. Therefore, we evaluated whether the Ag-HA coating inhibits the biofilm formation on its surface or not by a biofilm-forming test under flow condition in this study. Ag-HA or HA powder was sprayed onto the commercial pure titanium disks using a flame spraying system. The HA coating disks were used as negative control. The biofilm-forming methicillin sensitive S. aureus (BF-MSSA; Seattle 1945) strain and the BF-MRSA (UOEH6) strain were used. The pre-culture bacterial suspension (about 10. 5. colony forming units; CFU) was inoculated onto the Ag-HA and HA coating disks. After cultivation at 37 °C for 1 h, the disks were rinsed twice with 500 μL sterile PBS (-) to eliminate the non-adherent bacteria. The number of the adherent bacteria on these disks was counted using culture method. After rinsing, the disks were transferred into petri-dish containing Trypto–Soy Broth (TSB) + 0.25% glucose with a stirring bar on the magnetic stirrer and they were cultured at 37°C for 7 days. In the meantime, the stirring bar was spun at 60 rounds per minute. Then, the disks were immersed in a fluorescent reagent to stain the biofilm. Finally, the biofilm on each disk was observed by a fluorescence microscope and the biofilm-covered rate on the surfaces of them was calculated using the NIH image software. The number of the bacteria on these disks was not so different between Ag-HA and HA coating after rinsing. After biofilm-forming test, the coverage of the biofilm of BF-MSSA was 2.1% and 81.0% on the Ag-HA and HA coatings, respectively. Similarly, in the case of BF-MRSA, it was 7.7% and 72.0% on the Ag-HA and HA coatings, respectively. Though bacteria slightly adhered, biofilm was hardly observed on the Ag-HA coating. The biofilm on the HA coating was extensive and mature. The inhibition effect of biofilm formation on the Ag-HA coating might be ascribed to the antibacterial effect by Ag ions released from the coating. Because Ag ions have a broad spectrum of antibacterial activity against pathogens, including biofilm forming bacteria, they inhibited the biofilm formation on the Ag-HA coating by killing adherent bacteria. Even in a flow condition, it was suggested that the AgHA shows the antibacterial activity, though the conditions in this work are different from those in living body

Problems. Biofilm infections are increasingly associated with orthopedic implants. Bacteria form biofilms on the surfaces of orthopedic devices. The biofilm is considered to be a common cause of persistent infections at a surgical site. The growth and the maturation of biofilm are enhanced by the flow of broth in culture environment. In order to reduce the incidence of implant-associated infections, we developed a novel coating technology of hydroxyapatite (HA) containing silver (Ag). We previously reported that the Ag-HA coating inhibits biofilm formation under flow condition of Trypto Soy Broth + 0.25% glucose for 7 days. In this study, we evaluated whether the Ag-HA coating continuously inhibits the biofilm formation on its surface under flow condition of fetal bovine serum, which contains many in vivo substrates such as proteins. Materials and Method. The commercial pure titanium disks were used as substrates. Ag-HA or HA powder was sprayed onto the substrates using a flame spraying system. The HA coating disks were used as negative control. The biofilm-forming methicillin resistant Staphylococcus aureus (BF-MRSA; UOEH6) strain was used. The bacterial suspension (about 10. 5. colony forming units) was inoculated into 24-well sterile polystyrene tissue culture plates. The Ag-HA and HA coating disks were aseptically placed in the wells. After cultivation at 37°C for 1 hour, the disks were rinsed twice with 500 μL sterile PBS (−) to eliminate the non-adherent bacteria. After rinsing, the disks were transferred into petri-dish containing heat-inactivated FBS with a stirring bar on the magnetic stirrer and they were cultured at 37 °C for 24 hours, 7 and 14 days. In the meantime, the stirring bar was spun at 60 rounds per minute. Then, the disks were immersed in a fluorescent reagent to stain the biofilm. Finally, the biofilm on each disk was observed by a fluorescence microscope and the biofilm-covered rate (BCR) on the surfaces of them was calculated using the NIH image software. Results. Biofilm was hardly observed on the Ag-HA coating. However, the biofilm on the HA coating was extensive and mature (Fig. 1). At 24h after cultivation, BCRs of BF-MRSA were 2.1% and 19.8% on the Ag-HA and HA coatings, respectively. Similarly, they were 6.3% and 12.4% on the Ag-HA and HA coatings at 7 days. At 14 days they were 20.6% and 39.4% on the Ag-HA and HA coatings, respectively. These results demonstrate that BCRs on the Ag-HA coating were significantly lower than those on the HA coating (Fig. 2). Discussion. The Ag-HA coating continuously showed the inhibiting ability for biofilm formation under flow condition for 14 days. Ag ions inhibited the biofilm formation on the Ag-HA coating by killing adherent bacteria in the vicinity of the surface, although the release rate of Ag ions was high until 24h after immersion and decreased thereafter. The Ag-HA coating would be expected to contribute to reduction of implant-related biofilm infection

