Aim. Diagnostics of orthopedic implant infection remains challenging and often shows false negative or inadequate results. Several methods have been described to improve diagnostic methods but most of them are expensive (PCR) or not accessible for all hospitals (sonication). Aim of this study was to evaluate the results of incubation of orthopedic explants compared to biopsies and punction fluid using conventional microbiological methods. Method. In this prospective study, we included patients who received septic or aseptic orthopedic implant removal in a single University hospital between July and December 2018. A part of the explant as well as minimum 2 tissue biopsies or additional punction fluid were put in a bouillon and incubated for 11 days. Patient´s records with co-morbidities, use of antibiotics and demographic data were evaluated. The results were analyzed. The study was approved by the ethical committee. Results. 94 patients were included in this study (43 females, 51 males, mean age 54 years). We detected statistically significant more pathogens in the bouillon with explants compared to biopsies (p=0,0059). We found the same results with pedicle screws (n=11, p=0,039) and endoprosthesis (n=56, p=0,019). Patients after osteosynthesis (p=27) showed same results but statistically not significant (p=0,050). Use of antibiotics did not have influence on the diagnostic result as well as co-morbidities. In 38 patients (40,4%), additional bacteria could be detected in explant´s bouillon. Most common pathogens were Staph. aureus, E. faecalis, Staph. epidermidis and Micrococcus luteus, mixed infections could be found in 9%. Conclusions. In this study we could show that incubation of orthopedic implants has advantages in diagnostics of pathogens in infected endoprosthesis, osteosynthesis and spondylodesis. This method is simple compared to PCR or sonication and as cheap as incubation of tissue samples but in 40% of the cases, additional pathogens can be detected. We recommend to incubate removed screws, hip endoprosthetic heads or inlays in bouillon to optimize diagnostics and to detect all pathogens

Purpose: Peri-implant osteolysis after total joint arhtro-plasty (TJA) is a major cause of implant loosening. Cellular responses to wear particles have been reported to play a role in asceptic loosening due to their cytotoxic nature to cellular components. Purpose of this study is to evaluate the effect of orthopedic implant wear particles on immature osteoblasts in an in-vitro setting in order to further understand the mechanisms involved in asceptic loosening of implants. Methods: Stromal cells from femurs of 30 day-old Swiss Webster Mice were isolated, cultured in-vitro, and incubated with Titanium and Ceramic (smooth and angular) particles in the micrometer size range. After 9 days of incubation the cells were assessed for Alkaline phosphatase (ALP) activity or stained for cellular changes consistent with apoptosis. Results: Here we report both a dose-dependent decrease (P< 0.05) in ALP activity and a significant increase in programmed cell death when murine stromal cells were cultured with orthopedic implant wear particles of differing compositions. Ceramic wear particles were consistently less toxic at lower concentrations (1 x 107 to 2 x 107 particles/ml) than were wear particles composed of titanium. However, at high concentrations (4 x 107 particles/ml) all particles regardless of composition were equally toxic. These findings suggest that ceramic particles may be less cytotoxic to bone marrow stromal cells/osteoblasts than are titanium particles. Conclusions: Previous studies have suggested that inflammatory responses to orthopedic wear particles are responsible for the asceptic loosening of orthopedic implants. In the current study however, we found that wear particles may also induce cellular apoptosis of primary bone forming cells. This suggests that the asceptic loosening of orthopedic implants may be independent of inflammatory processes, and that implant material selection should be directed, in part, by its inability to cause programmed cell death

Introduction: In recent years the implementation of sonication in the diagnosis of orthopaedic implant infections has improved the detection of subclinical infections. With the use of sonication of removed orthopaedic material we can detect the presence of biofilm. The method has already shown encouraging results, especially in cases of preoperative antibiotic therapy. Aim: The aim of the study was to detect infections of orthopaedic material using both sonication and standard diagnostic methods, and to compare the obtained results of both methods. For the purpose of the study we sonicated all explanted material at revision surgery and cultured the obtained samples. During revision surgery soft tissue biopsies were collected and analyzed using standard microbiologic methods. The results were compared, analyzed and additional therapy was applied, if an infection of the material was proven. During the period from September 2009 to the end of March 2014 we studied 249 cases (198 patients) of revision surgery (166 cases of revision hip arthroplasty, 53 cases of revision knee arthroplasty, 13 cases of revision foot surgery, 17 cases of revision spine surgery). Of studied cases infection was proven in 20 (8,0%) cases by soft tissue biopsies only, 90 cases (36,1%) were diagnosed both by soft tissue biopsies and sonication, 45 cases (18,1%) were diagnosed only by sonication of explanted prosthetic material and in 94 cases (37,8%) all results were negative. The statistical analysis has shown statistically significant (p<0,05) improvement of infection detection using sonication. According to our experience the implementation of sonication has shown an improvement in the diagnosis of orthopaedic implant infections. Despite certain limitations, sonication should be considered in doubtful cases of revision surgery. The use of sonication should be emphasized in cases of preoperative antibiotic treatment

Aseptic loosening of orthopaedic implants has a major financial impact on the Health Service. The process is thought to be caused by wear particles that are phagocytosed by macrophages and hence stimulate bone resorption via a cytokine response. Previous work suggests that factors inhibiting or enhancing bone resorption act through regulation of the OPG and RANK-L mechanism. The objective of this study was to identify the role of RANK-L and OPG within the cytokine response leading to orthopaedic implant loosening. Ten samples of cellular membrane obtained during revision arthroplasty surgery were analysed with basic histological staining, immunohistology and polymerase chain reaction (PCR). In vitro studies were also carried out using explanted cancellous bone, to which PMMA particles were added and bone resorbing osteoclastic cells were identified by their Tartrate-Resistant Acid Phosphatase (TRAP) activity. PCR identified the presence of OPG in all of the periprosthetic samples, with RANK-L shown in 40% of the specimens. Immunoreactivity was shown for CD3, CD68 and RANK-L. In vitro studies confirm that there is an initial burst of inflammatory cytokine activity that then subsequently plateaus. A balance of RANK-L and OPG regulates bone resorption at the bone/implant interface of implants by stimulating a significant initial inflammatory response which leads to loosening

Background of Study. Identification of the exact make and model of an orthopaedic implant prior to a revision surgery can be challenging depending upon the surgeon's experience and available knowledge base about the available implants. The current identification procedure is manual and time consuming as the surgeon may have to do a comprehensive search within an online database of radiographs of an implant to make a visual match. There is further time lapse in contacting that particular implant manufacturer to confirm the make and model of the implant and then order the whole inventory for the revision surgery. This leads to delay in treatment thus requiring extra hospital bed occupancy. Materials and Methods. We have analysed image recognition techniques currently in use for image recognition to understand the underlying technologies based on an interface commonly known as Application Programming interface (API). These API's specifies how the software components of the proposed application interact with each other. The objective of this study is to leverage one or a combination of API's to design a fully functional application in the initial phase and that can help recognize the implant accurately from a large database of radiographs and then develop a specialized and advanced API/Technology in the implant identification application. Results. Our study takes into account the existent technologies such as Facebook, Pictoria, Imagga, Google images. We found that there is an API currently available that can be directly applied to build an implant recognition system. However, commonly known Facebook's image tagging algorithms to store unique information with each image is the starting point to help build an intelligent system that in combination with image processing and development of a custom implant recognition API. Conclusion. There is an urgent need to have a robust and accurate system for identification of orthopaedic implants. Revision surgeries may need to be carried out by hospitals without access to index surgery operating notes. Patients may approach the most convenient not necessarily the same surgeon for a revision surgery. The dependency upon surgeon's experience, hospitals facilities and archiving of records can be avoided with the use of a single application that allows multiple manufacturers to contribute to a database of catalogue of their products

Background and aim. Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low it is crucial to achieve adequate antibiotic concentrations proximate to the implant for a sufficient amount of time to protect the implant surface and ensure tissue integration. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant inserted in cancellous bone. Method. Six female pigs received an intravenous bolus infusion of 4 g/0.5 g piperacillin/tazobactam over 30 min every 6 h. Steady state was assumed achieved in the third dosing interval (12–18 h). Microdialysis catheters were placed in a cannulated screw in the proximal tibial cancellous bone, in cancellous bone next to the screw, and in cancellous bone on the contralateral tibia. Dialysates were collected from time 12 to 18 h and plasma samples were collected as reference. Results. Time above the minimal inhibitory concentration (fT>MIC) was evaluated for MIC of 8 (low target) and 16 μg/mL (high target). For the low piperacillin target (8 μg/mL), comparable mean fT>MIC across all the investigated compartments (mean range: 54–74%) was found. For the high target (16 μg/mL), fT>MIC was shorter inside the cannulated screw (mean: 16%) than in the cancellous bone next to the screw and plasma (mean range: 49–54%), and similar between the two cancellous bone compartments. Conclusions. To reach more aggressive piperacillin fT>MIC targets in relation to the implant, alternative dosing regimens such as continuous infusion may be considered

Objectives. Infection of implants is a major problem in elective and trauma surgery. Heating is an effective way to reduce the bacterial load in food preparation, and studies on hyperthermia treatment for cancer have shown that it is possible to heat metal objects with pulsed electromagnetic fields selectively (PEMF), also known as induction heating. We therefore set out to answer the following research question: is non-contact induction heating of metallic implants effective in reducing bacterial load in vitro?. Methods. Titanium alloy cylinders (Ti6Al4V) were exposed to PEMF from an induction heater with maximum 2000 watts at 27 kHz after being contaminated with five different types of micro-organisms: Staphylococcus epidermidis; Staphylococcus aureus; Pseudomonas aeruginosa; spore-forming Bacillus cereus; and yeast Candida albicans. The cylinders were exposed to incremental target temperatures (35°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C) for up to 3.5 minutes. Results. There was an average linear heating rate of 0.39°C per second up to the target temperature, and thereafter the target temperature was maintained until the end of the experiment. At 60°C and higher (duration 3.5 minutes), there was a 6-log reduction or higher for every micro-organism tested. At 60°C, we found that the shortest duration of effective induction heating was 1.5 minutes. This resulted in a 5-log reduction or higher for every micro-organism tested. Conclusion. Non-contact induction heating of a titanium disk is effective in reducing bacterial load in vitro. These promising results can be further explored as a new treatment modality for infections of metal orthopaedic implants. Cite this article: B. G. Pijls, I. M. J. G. Sanders, E. J. Kuijper, R. G. H. H. Nelissen. Non-contact electromagnetic induction heating for eradicating bacteria and yeasts on biomaterials and possible relevance to orthopaedic implant infections: In vitro findings. Bone Joint Res 2017;6:323–330. DOI: 10.1302/2046-3758.65.BJR-2016-0308.R1