Aim. A novel anti-infective biopolymer implant coating was developed to prevent bacterial biofilm formation and allow on-demand burst release of anti-infective silver (Ag) into the surrounding of the implant at any time after surgery via focused high-energy extracorporeal shock waves (fhESW). Method. A semi-crystalline Poly-L-lactic acid (PLLA) was loaded with homogeneously dissolved silver (Ag) applied onto Ti6Al4V discs. A fibroblast WST-1 assay was performed to ensure adequate biocompatibility of the Ag concentration at 6%. The prevention of early biofilm formation was investigated in a biofilm model with Staphylococcus epidermidis RP62A after incubation for 24 hours via quantitative bacteriology. In addition, the effect of released Ag after fhESW (Storz DUOLITH SD1: 4000 impulses, 1,24 mJ/mm. 2. , 3Hz, 162J) was assessed via optical density of bacterial cultures (Escherichia coli TG1, Staphylococcus epidermidis RP62A, Staphylococcus aureus 6850) and compared to an established electroplated silver coating. The amount of released Ag after the application of different intensities of fhESW was measured and compared to a control group without fhESW via graphite furnace atomic absorption spectrometry (GF-AAS), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Results. The coating with 6% Ag reduced Staphylococcus epidermidis biofilm formation by 99.7% (mean±SD: 2.1×10^5 ± 3,9×10^5 CFU/µL) compared to uncoated controls (6.8×10^7 ± 4.9×10^7 CFU/µL); (p=0.0001). After applying fhESW the commercially available electroplated silver coating did not prevent the growth of all tested bacterial strains. Bacterial growth is delayed with 4% Ag and completely inhibited with 6% Ag in the novel coating, except for a small increase of S. aureus after 17 hours. SEM and EDS confirmed a local disruption of the coating after fhESW. Conclusions. This novel anti-infective implant coating has the potential to prevent bacterial biofilm formation. The on-demand burst release of silver via fhESW could be an adjunctive in the treatment of implant related infection and is of particular interest in the concept of single stage revision surgery

Complex acetabular reconstruction for oncology and bone loss are challenging for surgeons due to their often hostile biological and mechanical environments. Titrating concentrations of silver ions on implants and alternative modes of delivery allow surgeons to exploit anti-infective properties without compromising bone on growth and thus providing a long-term stable fixation. We present a case series of 12 custom acetabular tri-flange and custom hemipelvis reconstructions (Ossis, Christchurch, New Zealand), with an ultrathin plasma coating of silver particles embedded between layers of siloxane (BioGate HyProtect™, Nuremberg, Germany). At the time of reporting no implant has been revised and no patient has required a hospital admission or debridement for a deep surgical site infection. Routine follow up x-rays were reviewed and found 2 cases with loosening, both at their respective anterior fixation. Radiographs of both cases show remodelling at the ilium indicative of stable fixation posteriorly. Both patients remain asymptomatic. 3 patients were readmitted for dislocations, 1 of whom had 5 dislocations within 3 weeks post-operatively and was immobilised in an abduction brace to address a lack of muscle tone and has not had a revision of their components. Utilising navigation with meticulous implant design and construction; augmented with an ultrathin plasma coating of silver particles embedded between layers of siloxane with controlled and long-term generation of silver ion diffusion has led to outstanding outcomes in this series of 12 custom acetabular and hemipelvis reconstructions. No patients were revised for infection and no patients show signs of failure of bone on growth and incorporation. Hip instability remains a problem in these challenging mechanical environments and we continue to reassess our approach to this multifaceted problem