Introduction. Metal alloys have been commonly used for surgical applications due to their suitable mechanical characteristics and relatively good biocompatibility. However, direct cellular corrosion of orthopaedic implants remains a controversial topic and is still not fully understood. This study aims to examine a possible aspect of this corrosion mechanism by determining if macrophages can attach and directly affect the surfaces of 316L stainless steel, Ti6Al4V, and CoCrMo by releasing components of the alloy oxide layer. Methods. IC-21 ATCC peritoneal macrophages were cultured with growth medium of RPMI 1640 with 10%FBS, L-glutamine, and gentamicin. Interferon Gamma (IFNy) and Lipopolysaccharide (LPS) were used to induce activation of macrophages. Stainless Steel, CoCr, and Titanium disks cut, polished, and placed into a 96 well plate. Stainless steel testing included 6 groups: standard medium, 20,000 cells, 40,000 cells, 20,000 activated cells, 40,000 activated cells. CoCr and Ti testing included the following: medium, 40,000 cells, 20,000 activated cells, cells, no disk + 20,000 cells, no disk + 40,000 cells. After cells were attached to the surface, culture media was replaced and collected every 24 hours for stainless steel and every 12 hours for Ti and CoCr. ICP-MS, conducted at Brooks Applied Labs (Bothell, WA), was used to determine metal concentrations found in the supernatant. Results. A Kurskal-Wallis test and Tukey test were used to compare the groups in Table 2 (medium only, IFNy/LPS 20K, medium 20K cells, medium 40K cells). On stainless steel, both non-activated and activated cell groups were shown to have a statistically significant increase in metal ion release for Cr, Fe, and Ni (p<0.05) compared to medium only. On Ti, there was a significant increase in Al (<0.001) and decrease in V (p=0.003) among all groups compared to medium. No differences were seen among disk groups on CoCr. No difference was seen among activated and non-activated cells placed on all three types of disks. Discussion. This study was successful in showing that macrophages are capable of affecting the oxide layer of stainless steel and Ti by releasing more components of the oxide surface within 30 days. A significant increase in Cr, Fe, and Ni ion release was realized when cells were cultured on the surface of stainless steel disks for 30 days. A previous study, also involving 316L stainless steel, has shown that osteoclasts cause a greater increase in Cr compared to Ni under similar conditions. Our results show that macrophages lead to a greater increase of Ni ions compared to Cr. This suggest that various cell types may effectively change metal ion release profiles in different ways. Surprisingly, V content decreased when cells were attached to Ti disks, possibly indicating uptake of the V particles into the cells instead of release into the supernatant. No differences where seen among CoCr disk groups, therefore we cannot determine if corrosion is occurring during the 30 period. To get a more accurate representation a longer testing time may be necessary. For any tables or figures, please contact the authors directly

To evaluate the mechanism by which orthopedic implant wear particles induce apoptosis in immature osteoblasts in an in-vitro setting. Stromal cells from femurs of thirty day-old Swiss Webster Mice were isolated, cultured in-vitro, and incubated with orthopedic wear particles in the micrometer size range. After incubation with wear-particles, the cells were assessed for Caspase three expression and activity in the presence or absence of specific inhibitor(s) in order to delineate potential mechanism for cellular changes previously reported. Here we report the induction of caspase three protein expression and activity with incubation of stromal cells with titanium wear particles. Caspase three activity however was not demonstrated to be up regulated in a time dependent manner or at lower concentration of particles (2 x 107 particles/ml). However, there was a significant (P< 0.05) increase in caspase three activity with titanium particle at higher concentration (4 x 107 particles/ml) that was not reversible when the extrinsic arm of the apoptotic pathway was blocked with anti-TNFƒa antibodies. Our previous studies have suggested that aseptic loosening of orthopedic implants may be independent of inflammatory processes, and may be associated with induction of programmed cell death. Our current results would strengthen this idea by demonstrating induction of expression and activity of caspase three involved in apoptosis in cells incubated with wear particles. In addition, titanium wear particles may induce apoptosis through direct cellular effects rather than through the extrinsic TNFƒa pathway. Delineating the mechanism by which wear particles induce apoptosis in immature osteoblasts will allow for the selection and/or development of inhibitors to the process of asceptic loosening by targeting a specific pathway

Infection of orthopaedic implants is a significant problem, with increased antibiotic resistance of adherent ‘biofilm’ bacteria causing difficulties in treatment. We have investigated the in vitro effect of a pulsed electromagnetic field (PEMF) on the efficacy of antibiotics in the treatment of infection of implants. Five-day biofilms of Staphylococcus epidermidis were grown on the tips of stainless-steel pegs. They were exposed for 12 hours to varying concentrations of gentamicin or vancomycin in microtitre trays at 37°C and 5% CO. 2. The test group were exposed to a PEMF. The control tray was not exposed to a PEMF. After exposure to antibiotic the pegs were incubated overnight, before standard plating onto blood agar for colony counting. Exposure to a PEMF increased the effectiveness of gentamicin against the five-day biofilms of Staphylococcus epidermidis. In three of five experiments there was reduction of at least 50% in the minimum biofilm inhibitory concentration. In a fourth experiment there was a two-log difference in colony count at 160 mg/l of gentamicin. Analysis of variance (ANOVA) confirmed an effect by a PEMF on the efficacy of gentamicin which was significant at p < 0.05. There was no significant effect with vancomycin

Many orthopaedic procedures require implants to be trialled before definitive implantation. Where this is required, the trials are provided in a set with the instrumentation. The most common scenario this is seen in during elective joint replacements. In Scotland (2007) the Scottish Executive (. http://www.sehd.scot.nhs.uk/cmo/CMO(2006)13.pdf. ) recommended and implemented individually packed orthopaedic implants for all orthopaedic sets. The premise for this was to reduce the risk of CJD contamination and fatigue of implants due to constant reprocessing from corrosion. During many trauma procedures determining the correct length of plate or size of implant can be challenging. Trials of trauma implants is no longer common place. Many implants are stored in closed and sealed boxes, preventing the surgeon looking at the implant prior to opening and contaminating the device. As a result many implants are incorrectly opened and either need reprocessed or destroyed due to infection control policy, thus implicating a cost to the NHS. With even the simplest implants costing several hundreds of pounds, this cost is a very significant waste in resources that could be deployed else where. My project was to develop a method to produce in department accurate, cheap and disposable trials for implants often used in trauma, where the original manufacturer do not offer the option of a trial off the shelf. The process had to not involve contaminating or destroying the original implant in the production of a trial. Several implants which are commonly used within Glasgow Royal Infirmary and do not have trials were identified. These implants were then CT scanned within their sealed and sterile packaging without contamination. Digital 3D surface renders of the models were created using free open source software (OsiriX, MeshLab, NetFabb). These models were then processed in to a suitable format for 3D printing using laser sintering via a cloud 3D printing bureau (. Shapeways.com. ). The implants were produced in polyamide PA220 material or in 316L stainless steel. These materials could be serialized using gamma irradiation or ethylene oxide gas. The steel models were suitable for autoclaving in the local CSSU. The implants produced were accurate facsimiles of the original implant with dimensions within 0.7mm. The implants were cost effective, an example being a rim mesh was reproduced in polyamide PA220 plastic for £3.50 and in 316L stainless steel for £15. The models were produced within 10 days of scanning. The stainless steel trials were durable and suitable for reprocessing and resterilisation. The production of durable, low cost and functional implant trials all completed in department was successful. The cost of production of each implant is so low that it would be offset if just one incorrect implant was opened during a single procedure. With some of the implants tested, the trials would have paid for themselves 100 times. This is a simple and cost saving technique that would help reduce department funding and aid patient care

Summary. Staphylococcus aureus isolates from Fracture fixation device related infections contained fewer isolates that form a strong biofilm in comparison with isolates from Prosthetic joint infections. Both orthopaedic implant related infection groups possessed fnbB and sdrE more frequently than the non-implant related infection groups. Introduction. One of the most common pathogen causing musculoskeletal infections is Staphylococcus aureus. The aim was to characterise S. aureus isolated from these infections and to look for differences between the isolates from orthopaedic implant related infections (OIRI) and those in non-implant related infections (NIRI). The OIRI are further differentiated in those associated with fracture fixation (FFI) devices and those found in prosthetic joint infections (PJI). Methods. Three-hundred and five S. aureus isolates were collected from different Swiss and French hospitals (FFI, n=112; PJI, n=105; NIRI, n=88). The cases of NIRI were composed of 27 osteomyelitis (OM), 23 diabetic foot infections (DFI), 27 soft tissue infections (STI) and 11 postoperative spinal infections (SI). Isolates were tested for their ability to form a biofilm. They were typed by agr (accessory gene regulator) group and genes coding for the 13 most relevant MSCRAMMs, Panton-Valentine leukocidin (PVL), PIA (polysaccharide intercellular adhesin), γ-haemolysin, the five most relevant Staphylococcal enterotoxins (SEA-SEE), exfoliative toxins A and B (ETA and ETB) and toxic shock protein (TST) were screened for by PCR. Results. The majority of the S. aureus isolates were methicillin susceptible (MSSA) with 83.4% for the OIRI and 93.2% for the NIRI. All isolates were able to produce a biofilm. A strong biofilm was produced in 13.8% of the OIRI isolates compared to 10.2% of the NIRI isolates. The difference between the isolates of the PJI versus the FFI was statistically significant (20% vs 8%; p=0.011). All four agr types were present in all groups. agrI predominated in the OIRI (42.4%) as well as in the NIRI (44.4%). Comparing OIRI with NIRI, agrII was present in a higher prevalence in OIRI (30.9% vs 14.8%) and agrIII in a lower incidence (21.2% vs 30.7%). Genes cna, clfA and bbp were exhibited predominantly by isolates from the NIRI, while the fnbB and the sdrE gene were more frequently observed among OIRI. Conclusions. Methicillin susceptible S. aureus (MSSA) was more prevalent than methicillin resistant S. aureus (MRSA) in this collection. Possible trends for the orthopaedic device associated infection groups FFI and PJI could be observed whereby isolates from PJI produced stronger biofilm than isolates from the FFI group. The agr type agrII, the fnbB gene and sdrE gene were more prevalent present in the OIRI compared to the NIRI. In contrast, agrIII, and the bbp gene were more prevalent in the NIRI than in the OIRI

Many orthopaedic procedures require implants to be trialled before definitive implantation. Where this is required, the trials are provided in a set with the instrumentation. The most common scenario this is seen in during elective joint replacements. In Scotland (2007) the Scottish Executive (. http://www.sehd.scot.nhs.uk/cmo/CMO(2006)13.pdf. ) recommended and implemented individually packed orthopaedic implants for all orthopaedic sets. The premise for this was to reduce the risk of CJD contamination and fatigue of implants due to constant reprocessing from corrosion. During many trauma procedures determining the correct length of plate or size of implant can be challenging. Trials of trauma implants is no longer common place. Many implants are stored in closed and sealed boxes, preventing the surgeon looking at the implant prior to opening and contaminating the device. As a result many implants are incorrectly opened and either need reprocessed or destroyed due to infection control policy, thus implicating a cost to the NHS. With even the simplest implants costing several hundreds of pounds, this cost is a very significant waste in resources that could be deployed else where. My project was to develop a method to produce in department accurate, cheap and disposable trials for implants often used in trauma, where the original manufacturer do not offer the option of a trial off the shelf. The process had to not involve contaminating or destroying the original implant in the production of a trial. Several implants which are commonly used within Glasgow Royal Infirmary and do not have trials were identified. These implants were then CT scanned within their sealed and sterile packaging without contamination. Digital 3D surface renders of the models were created using free open source software (OsiriX, MeshLab, NetFabb). These models were then processed in to a suitable format for 3D printing using laser sintering via a cloud 3D printing bureau (. Shapeways.com. ). The implants were produced in polyamide PA220 material or in 316L stainless steel. These materials could be serialized using gamma irradiation or ethylene oxide gas. The steel models were suitable for autoclaving in the local CSSU. The implants produced were accurate facsimiles of the original implant with dimensions within 0.7mm. The implants were cost effective, an example being a rim mesh was reproduced in polyamide PA220 plastic for £3.50 and in 316L stainless steel for £15. The models were produced within 10 days of scanning. The stainless steel trials were durable and suitable for reprocessing and resterilisation. The production of durable, low cost and functional implant trials all completed in department was successful. The cost of production of each implant is so low that it would be offset if just one incorrect implant was opened during a single procedure. With some of the implants tested, the trials would have paid for themselves 100 times. This is a simple and cost saving technique that would help reduce department funding and aid patient care

Device-associated bacterial infections are a major and costly clinical challenge. This project aimed to develop a smart new biomaterial for implants that helps to protect against infection and inflammation, promote bone growth, and is biodegradable. Gallium (Ga) doped strontium-phosphate was coated on pure Magnesium (Mg) through a chemical conversion process. Mg was distributed in a graduated manner throughout the strontium-phosphate coating GaSrPO4, with a compact structure and a Ga-rich surface. We tested this sample for its biocompatibility, effects on bone remodeling and antibacterial activities including Staphylococcus aureus, S. epidermidis and E. coli - key strains causing infection and early failure of the surgical implantations in orthopaedics and trauma. Ga was distributed in a gradient way throughout the entire strontium-phosphate coating with a compact structure and a gallium-rich surface. The GaSrPO4 coating protected the underlying Mg from substantial degradation in minimal essential media at physiological conditions over 9 days. The liberated Ga ions from the coatings upon Mg specimens inhibited the growth of bacterial tested. The Ga dopants showed minimal interferences with the SrPO4 based coating, which boosted osteoblasts and undermined osteoclasts in in vitro co-cultures model. The results evidenced this new material may be further translated to preclinical trial in large animal model and towards clinical trial. Acknowledgements: Authors are grateful to the financial support from the Australian Research Council through the Linkage Scheme (ARC LP150100343). The authors acknowledge the facilities, and the scientific and technical assistance of the RMIT University and John Curtin School of Medical Research, Australian National University

By modifying only the nanofeatures on material surfaces without changing surface chemistry, it is possible to increase tissue growth of any human tissue by controlling the endogenous adsorption of adhesive proteins onto the material surface. In addition, our group has shown that these same nanofeatures and nano-modifications can reduce bacterial growth without using antibiotics, which may further accelerate the growth of antibiotic resistant microbes. Inflammation can also be decreased through the use of nanomaterials. Finally, nanomedicine has been shown to stimulate the growth and differentiation of stem cells, which may someday be used to treat incurable disorders, such as neural damage. This strategy also accelerates FDA approval and commercialization efforts since new chemistries are not proposed, rather chemistries already approved by the FDA with altered nanoscale features. This invited talk will highlight some of the advancements and emphasize current ceramic nanomaterials approved by the FDA for human implantation. It will also emphasize the future of nanomaterials in medicine, such as their use in personalized medicine as internal sensors to detect and fight alterations in health.

Aims

This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys.

The aim of this study was to evaluate whether coating titanium discs with selenium in the form of sodium selenite decreased bacterial adhesion of Staphylococcus aureus and Staph. epidermidis and impeded osteoblastic cell growth.

In order to evaluate bacterial adhesion, sterile titanium discs were coated with increasing concentrations of selenium and incubated with bacterial solutions of Staph. aureus (ATCC 29213) and Staph. epidermidis (DSM 3269) and stained with Safranin-O. The effect of selenium on osteoblastic cell growth was also observed. The adherence of MG-63 cells on the coated discs was detected by staining with Safranin-O. The proportion of covered area was calculated with imaging software.

The tested Staph. aureus strain showed a significantly reduced attachment on titanium discs with 0.5% (p = 0.011) and 0.2% (p = 0.02) selenium coating. Our test strain from Staph. epidermidis showed a highly significant reduction in bacterial adherence on discs coated with 0.5% (p = 0.0099) and 0.2% (p = 0.002) selenium solution. There was no inhibitory effect of the selenium coating on the osteoblastic cell growth.

Selenium coating is a promising method to reduce bacterial attachment on prosthetic material.

Cite this article: Bone Joint J 2013;95-B:678–82.

The development and pre-clinical evaluation of nano-texturised, biomimetic, surfaces of titanium (Ti) implants treated with titanium dioxide (TiO₂) nanotube arrays is reviewed. In vitro and in vivo evaluations show that TiO₂ nanotubes on Ti surfaces positively affect the osseointegration, cell differentiation, mineralisation, and anti-microbial properties. This surface treatment can be superimposed onto existing macro and micro porous Ti implants creating a surface texture that also interacts with cells at the nano level. Histology and mechanical pull-out testing of specimens in rabbits indicate that TiO₂ nanotubes improves bone bonding nine-fold (p = 0.008). The rate of mineralisation associated with TiO₂ nanotube surfaces is about three times that of non-treated Ti surfaces. In addition to improved osseointegration properties, TiO₂ nanotubes reduce the initial adhesion and colonisation of Staphylococcus epidermidis. Collectively, the properties of Ti implant surfaces enhanced with TiO₂ nanotubes show great promise.

Cite this article: Bone Joint J 2018;100-B(1 Supple A):9–16.

Aims: Hydroxyapatite coatings have been proven to improve the osteointegration of metal implants however they are not stable and they might delaminate from the metal surface when challenged by the mechanical stresses experienced by the implant. Therefore, efforts of different researchers are being devoted to find more stable coatings or surface treatments that could replace HA.

In particular, spontaneous calcium phosphate deposition on titanium surfaces from aqueous electrolyte containing calcium and phosphate ions, such as simulated body fluid solutions, has been observed and is believed to be related to the excellent bonding capability in contact with bone tissue.

In the present study, a new multiphase anodic spark deposition (ASD) method combined with chemical etching is presented It has been optimized and such modified titanium surface exhibited high mineralisation potential, selective protein adsorption, quicker and more intensive osteoblasts adhesion and differentiation. Such treatements was labelled BioSpark™ and consisted in a thick calcium-phosphate-doped oxide film growth on the titanium bulk. This oxide layer exhibits anatase lattice, micro-porosity and a thin nano-roughened texture.

Methods: The effect of this process, was investigated invitro and in vivo in cortical and spongy bone of 12 adult sheep. Histomorphometric and microhardness measurement were carried out at each experimental time (4, 8, 12 weeks) to quantify the bone-to-implant contact around the implants, the bone ingrowth as well as the newly bone hardness and bone maturation index

Results: Data suggests that the BioSpark treatment produces a modification of the Ti surface, which represents good bioactivity and may be suitable for achieving a stable implant osseointegration.

Conclusions: Such surface modification treatments was applied in the last two years on dental implants with great success and is now being tested in human being for histological studies. In the future, it will be applied on orthopaedic prostheses devices in order to improve device osteintegration. The data demonstrate that this type of surface improves the material osteointegration potential when compared to conventional surfaces while offering high mechanical stability.

Background

Recent advances in materials and manufacturing processes for arthroplasty have allowed fabrication of intricate implant surfaces to facilitate bony attachment. However, refinement and evaluation of these new design strategies is hindered by the cost and complications of animal studies, particularly during early iterations in development process. To address this problem, we have constructed and validated an ex-vivo bone bioreactor culture system to enable empirical testing of candidate structures and materials. In this study, we investigated mineralization of a titanium wire mesh scaffold under both static and dynamic culturing using our ex vivo bioreactor system.