The reconstruction of peri-acetabular defects after severe bone loss or pelvic resection for tumor is among the most challenging surgical intervention. The Lumic® prosthesis (Implantcast, Buxtehude, Germany) was first introduced in 2008 in an effort to reduce the mechanical complications encountered with the classic peri-acetabular reconstruction techniques and to improve functional outcomes. Few have evaluated the results associated with the use of this recent implant. A retrospective study from five Orthopedic Oncology Canadian centers was conducted. Every patient in whom a Lumic® endoprosthesis was used for reconstruction after peri-acetabular resection or severe bone loss with a minimal follow-up of three months was included. The charts were reviewed and data concerning patients’ demographics, peri-operative characteristics and post-operative complications was collected. Surgical and functional outcomes were also assessed. Sixteen patients, 11 males and five females, were included and were followed for 28 months [3 – 60]. Mean age was 55 [17–86], and mean BMI reached 28 [19.6 – 44]. Twelve patients (75%) had a Lumic® after a resection of a primary sarcoma, two following pelvic metastasis, one for a benign tumor and one after a comminuted acetabular fracture with bone loss. Twelve patients (75%) had their surgery performed in one stage whereas four had a planned two-stage procedure. Mean surgical time was 555 minutes [173-1230] and blood loss averaged 2100 mL [500-5000]. MSTS score mean was 60.3 preoperatively [37.1 – 97] and 54.3 postoperatively [17.1-88.6]. Five patients (31.3%) had a cemented Lumic® stem. All patients got the dual mobility bearing, and 10 patients (62.5%) had the largest acetabular cup implanted (60 mm). In seven of these 10 patients the silver coated implant was used to minimize risk of infection. Five patients (31.3%) underwent capsular reconstruction using a synthetic fabric aiming to reduce the dislocation risk. Five patients had per-operative complications (31.3%), four were minor and one was serious (comminuted iliac bone fracture requiring internal fixation). Four patients dislocated within a month post-operatively and one additional patient sustained a dislocation one year post-operatively. Eight patients (50%) had a post-operative surgical site infection. All four patients who had a two-stage surgery had an infection. Ten patients (62.5%) needed a reoperation (two for fabric insertion, five for wash-outs, and three for implant exchange/removal). One patient (6.3%) had a septic loosening three years after surgery. At the time of data collection, 13 patients (81.3%) were alive with nine free of disease. Silver coating was not found to reduce infection risk (p=0.2) and capsuloplasty did not prevent dislocation (p=1). These results are comparable to the sparse data published. Lumic® endoprosthesis is therefore shown to provide good functional outcomes and low rates of loosening on short to medium term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and of the use of silver coated implants. Larger series and longer follow-ups are needed

The reconstruction of peri-acetabular defects after severe bone loss or pelvic resection for tumor is among the most challenging surgical intervention. The Lumic® prosthesis (Implantcast, Buxtehude, Germany) was first introduced in 2008 in an effort to reduce the mechanical complications encountered with the classic peri-acetabular reconstruction techniques and to improve functional outcomes. Few have evaluated the results associated with the use of this recent implant. A retrospective study from five Orthopedic Oncology Canadian centers was conducted. Every patient in whom a Lumic® endoprosthesis was used for reconstruction after peri-acetabular resection or severe bone loss with a minimal follow-up of three months was included. The charts were reviewed and data concerning patients’ demographics, peri-operative characteristics and post-operative complications was collected. Surgical and functional outcomes were also assessed. Sixteen patients, 11 males and five females, were included and were followed for 28 months [3 – 60]. Mean age was 55 [17-86], and mean BMI reached 28 [19.6 – 44]. Twelve patients (75%) had a Lumic® after a resection of a primary sarcoma, two following pelvic metastasis, one for a benign tumor and one after a comminuted acetabular fracture with bone loss. Twelve patients (75%) had their surgery performed in one stage whereas four had a planned two-stage procedure. Mean surgical time was 555 minutes [173-1230] and blood loss averaged 2100 mL [500-5000]. MSTS score mean was 60.3 preoperatively [37.1 – 97] and 54.3 postoperatively [17.1-88.6]. Five patients (31.3%) had a cemented Lumic® stem. All patients got the dual mobility bearing, and 10 patients (62.5%) had the largest acetabular cup implanted (60 mm). In seven of these 10 patients the silver coated implant was used to minimize risk of infection. Five patients (31.3%) underwent capsular reconstruction using a synthetic fabric aiming to reduce the dislocation risk. Five patients had per-operative complications (31.3%), four were minor and one was serious (comminuted iliac bone fracture requiring internal fixation). Four patients dislocated within a month post-operatively and one additional patient sustained a dislocation one year post-operatively. Eight patients (50%) had a post-operative surgical site infection. All four patients who had a two-stage surgery had an infection. Ten patients (62.5%) needed a reoperation (two for fabric insertion, five for wash-outs, and three for implant exchange/removal). One patient (6.3%) had a septic loosening three years after surgery. At the time of data collection, 13 patients (81.3%) were alive with nine free of disease. Silver coating was not found to reduce infection risk (p=0.2) and capsuloplasty did not prevent dislocation (p=1). These results are comparable to the sparse data published. Lumic® endoprosthesis is therefore shown to provide good functional outcomes and low rates of loosening on short to medium term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and of the use of silver coated implants. Larger series and longer follow-ups are needed