Prosthetic joint infection (PJI) is a serious complication following joint replacement. Antiseptic solutions are often used for intraoperative wound irrigation particularly in cases of revision for PJI. Antiseptic irrigation is intended to eradicate residual bacteria which may be either free floating or in residual biofilm although there is no clear clinical efficacy for its use. Also, reviewing the scientific literature there is discordance in in vitro results where some studies questions antiseptic efficacy whilst others suggest that even at low concentration antiseptic agents are effective at eradicating bacterial biofilms.

The aim of this in vitro study was to establish the efficacy of undiluted antiseptic agents at eradication of a typical PJI forming biofilm and determine the importance of an antiseptic neutralisation step in this assessment.

Mature Staphylococcus epidermidis biofilms grown on TiAl6V4 discs were submerged in chlorohexidine (CHL) gluconate 4%, povidone-iodine (PI) 10% or phosphate-buffered saline (PBS) control solution. The discs were then rinsed, the biofilm bacteria suspended in solution using sonication and vortexing, and the viable count (CFU/ml) of the bacterial suspensions determined. The rinse/suspension solution was either (a) PBS or (b) Dey-Engley neutralization broth (NB).

When PBS was used to rinse/suspend the biofilm a highly significant, 7.5 and 4.1, mean log reduction in biofilm vitality was observed from the control, for CHL 4% and PI 10%, respectively. However, when NB was the rinse/suspension solution the apparent antiseptic biofilm eradication efficacy was replaced with a statistically significant but clinically irrelevant less the one log-reduction in biofilm vitality.

Clinical antiseptic agents are ineffective at eradicating S. epidermidis biofilm in an in vitro PJI model and absence of a neutralisation step gives the false impression of efficacy. Antiseptics alone are an ineffective treatment for biofilm related PJI and no substitute for meticulous debridement.

Aims

Implant waste during total hip arthroplasty (THA) represents a significant cost to the USA healthcare system. While studies have explored methods to improve THA cost-effectiveness, the literature comparing the proportions of implant waste by intraoperative technology used during THA is limited. The aims of this study were to: 1) examine whether the use of enabling technologies during THA results in a smaller proportion of wasted implants compared to navigation-guided and conventional manual THA; 2) determine the proportion of wasted implants by implant type; and 3) examine the effects of surgeon experience on rates of implant waste by technology used.

Aim. Following clean (class I, not contaminated) surgical procedures, the rate of surgical site infection (SSI) should be less than approximately 2%. However, an infection rate of 12.2% has been reported following removal of orthopedic implants used for treatment of fractures below the knee. The objective of this trial was to evaluate the effect of a single dose of preoperative antibiotic prophylaxis on the incidence of SSIs following removal of orthopedic implants used for treatment of fractures below the knee. Method. This multicenter, double-blind, randomized clinical trial included 500 patients from 19 hospitals with a follow-up of 6 months. Eligible were patients aged 18 to 75 years with previous surgical treatment for fractures below the knee who were undergoing removal of orthopedic implants. Exclusion criteria were an active infection or fistula, antibiotic treatment, reimplantation of osteosynthesis material in the same session, allergy for cephalosporins, known kidney disease, immunosuppressant use, or pregnancy. The intervention was a single preoperative intravenous dose of 1000 mg of cefazolin (cefazolin group, n = 228) or sodium chloride (0.9%; saline group, n = 242). Primary outcome was SSI within 30 days as measured by the criteria from the US Centers for Disease Control and Prevention. Secondary outcome measures were functional outcome, health-related quality of life, and patient satisfaction. Results. Among 477 randomized patients (mean age, 44 years [SD, 15]; women, 274 [57%]; median time from orthopedic implant placement, 11 months [interquartile range, 7–16]), 470 patients completed the study. Sixty-six patients developed an SSI (14.0%): 30 patients (13.2%) in the cefazolin group vs 36 in the saline group (14.9%) (absolute risk difference, −1.7 [95% CI, −8.0 to 4.6], P = .60). Conclusions. In patients undergoing surgery for removal of orthopedic implants used for treatment of fractures below the knee, a single preoperative dose of intravenous cefazolin compared with placebo did not reduce the risk of surgical site infection within 30 days following implant removal

Orthopaedic and trauma implant related infection remains one of the major complications that negatively impact clinical outcome and significantly increase healthcare expenditure. Hydroxyapatite has been used for many years to increase implant osseointegration. Silver has been introduced into hydroxyapatite as an antimicrobial coating for orthopedic implants. This surface coatings can both increase tissue compatibility and prevent implant-related infections. We examined infection markers and blood silver values, liver and kidney function tests of 30 patients with of three groups of orthopedic implants, external fixators, intramedullary nails and hip replacements, coated with Ag + ion doped CaP based ceramic powder to determine safety and effectiveness of this dual-function coating. During 1 year follow-up, the pin sites were observed at the external fixator group, and wound areas for the proximal femoral nail and hip arthroplasty group at regular intervals. In addition, liver and kidney function tests, infection markers and blood silver values were checked in patients. In the external fixator group, only 4 out of 91 pin sites (%4.39) were infected. The wound areas healed without any problem in patients with proximal femoral nails and hip arthroplasty. There was no side effect suggesting silver toxicity such as systemic toxic side effect or argyria in any patient and blood silver level did not increase. Compared to similar patient groups in the literature, much lower infection rates were obtained (p = 0.001), and implant osseointegration was good. In patients with chronic infection, the implants were applied acutely after removing the primary implant and with simple debridement. Unlike other silver coating methods, silver was trapped in hydroxyapatite crystals in the ionic form, which is released from the coating during the process of osseointegration, thus, the silver was released into the systemic circulation gradually that showed antibacterial activity locally. We conclude that the use of orthopedic implants with a silver ion added calcium phosphate-based special coating is a safe method to prevent the implant-related infection. This work was supported by TUBİTAK Project Number 315S101

OSSTEC is a pre-spin-out venture at Imperial College London seeking industry feedback on our orthopaedic implants which maintain bone quality in the long term. Existing orthopaedic implants provide successful treatment for knee osteoarthritis, however, they cause loss of bone quality over time, leading to more dangerous and expensive revision surgeries and high implant failure rates in young patients. OSSTEC tibial implants stimulate healthy bone growth allowing simple primary revision surgery which will provide value for all stakeholders. This could allow existing orthopaedics manufacturers to capture high growth in existing and emerging markets while offering hospitals and surgeons a safer revision treatment for patients and a 35% annual saving on lifetime costs. For patients, our implant technology could mean additional years of quality life by revising patients to a primary TKA before full revision surgery. Our implants use patent-filed additive manufacturing technology to restore a healthy mechanical environment in the proximal tibia; stimulating long term bone growth. Proven benefits of this technology include increased bone formation and osseointegration, shown in an animal model, and restoration of native load transfer, shown in a human cadaveric model. This technology could help capture the large annual growth (24%) currently seen in the cementless knee reconstruction market, worth $1.2B. Furthermore, analysis suggests an additional market of currently untreated younger patients exists, worth £0.8B and growing by 18% annually. Making revision surgery and therefore treatment of younger patients easier would enable access to this market. We aim to offer improved patient treatment via B2B sales of implants to existing orthopaedic manufacturer partners, who would then provide them with instrumentation to hospitals and surgeons. Existing implant materials provide good options for patient treatments, however OSSTEC's porous titanium structures offer unique competitive advantages; combining options for modular design, cementless fixation, initial bone fixation and crucially long term bone maintenance. Speaking to surgeons across global markets shows that many surgeons are keen to pursue bone preserving surgeries and the use of porous implants. Furthermore, there is a growing demand to treat young patients (with 25% growth in patients younger than 65 over the past 10 years) and to use cementless knee treatments, where patient volume has doubled in the past 4 years and is following trends in hip treatments. Our team includes engineers and consultant surgeons who have experience developing multiple orthopaedic implants which have treated over 200,000 patients. To date we have raised £175,000 for the research and development of these implants and we hope to gain insight from industry professionals before further development towards our aim to begin trials for regulatory approval in 2026. OSSTEC implants provide a way to stimulate bone growth after surgery to reduce revision risk. We hope this could allow orthopaedic manufactures to explore high growth markets while meaning surgeons can treat younger patients in a cost effective way and add quality years to patients' lives

Aim. In the current study we aim to characterize the use of cationic host defense peptides (HDPs) as alternative antibacterial agents to include into novel antibacterial coatings for orthopedic implants. Staphyloccous aureus represent one the most challenging cause of infections to treat by traditional antibacterial therapies. Thanks to their lack of microbial resistance described so far, HDPs represent an attractive therapeutic alternative to antibiotics. Furthermore, HDPs have been showed to control infections via a dual function: direct antimicrobial activity and regulation of immune response. However, HDPs functions characterization and comparison is controversial, as changing test conditions or cell type used might yield different effects from the same peptide. Therefore, before moving towards the development of HDP-based coatings, we need to characterize and compare the immunomodulatory and antibacterial functions under the same conditions in vitro of 3 well-known cathelicidins: human LL-37, chicken CATH-2, and bovine-derived IDR-1018. Method. S. aureus, strain SH1000, was incubated with different concentrations of each HDP and bacterial growth was monitored overnight. Primary human monocytes were isolated from buffy coats using Ficoll-Paque density and CD14 microbeads, and differentiated for 7 days to macrophages. After 24h incubation in presence of LPS and HDPs, macrophages cytokines production was measured by ELISA. Macrophages cultured for 24h in presence of HDPs were infected with serum-opsonized S. aureus. 30 min and 24h after infection, bacterial phagocytosis and intracellular killing by macrophages were measured by flow cytometry and colony forming units (CFU) count respectively. Results. All HDPs efficiently inhibit macrophages LPS-mediated activation, as observed by a reduced production of TNF-α and IL-10. Despite a comparable anti-inflammatory action, only CATH-2 shows direct antibacterial properties at concentrations 10-times lower than those needed to stimulate immune cells. Although stimulation with HDPs fails to improve macrophages ability to kill intracellular S. aureus, IDR-1018 decreases the proportion of cells phagocytosing bacteria. Conclusions. In addition to a strong anti-inflammatory effect provided by all HDPs tested, CATH-2 has direct antibacterial effects while IDR-1018 reduces the proportion of macrophages infected by S. aureus. Use of these HDPs in combination with each other or with other conventional antibacterial agents could lead the way to the design of novel antibacterial coatings for orthopedic implants

Aim. Prosthetic joint infections pose a major clinical challenge. Developing novel material surface technologies for orthopedic implants that prevent bacterial adhesion and biofilm formation is essential. Antimicrobial coatings applicable to articulating implant surfaces are limited, due to the articulation mechanics inducing wear, coating degradation, and toxic particle release. Noble metals are known for their antimicrobial activity and high mechanical strength and could be a viable coating alternative for orthopaedic implants [1]. In this study, the potential of thin platinum-based metal alloy coatings was developed, characterized, and tested on cytotoxicity and antibacterial properties. Method. Three platinum-based metal alloy coatings were sputter-coated on medical-grade polished titanium discs. The coatings were characterized using optical topography and scanning electron microscopy with energy dispersive spectroscopy (SEM/EDS). Ion release was measured using inductively coupled plasma optical emission spectrometry (ICP-OES). Cytotoxicity was tested according to ISO10993-5 using mouse fibroblasts (cell lines L929 and 3T3). Antibacterial surface activity, bacterial adhesion, bacterial proliferation, and biofilm formation were tested with gram-positive Staphylococcus aureus ATCC 25923 and gram-negative Escherichia coli ATCC 25922. Colony forming unit (CFU) counts, live-dead fluorescence staining, and SEM-EDS images were used to assess antibacterial activity. Results. Three different platinum-based metal alloys consisting of platinum-iridium, platinum-copper, and platinum-zirconium. The coatings were found 80 nm thick, smooth (roughness average < 60 nm), and non-toxic. The platinum-copper coating showed a CFU reduction larger than one logarithm in adherent bacteria compared to uncoated titanium. The other coatings showed a smaller reduction. This data was confirmed by SEM and live-dead fluorescence images, and accordingly, ICP-OES measurements showed low levels of metal ion release from the coatings. Conclusions. The platinum-copper coating showed low anti-adhesion properties, even with extremely low metal ions released. These platinum-based metal alloy coatings cannot be classified as antimicrobial yet. Further optimization of the coating composition to induce a higher ion release based on the galvanic principle is required and copper looks most promising as the antimicrobial compound of choice. Acknowledgments. This publication is supported by the DARTBAC project (with project number NWA.1292.19.354) of the research program NWA-ORC which is (partly) financed by the Dutch Research Council (NWO); and the AMBITION project (with project number NSP20–1-302), co-funded by the PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health to ReumaNederland

Introduction. Orthopedic implants are subject to wear and release ultra-high molecular weight polyethylene (UHMWPE) debris. Analysis of UHMWPE wear particles is critical in determining the safety and effectiveness of novel orthopedic implants. Complete digestion of periprosthetic tissue and wear fluid is necessary to ensure accurate morphological and quantitative particle analysis. Acid digestion methods are more effective than enzymatic and base digestion approaches [Baxter+ 2009]. However, optimal digestion times, quantity, and type of acid are unclear for particle isolation. In addition, imaging and analysis techniques are critical to ensure accurate reporting of particle characteristics. Here, we 1) compared the efficacy of three acid-based digestion methods in isolating particles from a) bovine serum and b) animal/human tissue, and 2) analyzed the effects of imaging location on particle quantity/morphology results. Methods. 1a) UHMWPE (GUR 150) particles were generated by Mode I knee wear testing for 1 million cycles in bovine serum. Serum was digested in one of four solutions: 12.2M HCl, 15.8M HNO. 3. , a 1:1 volume ratio of HNO. 3. :HCl (aqua regia), or filtered H. 2. O (control). The serum:solution volume ratio was 1:5 [Niedzwiecki+ 2001, ISO 17853:2011]. Digestion occurred for 60min on a stir plate at 60°C. Each digest was combined with MeOH at a 1:5 digest:MeOH volume ratio and filtered using a 100 nm polycarbonate membrane. The particle-containing membranes were imaged (12 images/membrane) using scanning electron microscopy (SEM) to determine particle characteristics, including quantity, equivalent circular diameter (ECD) and aspect ratio (AR). 1b) Based on 1a, HNO. 3. was used to digest porcine and human tissue at concentrations of 1:40, 1:60, or 1:80 tissue:HNO. 3. volume ratios for either 1, 12, or 24 hours, followed by SEM analysis. 2) Particle characteristics were compared at nine locations (20 images/location) across a particle-containing membrane to determine the effects of imaging location. Results. 1a) HNO. 3. and aqua regia methods successfully digested the bovine serum, whereas the HCl and H. 2. O methods were unsuccessful (Fig.1A). Comparing HNO. 3. and aqua regia groups, particle characteristics and ECD frequency distribution were nearly identical (Fig.1B). 1b) Nitric acid did not fully digest porcine or human tissues. 2) Similar particle characteristics were observed in all nine locations analyzed across the polycarbonate membrane. The particle quantity, ECD, and AR for a representative center vs. intermediate location were 808 vs. 780 particles, 0.33±0.28 vs. 0.35±0.29 µm, and 1.57±0.56 vs. 1.51±0.4, respectively (Fig.2). Conclusions. Nitric acid and aqua regia are capable of digesting bovine serum using low quantities of acid for short duration, allowing precise analysis of UHMWPE particle debris from orthopedic implants. However, further optimization of digestion techniques for animal/human tissue is warranted. In addition, an accurate representation of particle distribution can be achieved without analyzing hundreds of images, because membrane location does not strongly influence particle results. Finally, ASTM F1877-16 – Standard Practice for Characterization of Particles – could benefit from adding software-based automated particle characterization as an optional method. An automated approach that uses k-means clustering image segmentation to identify particles and computer vision tools to extract relevant morphological features is under development and validation

Aim. Orthopedic implant related surgical site infection (SSI) is a severe complication which represents an important challenge concerning to its treatment. Therefore, gram-negative orthopedic infections have recently become a global concern. Method. Retrospective study through searching of the SCIH (infection control service) database, concerning to the year 2016 and 2017. Cases selected were those of implant placement clean surgeries (osteosynthesis or prosthetic placement) which evolved with SSI and Gram-negative bacterial growth in bone tissue or periprosthetic cultures. Results. During 2016 and 2017, 6150 clean surgeries with orthopedic implant placement were performed; 140 fulfilled SSI criteria (83 cases of open fracture reduction, 44 of hip arthroplasty, 13 of knee arthroplasty). Main agent of infections was Staphylococcus aureus (32,47%) mostly of them methicillin-sensitive (69,20%). However, Gram-negative bacteria were responsible for 64,95% of infections. (Klebsiella pneumoniae 12.8%; Acinetobacter baumannii and Enterobacter ssp 11.96%; Pseudomonas aeruginosa 9.40%) Among them, 100% Enterobacter ssp. were sensitive to carbapenems and 75% to ciprofloxacin. Klebsiella pneumoniae showed sensitivity to carbapenems in 85.7%, Pseudomonas aeruginosa showed sensitivity in 85.7% to carbapenems and 100% to ciprofloxacin. Acinetobacter baumannii showed the least favorable profile amongst Gram-negatives since only 12.5% of strains were sensitive to carbapenems, 28.6% to Ampicilin-sulbactam, 22.2% to ciprofloxacin, while showing 100% sensitivity to polymyxins. 14 patients in whom Acinetobacter baumannii was isolated were predominantly elderly (median 70 years), most of them have underlying/chronic diseases (71.42%) such as diabetes, arterial hypertension, alcoholism, smoking and heart failure. None presented sepsis related to this infection, but four of them died as result of hospitalization related complications (28,60% mortality rate). Among these deaths, 3 were related to total hip arthroplasty, and one to knee arthroplasty. One patient died as result of external causes. Among the survivors, five showed remission/cure. The follow up was lost in 4 patients. Conclusions. SSI caused by carbepenem-resistant Acinetobacter baumannii represents considerable impact on morbi-mortality in patients who undergo surgery with placement of orthopedic implants

Aims. To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections. Methods. EDTA-NS solutions were irrigated at different durations (1, 5, 10, and 30 minutes) and concentrations (1, 2, 5, 10, and 50 mM) to disrupt Staphylococcus aureus biofilms on Matrigel-coated glass and two materials widely used in orthopaedic implants (Ti-6Al-4V and highly cross-linked polyethylene (HXLPE)). To assess the efficacy of biofilm dispersion, crystal violet staining biofilm assay and colony counting after sonification and culturing were performed. The results were further confirmed and visualized by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). We then investigated the efficacies of EDTA-NS irrigation in vivo in rat and pig models of biofilm-associated infection. Results. When 10 mM or higher EDTA-NS concentrations were used for ten minutes, over 99% of S. aureus biofilm formed on all three types of materials was eradicated in terms of absorbance measured at 595 nm and colony-forming units (CFUs) after culturing. Consistently, SEM and CSLM scanning demonstrated that less adherence of S. aureus could be observed on all three types of materials after 10 mM EDTA-NS irrigation for ten minutes. In the rat model, compared with NS irrigation combined with rifampin (Ti-6Al-4V wire-implanted rats: 60% bacteria survived; HXLPE particle-implanted rats: 63.3% bacteria survived), EDTA-NS irrigation combined with rifampin produced the highest removal rate (Ti-6Al-4V wire-implanted rats: 3.33% bacteria survived; HXLPE particle-implanted rats: 6.67% bacteria survived). In the pig model, compared with NS irrigation combined with rifampin (Ti-6Al-4V plates: 75% bacteria survived; HXLPE bearings: 87.5% bacteria survived), we observed a similar level of biofilm disruption on Ti-6Al-4V plates (25% bacteria survived) and HXLPE bearings (37.5% bacteria survived) after EDTA-NS irrigation combined with rifampin. The in vivo study revealed that the biomass of S. aureus biofilm was significantly reduced when treated with rifampin following irrigation and debridement, as indicated by both the biofilm bacterial burden and crystal violet staining. EDTA-NS irrigation (10 mM/10 min) combined with rifampin effectively removes S. aureus biofilm-associated infections both in vitro and in vivo. Conclusion. EDTA-NS irrigation with or without antibiotics is effective in eradicating S. aureus biofilm-associated infection both ex and in vivo. Cite this article: Bone Joint Res 2024;13(1):40–51