This study was performed to investigate the concentration of silver ions release up to a time of 9 weeks as well as the antimicrobial activity of silver sulfate and Nano-silver mixed bone cement on Candida albicans, in expectation of a new way of therapy in manner of a time limited application – a silverions releasing bone cement spacer. Two different kinds of silver products were used and mixed with polymethylmetacrylate (PMMA, De Puy) bone cement:. Nano-silver with a particle size of 5–50 nm and active surface of 4 m2/ g. (Nanonet Styria, Austria). Silver sulfate in a finely powdered form (Fisher, GB). Concentrations of 0.1%, 0.5%, 1% and 5% of the Nano-silver and the silver-salt by weight were mixed with the dry powder portion of the cement. To test the silver-ions release from the silver-containing bone cement two models of elution, a static model and a dynamic model were created. To test the antifungal effectiveness of the various concentrations of Ag-PMMA the bone cement samples were tested by agar diffusion assay. With respect to minimal inhibition concentration (MIC) the sample containing 0.5 % silver sulfate showed required concentration at the dynamic elution model but none of the nano-silver samples did. In static elution model we measured the maximum concentration of 466.5 µg/l at the 0.5 % silver sulfate sample which is much below the toxic concentration. Agar diffusion assay showed no zone of inhibition from Nano-silver samples. In contrast, silver sulfate containing samples showed a zone of inhibition exactly growing, depending on the samples silver sulfate concentration. According to results, silver sulfate addition to PMMA might be another approach in treatment of candida associated periprosthetic joint infection

Aim. Aim of this study was to establish the first clinical results after implantation of ultrathin silver-polysiloxane-coated. 1. plates in the treatment of infected non-union of the femoral shaft. Method. As part of the REFECT study, a prospective, non-interventional analysis was conducted encompassing all patients who received internal stabilization with a silver-coated. 1. plate from 01/2023 to 09/2024 as part of the treatment for infected non-union of the femur. Standardized clinical follow-ups including PROMs (WOMAC-Index, LEF-S, EQ-5D, VAS) and X-rays were performed 3, 6, 12 (and 24) months postoperatively. For comparison, a retrospective analysis of 76 patients with infected femoral non-union, who had received a stabilization with an uncoated plate in the past 10 years, was performed. Results. The mean follow-up of the 8 included patients (mean bone defect: 3.6 cm) was 9 months (as of 04/24). Multiresistant bacteria were found in the intraoperative samples of 5 patients. The concentration of silver ions in blood serum reached a maximum of 0.014 mg/l in the laboratory controls. All patients showed a positive healing process with no sign of re-infection and no adverse procedure-associated events. Full weight bearing was achieved after an average of 4 months (n=6) with improved WOMAC-, LEF-S-, EQ-5D and VAS-score at 1-year FU. In the reference group (uncoated, mean FU: 3.5 years), there was a re-infection rate of 25 %, mostly in the first 2 years. Difficult-to-treat bacteria were detected in 22%, multiresistant Staph. epidermidis in 28% of cases. Conclusions. -. The silver-coated. 1. implants showed good biocompatibility with no evidence of procedure-associated complications. -. The use of silver-coated. 1. implants could reduce the risk of re-infection. -. Further clinical data with longer follow-up are needed to assess the long-term value of the procedure