An overview about 3D printing technology in orthopaedic applications will be given based on examples. The process from early prototypes to certified implants coming from serial production will be demonstrated also considering relevant surrounding conditions. Today's focus is mostly on orthopaedic implants, but there is a high potential for new implant-related surgical instrument solutions taking into account up-coming clinical demands and user needs accessible by actual 3D printing technologies

Aims. A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database. Methods. Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 374,359 primary THAs with up to 14.5 years' follow-up. We excluded any patients with bilateral THAs, knee arthroplasties, indications other than osteoarthritis, aged under 55 years, and diagnosis of one or more outcome of interest before THA. Implants were grouped as either containing CoCr or not containing CoCr. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined. Results. There were 158,677 individuals (42.4%) with an implant containing CoCr. There were 47,963 deaths, 27,332 heart outcomes, 35,720 cancers, and 22,025 neurodegenerative disorders. There was no evidence of an association between patients with CoCr implants and higher rates of any of the outcomes. Conclusion. CoCr-containing THAs did not have an increased risk of all-cause mortality, or clinically meaningful heart outcomes, cancer, or neurodegenerative disorders into the second decade post-implantation. Our findings will help reassure clinicians and the increasing number of patients receiving primary THA worldwide that the use of CoCr-containing implants is not associated with significant adverse systemic effects. Cite this article: Bone Joint J 2022;104-B(3):359–367

3D-printed orthopedic implants have been gaining popularity in recent years due to the control this manufacturing technique gives the designer over the different design aspects of the implant. This technique allows us to manufacture implants with material properties similar to bone, giving the implant designer the opportunity to address one of the main complications experienced after total hip arthroplasty (THA), i.e. aseptic loosening of the implant. To restore proper function after implant loosening, the implant needs to be replaced. During these revision surgeries, some extra bone is removed along with the implant, further increasing the already present defects, and making it harder to achieve proper mechanical stability with the revision implant. A possible way to limit the increasing loss of bone is the use of biodegradable orthopedic implants that optimize long-term implant stability. These implants need to both optimize the implant such that stress shielding is minimized, and tune the implant degradation rate such that newly formed bone is able to replace the degrading metal in order to maintain a proper bone-implant contact. The hope is that such (partly) degradable implants will lead to a reduction in the size of the bone defects over time, making possible future revisions less likely and less complex. We focused on improving the long-term implant stability of patient-specific acetabular implants for large bone defects and the modeling of their biodegradable behavior. To improve long-term implant stability we implemented a topology optimization approach. A patient-specific finite element model of the hip joint with and without implant was derived from CT-scans to evaluate the performance of the designs during the optimization routine. To evaluate the biodegradation behavior, a quantitative mathematical model was developed to assess the degradation rates of the biodegradable part of the implant. Currently, the biodegradation model has been implemented for magnesium (Mg) implants as a first proof of concept. For a first test case, an optimized implant was found with stress shielding levels below 20% in most regions. The highest stress shielding levels were found at the bone implant interface. The biodegradation model has been validated using experimental data, which includes immersion tests of simple scaffolds created from Commercial Pure Mg. The mass loss of the scaffold is about 0.8 mg/cm. 2. for the first day of immersion in simulated body fluid (SBF) solution. After the formation of a protective film on the surface of the simple scaffold, the degradation rate starts to slow down. Initial results presented serve as a proof of concept of the developed computational framework for the implant optimization and the implant biodegradation behavior. Currently, timing calibration, benchmarking and validation are taking place. Reducing implant-induced stress shielding, obtaining a better implant integration and reduction of bone defects, by allowing for bone to partially replace the implant over time, are crucial design factors for large bone defect implants. In this research, we have developed in-silico models to investigate these factors. Once validated and coupled, the models will serve as an important tool to find the appropriate biodegradable implant designs and biodegradable metal properties for THA applications, that improve current implant lifetime while ensuring proper mechanical functioning

Ti-6Al-4V is the most common alloy used for orthopaedic implants. Its popularity is due to low density, superior corrosion resistance, good osseointegration and lower elastic modulus when compared to other commonly used alloys such as CoCrMo and stainless steel. In fact, the use of Ti64 has even further increased lately since recent controversy around adverse local tissue reactions and implant failure related to taper corrosion of CoCrMo alloy. However, implants made from Ti64 can fail in some cases due to fatigue fracture, sometimes related to oxide induced stress corrosion cracking or hydrogen embrittlement, or preferential corrosion of the beta phase. Studies performed with Ti-6Al-4V do often not consider that the alloy itself may have a range of characteristics that can vary and could significantly impact the implant properties. These variations are related to the material microstructure which depends not only on chemical composition, but also the manufacturing process and subsequent heat treatments. Different microstructures can occur in implants made form wrought alloys, cast alloys, and more recently, additive manufactured (AM) alloys. Implant alloy microstructure drives mechanical and electrochemical properties. Therefore, this study aims to analyse the microstructure of Ti-6Al-4V alloy of additive manufactured and conventional retrieved orthopaedic implants such as acetabular cups, tibial trays, femoral stem and modular neck by means of electron backscatter diffraction (EBSD). Microstructural features of interest include grains shape and size, phase content and distribution, preferred grain orientation (texture), alloying elements distribution (homogenization) and presence of impurities. Additionally, we demonstrate the direct impact of different microstructural features on hardness. We analysed 17 conventional devices from 6 different manufacturers, 3 additive manufactured devices from 2 different manufactures and 1 control alloy (bar stock). The preliminary results showed that even though all implants have the same chemical composition, their microstructural characteristics vary broadly. Ti64 microstructure of conventional alloys could be categorized in 3 groups: equiaxed grains alloys (Fine and Coarse), bimodal alloys and dendritic alloys. The additive manufactured implants were classified in an additional group on its own which consists of a needle-like microstructures - similar to Widmanstätten patterns, Fig. 1, with a network of β phase along α phase grains. Furthermore, AM alloys exhibited residual grain boundaries from the original β grains from the early stage of the solidification process, Fig. 2. These characteristics may have implication on the fatigue and corrosion behaviour. In addition, it we observed inhomogeneous alloying element distribution in some cases, Fig. 3, especially for the additive manufactured alloys, which also may have consequences on corrosion behaviour. Finally, the hardness testing revealed that the implants with large grain size, such as AM alloys, exhibit low hardness values, as expected, but also the amount of beta phase correlated positively with lower hardness. Grain aspect ratio and beta phase grain size correlated positively with higher hardness. In summary, we found that common Ti64 implants can exhibit a broad variety of different alloy microstructures and the advent of AM alloys introduces an entirely new category. It is imperative to determine the ideal microstructure for specific applications

The evolution of orthopedic implants has witnessed a great evolution and allowed insights into the various metals and alloys compatible with the human body. However, some recent reports have raised concerns regarding hypersensitivity to several metals used in orthopedic implants. These cases are mostly documented in the field of arthroplasty. Metal ion release following hip or knee arthroplasty is a known phenomenon and associated immune reactions to these metal ions have been implicated in the causation of these hypersensitivity reactions. These reactions frequently lead to poor outcome following these implant surgeries. We here present two rare cases of metal induced hypersensitivity reactions following orthopedic surgeries. We have also reviewed the literature in this context to look into the various causes of metal reactions, types of implant involved in hypersensitivity, methods of testing and management options in these cases

3D printing and rapid prototyping in surgery is an expanding technology. It is often used for preoperative planning, procedure rehearsal and patient education. There have been recent advances in orthopaedic surgery for the development of patient specific guides and jigs. The logical next step as the technology advances is the production of custom orthopaedic implants. I aimed to use freely available open source software and online cloud 3D printing services to produce a patient specific orthopaedic implant without requiring the input of a university department, specialised equipment or implant companies. Using standard CT scan DICOM data, a 3D surface reconstruction was made of a patient's uninjured radial head using open source DICOM viewer OsiriX. This was then manipulated in other open source software packages called Meshlabs and Netfabb to create a mirror image 3D model of the radial head with a stem to produce a prosthesis suitable to replace the contralateral fractured radial head. This was then uploaded and printed in stainless steel via cloud printing service . Shapeways.com. . The model produced was an exact replication of the patient's original anatomy, except a mirror image suitable for replacement of the contralateral side. The process did not involve any specialist equipment or input from an academic department or implant company. It took a total of 10 days to produce and cost less than £40. From this study I was able to show that production of patient specific orthopaedic implants is possible. It also highlights that the technology is accessible to all, and does not require any special equipment or large investment. It can be achieved quickly and for a very small financial outlay. As a proof of concept it has been very successful

Titanium (Ti) is well known in orthopedic implant materials such as total hip replacement arthroplasty. Osseointegration of orthopedic implants is defined as the formation of a direct interface between the implant and the bone without intervening soft tissue. Unmodified Ti is not sufficient to complete adhesion between Ti surface and host bone with subsequent implant loosening over time and ultimately implant failure. An effective approach to enhance the biological activity of orthopedic implants and improve post-implantation healing is to modify the implant surface. The aim of this study was to investigate the effect of functionalized titanium (Ti) with alendronate (Aln) and bone morphogenic protein-2 (BMP-2) for enhancement of osteoblast activity in vitro. Aln and/or BMP-2 were sequentially immobilized to the heparinized-Ti (Hep-Ti) surface. The compositions of pristine Ti and Hep-Ti with or without Aln and/or BMP-2 were characterized by scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). Osteoblast activities on all Ti substrates were investigated by cell proliferation assays, alkaline phosphate (ALP) activity, calcium deposition, gene expressions of osteocalcin and osteopontin. The modified Ti surface with heparin, Aln, BMP-2 and Aln/BMP-2 showed similar morphologies compared to that of pristine Ti on scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). Aln or BMP-2 from Aln/Hep-Ti, BMP-2/Hep-Ti or Aln/BMP-2/ Hep-Ti substrates exhibited sustained release profiles up to 4 weeks. No significant cytotoxic effects were observed for incubation periods for up to 48 h. the ALP activity of MG-63 cells cultured on Hep-Ti was not significantly different compared to those cultured on pristine Ti for 7, 14, and 21 days. Alkaline phosphatase(ALP) activities of osteoblasts cultured on Ti groups immobilized with Aln, BMP-2, or Aln/BMP-2 were significantly increased when compared to pristine Ti(p < 0.05). Calcium deposition was markedly increased in Aln/BMP-2/Hep-Ti compared to Aln/Hep-Ti or BMP-2/Hep-Ti, respectively (p < 0.05). mRNA expressions of osteocalcin(OCN) and osteopontin(OPN) of osteoblasts grown on Aln/Hep-Ti, BMP-2/Hep-Ti, and Aln/BMP-2/Hep-Ti were significantly higher than of those grown on pristine Ti (p < 0.05). Based on the results of the in vitro studies, we showed that co-delivery of alendronate and BMP-2 had an additive effect on osteoblast activity and mineralization when compared with pristine Ti as well as alendronate or BMP-2 alone. Functionalized Ti systems with alendronate and BMP-2 can give a good solution to solve the most common problems associated with orthopedic and dental implants. Furthermore, in vivo studies required to determine the optimal doses of alendronate and BMP-2 for clinical application

Pulsed electromagnetic fields (PEMFs) have been considered a potential treatment modality for fracture healing. As bone fracture healing and osseointegration share the same biological events, the application of PEMF stimulation to facilitate the osseointegration process of orthopedic implants has been suggested. However, the mechanism of their action remains unclear. Mammalian target of rapamycin (mTOR) signaling may affect osteoblast proliferation and differentiation. This study aimed to assess the osteogenic differentiation of mesenchymal stem cells (MSCs) under PEMF stimulation and the potential involvement of mTOR signaling pathway in this process. PEMFs were generated by a novel miniaturized electromagnetic device (MED). Potential changes in the expression of mTOR pathway components, including receptors, ligands and nuclear target genes, and their correlation with osteogenic markers and transcription factors were analyzed. PEMF exposure increased cell proliferation, adhesion and osteogenic commitment of MSCs. Osteogenic-related genes were over-expressed following PEMF treatment. Our results confirm that PEMFs contribute to activation of the mTOR pathway via upregulation of the proteins AKT, MAPP kinase, and RRAGA, suggesting that activation of the mTOR pathway is required for PEMF-stimulated osteogenic differentiation. In summary, the findings of the present study revealed that MED-generated PEMFs stimulate osteogenic differentiation and the maturation of the adipose tissue-derived MSCs via activation of the mTOR pathways. Even though further research is required to determine an optimal stimulation timing and flux density both in-vitro and in-vivo, this study results may serve a source for an adjuvant therapy to improve orthopedic implant stability, longevity and enhance fracture healing

Biodegradable metals as orthopaedic implant materials receive substantial scientific and clinical interest. Marketed cardiovascular products confirm good biocompatibility of iron. Solid iron biodegrades slowly in vivo and has got supra-physiological mechanical properties as compared to bone and porous implants can be optimized for specific orthopaedic applications. We used Direct Metal Printing (DMP)3 to additively manufacture (AM) scaffolds of pure iron with fine-tuned bone-mimetic mechanical properties and improved degradation behavior to characterize their biocompatibility under static and dynamic 3D culture conditions using a spectrum of different cell types. Atomized iron powder was used to manufacture scaffolds with a repetitive diamond unit cell design on a ProX DMP 320 (Layerwise/3D Systems, Belgium). Mechanical characterization (Instron machine with a 10kN load cell, ISO 13314: 2011), degradation behavior under static and dynamic conditions (37ºC, 5% CO2 and 20% O2) for up of 28 days, with μCT as well as SEM/energy-dispersive X-ray spectroscopy (EDS) (SEM, JSM-IT100, JEOL) monitoring under in vivo-like conditions. Biocompatibility was comprehensively evaluated using a broader spectrum of human cells according to ISO 10993 guidelines, with topographically identical titanium (Ti-6Al-4V, Ti64) specimen as reference. Cytotoxicity was analyzed by two-way ANOVA and post-hoc Tukey's multiple comparisons test (α = 0.05). By μCT, as-built strut size (420 ± 4 μm) and porosity of 64% ± 0.2% were compared to design values (400 μm and 67%, respectively). After 28 days of biodegradation scaffolds showed a 3.1% weight reduction after cleaning, while pH-values of simulated body fluids (r-SBF) increased from 7.4 to 7.8. Mechanical properties of scaffolds (E = 1600–1800 MPa) were still within the range for trabecular bone, then. At all tested time points, close to 100% biocompatibility was shown with identically designed titanium (Ti64) controls (level 0 cytotoxicity). Iron scaffolds revealed a similar cytotoxicity with L929 cells throughout the study, but MG-63 or HUVEC cells revealed a reduced viability of 75% and 60%, respectively, already after 24h and a further decreased survival rate of 50% and 35% after 72h. Static and dynamic cultures revealed different and cell type-specific cytotoxicity profiles. Quantitative assays were confirmed by semi-quantitative cell staining in direct contact to iron and morphological differences were evident in comparison to Ti64 controls. This first report confirms that DMP allows accurate control of interconnectivity and topology of iron scaffold structures. While microstructure and chemical composition influence degradation behavior - so does topology and environmental in vitro conditions during degradation. While porous magnesium corrodes too fast to keep pace with bone remodeling rates, our porous and micro-structured design just holds tremendous potential to optimize the degradation speed of iron for application-specific orthopaedic implants. Surprisingly, the biological evaluation of pure iron scaffolds appears to largely depend on the culture model and cell type. Pure iron may not yet be an ideal surface for osteoblast- or endothelial-like cells in static cultures. We are currently studying appropriate coatings and in vivo-like dynamic culture systems to better predict in vivo biocompatibility

Titanium alloys are one of the most used for orthopaedic implants and the fabrication of them by 3D printing technology is a raising technology, which could effectively resolve existing challenges. Surface modification of Ti surfaces is often necessary to improve biocorrosion resistance, especially in inflammatory conditions. Such modification can be made by coatings based on hydrogels, like alginate (Alg) - a naturally occurring anionic polymer. The properties of the hydrogel can be further enhanced with calcium phosphates like octacalcium phosphate (OCP) as a precursor of biologically formed hydroxyapatite. Formed Alg-OCP matrices have a high potential in wound healing, delivery of bioactive agents etc. but their effect on 3D printed Ti alloys performance was not well known. In this work, Alg-OCP coated 3D printed samples were studied with electrochemical measurements and revealed significant variations of corrosion resistance vs. composition of the coating. The potentiodynamic polarization test showed that the Alg-OCP-coated samples had lower corrosion current density than simple Alg-coated samples. Electrochemical impedance spectroscopy indicated that OCP incorporated hydrogels had also a high value of the Bode modulus and phase angle. Hence Alg-OCP hydrogels could be highly beneficial in protecting 3D printed Ti alloys especially when the host conditions for the implant placement are inflammatory. AcThis work was supported by the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions GA860462 (PREMUROSA). The authors also acknowledge the access to the infrastructure and expertise of the BBCE – Baltic Biomaterials Centre of Excellence (European Union Horizon 2020 programme under GA857287)

Polymethylmethacrylate (PMMA) bone cement is strong in compression, however it tends to fail under torsion. Sufficient pressurisation and subsequent interdigitation between cement and bone are critical for the mechanical interlock of cemented orthopaedic implants, and an irregular surface on the acetabular cup is necessary for reasonable fixation at the cup-cement interface. There is limited literature investigating discrepancies in the failure mechanisms of cemented all-polyethylene acetabular cups with and without cement spacers, under torsional loading. In vitro experimental comparison of three groups of polyethylene acetabular prosthesis (PAP) cemented into prepared sawbone hemipelvises:. * PAP without PMMA spacers maintaining an equal cement mantle circumferentially. (Group 1 n=3). * PAP without PMMA spacers cemented deliberately ‘bottoming-out’ the implant within the acetabulum. (Group 2 n=3). * PAP with PMMA spacers. (Group 3 n=3). The constructs were tested to torstional failure on a custom designed setup, and statistical analysis done by a one-way ANOVA and Tukey-Welsh test. Group 3 demonstrated superior torsional resistance with a statistically significant torque of 145Nm (SD±12Nm) at failure, compared to group 2 (109Nm, SD±7Nm) and group 1 (99Nm, SD±8Nm). Group 3 experienced failure predominantly at the bone-cement interface, in contrast, Groups 1 and 2 exhibited failure predominantly at the cup-cement interface. There was no significant difference between Group 1 and 2. Qualitative analysis of the failure mode indicates the efficient redistribution of stress throughout the cement mantle, consistent with the greater uniformity of cement. PMMA spacers increase the resistance to torsional failure at the implant-cement interface. Acetabular components without spacers (Groups 1 and 2) failed at the implant-cement interface before the cement-bone interface, at a statistically significantly lower level of torque to failure. Although the PMMA spacers may reduce cement interdigitation at the cement-bone interface the torsional forces required to fail are likely supraphysiological

Introduction: The mechanobiology and response of bone formation to strain under physiological loading is well established, however investigation into exceedingly soft scaffolds relative to cancellous bone is limited. In this study we designed and 3D printed mechanically-optimised low-stiffness implants, targeting specific strain ranges inducing bone formation and assessed their biological performance in a pre-clinical in vivo load-bearing tibial tuberosity advancement (TTA) model. The TTA model provides an attractive pre-clinical framework to investigate implant osseointegration within an uneven loading environment due to the dominating patellar tendon force. A knee finite element model from ovine CT data was developed to determine physiological target strains from simulated TTA surgery. We 3D printed low-stiffness Ti wedge osteotomy implants with homogeneous stiffness of 0.8 GPa (Ti1), 0.6 GPa (Ti2) and a locally-optimised design with a 0.3 GPa cortex and soft 0.1 GPa core (Ti3), for implantation in a 12-week ovine tibial advancement osteotomy (9mm). We quantitatively assessed bone fusion, bone area, mineral apposition rate and bone formation rate. Optimised Ti3 implants exhibited evenly high strains throughout, despite uneven wedge osteotomy loading. We demonstrated that higher strains above 3.75%, led to greater bone formation. Histomorphometry showed uniform bone ingrowthin optimised Ti3 compared to homogeneous designs (Ti1 and Ti2), and greater bone-implant contact. The greatest bone formation scores were seen in Ti3, followed by Ti2 and Ti1. Results from our study indicate lower stiffness and higher strain ranges than normally achieved in Ti scaffolds stimulate early bone formation. By accounting for loading environments through rational design, implants can be optimised to improve uniform osseointegration. Design and 3D printing of exceedingly soft titanium orthopaedic implants enhance strain induced bone formation and have significant importance in future implant design for knee, hip arthroplasty and treatment of large load-bearing bone defects

Infection of implanted medical devices (biomaterials), like titanium orthopaedic implants, can have disastrous consequences, including removal of the device. These so-called biomaterial-associated infections (BAI) are mainly caused by Staphylococcus aureus and Staphylococcus epidermidis. To prevent biofilm formation using a non-antibiotic based strategy, we aimed to develop a novel permanently fixed antimicrobial coating for titanium devices based on stable immobilized quaternary ammonium compounds (QACs). Medical grade titanium implants were dip-coated in subsequent solutions of hyperbranched polymer, polyethyleneimine and 10 mM sodium iodide, and ethanol. The QAC-coating was characterized using water contact angle measurements, scanning electron microscopy, FTIR, AFM and XPS. The antimicrobial activity of the coating was evaluated against S. aureus strain JAR060131 and S. epidermidis strain ATCC 12228 using the JIS Z 2801:2000 surface microbicidal assay. Lastly, we assessed the in vivo antimicrobial activity in a mouse subcutaneous implant infection model with S. aureus administered locally on the QAC-coated implants prior to implantation to mimic contamination during surgery. Detailed material characterization of the titanium samples showed the presence of a homogenous and stable coating layer at the titanium surface. Moreover, the coating successfully killed S. aureus and S. epidermidis in vitro. The QAC-coating strongly reduced S. aureus colonization of the implant surface as well as of the surrounding tissue, with no apparent macroscopic signs of toxicity or inflammation in the peri-implant tissue at 1 and 4 days after implantation. An antimicrobial coating with stable quaternary ammonium compounds on titanium has been developed which holds promise to prevent BAI. Non-antibiotic-based antimicrobial coatings have great significance in guiding the design of novel antimicrobial coatings in the present, post-antibiotic era. Acknowledgements: This research was financially supported by the Health∼Holland/LSH-TKI call 2021–2022, project 25687, NACQAC: ‘Novel antimicrobial coatings with stable non-antibiotic Quaternary Ammonium Compounds and photosensitizer technology'

The success of cementless orthopaedic implants relies on bony ingrowth and active bone remodelling. Much research effort is invested to develop implants with controllable surface roughness and internal porous architectures that encourage these biological processes. Evaluation of these implants requires long-term and costly animal studies, which do not always yield the desired outcome requiring iteration. The aim of our study is to develop a cost-effective method to prescreen design parameters prior to animal trials to streamline implant development and reduce live animal testing burden. Ex vivo porcine cancellous bone cylinders (n=6, Ø20×12mm) were extracted from porcine knee joints with a computer-numerically-controlled milling machine under sterile conditions within 4 hours of animal sacrifice. The bone discs were implanted with Ø6×12mm additive manufactured porous titanium implants and were then cultured for 21days. Half underwent static culture in medium (DMEM, 10% FBS, 1% antibiotics) at 37°C and 5% CO. 2. The rest were cultured in novel high-throughput stacked configuration in a bioreactor that simulated physiological conditions after surgery: the fluid flow and cyclic compression force were set at 10ml/min and 10–150 N (1Hz,5000 cycles/day) respectively. Stains were administered at days 7 and 14. Samples were evaluated with widefield microscopy, scanning electron microscopy (SEM) and with histology. More bone remodelling was observed on the samples cultured within the bioreactor: widefield imaging showed more remodelling at the boundaries between the implant-bone interface, while SEM revealed immature bone tissue integration within the pores of the implant. Histological analysis confirmed these results, with many more trabecular struts with new osteoid formation on the samples cultured dynamically compared to static ones. Ex vivo bone can be used to analyse new implant technologies with lower cost and ethical impact than animal trial. Physiological conditions (load and fluid flow) promoted bone ingrowth and remodelling

3D printing is rapidly being adopted by manufacturers to produce orthopaedic implants. There is a risk however of structural defects which may impact mechanical integrity. There are also no established standards to guide the design of bone-facing porous structures, meaning that manufacturers may employ different approaches to this. Characterisation of these variables in final-production implants will help understanding of the impact of these on their clinical performance. We analysed 12 unused, final-production custom-made 3D printed acetabular cups that had been produced by 6 orthopaedic manufacturers. We performed high resolution micro-CT imaging of each cup to characterise the morphometric features of the porous layers: (1) the level of porosity, (2) pore size, (3) thickness of porous struts and (4) the depth of the porous layers. We then examined the internal cup structures to identify the presence of any defects and to characterise: (1) their total number, (2) volume, (3) sphericity, (4) size and (5) location. There was a variability between designs in the level of porosity (34% to 85%), pore size (0.74 to 1.87mm), strut thickness (0.28 to 0.65mm), and porous layer depth (0.57 to 11.51mm). One manufacturer printed different porous structures between the cup body and flanges; another manufacturer printed two differing porous regions within the cup body. 5 cups contained a median (range) of 90 (58–101) defects. The median defect volume was 5.17 (1.05–17.33) mm3. The median defect sphericity and size were 0.47 (0.19–0.65) and 0.64 (0.27–8.82) mm respectively. The defects were predominantly located adjacent to screw holes, within flanges and at the transition between the flange and main cup body; these were between 0.17 and 4.66mm from the cup surfaces. There is a wide variability between manufacturers in the porous titanium structures they 3D print. The size, shape and location of the structural defects identified are such that there may be an increased risk of crack initiation from them, potentially leading to a fracture. Regulators, surgeons, and manufacturers should be aware of this variability in final print quality

Several implants have a proven track record of durability and function in patients over many years. As manufacturers' patents expire it is understandable that cheaper generic copies would be considered. There is currently no established, independent method of determining design equivalence between generic and branded orthopaedic implants. We acquired 10 boxed, as manufactured components consisting of the generic OptiStem XTR model (n=5) and branded Exeter (n=5) femoral stems. Two examiners were blinded to the implant design and independently measured the mass, volume, trunnion surface topography, roughness, trunnion cone angle, CCD angle and femoral offset using peer-reviewed methods. We then compared the stems using these parameters. We found that the OptiStems (1) were lighter (p<0.001) (2) had a rougher trunnion surface (p<0.001) with a greater spacing and depth of the machined threads (p<0.001), (3) had greater trunnion cone angles (p=0.007) and (4) a smaller radius at the top of the trunnion (p=0.007). There was no difference for stem volume (p=0.643), CCD angle (p=0.788) or offset (p=0.993). This study is the first independent investigation of the equivalence of a generic orthopaedic implant to its branded design. We found a clear difference in trunnion roughness, trunnion cone angle and radius, and implant mass when comparing the two generic and branded stem designs. All implants require standard regulatory processes to be followed. It does not appear feasible that generic implants can be manufactured to predictability guarantee the same performance as generic drugs. We found a number of physical differences between the generic and branded implants. Whilst both designs are likely to work in clinical practice, they are different

Introduction:. While indications for total knee (TKA) and hip arthroplasty (THA) have expanded over the last 35 years, implant labeling has largely remained stagnant, with conditions including obesity, developmental dysplasia, and many others (Table 1) still considered as contraindications. Implant labeling has not co-evolved with surgical indications, as most orthopaedic implants are cleared through the 510(k) process, which conserves the labeling of the predicate device. While surgeons can legally use devices for off-label indications, the scrutiny regarding off-label use of orthopaedic implants has intensified. The objective of this study was to determine the incidence of off-label use at our institution, define the risk in terms of revision rate associated with off-label use, and to compare activity level, functional outcomes, and general health outcomes for on- and off-label TKA and THA patients. Methods:. Patients who underwent primary TKA or THA at a large academic tertiary referral center between January 1, 2010 and June 30, 2010 were considered for the study (n = 705). Of this cohort, a convenience sample of 283 patients were selected for the study based on the presence of baseline outcomes data. Patients were contacted via mail and/or phone to collect details regarding potential revision surgeries, UCLA activity scores, short form-12 (SF-12), Knee Injury and Osteoarthritis Outcome Score (KOOS) or Hip Disability and Osteoarthritis Outcome Score (HOOS). Using labeled contraindications from the product inserts from multiple orthopaedic implant manufacturers, procedures were categorized as on-label or off-label. Outcomes including revision rate, activity score, and SF-12, KOOS, and HOOS scores were adjusted for age, gender, and BMI by fitting a logistic model and analyzed using the Wald chi-square test (SPSS, Chicago, IL). Results:. 225 patients responded to the survey (79.5% follow-up), with an average follow-up of 2.4 years (± 0.24). Demographics, including age (p = 0.07) and gender (p = 0.31), were not significantly different between the 2 groups. Since obesity was a contraindication, the off-label group was significantly heavier (mean BMI = 34.0) than the on-label group (mean BMI = 26.0; p < 0.001). The overall rate of cases defined as off-label was 68.4% (154/225), the majority of which were due to obesity (118/154; 76.6%), followed by patients who used steroids, immunosuppressive drugs, or diabetes medication (37/154; 24.0%). Adjusting for age, gender, and BMI, the revision rate for on-label (4/71; 5.6%) compared with off-label (11/154; 7.1%) was not significantly different (p = 0.62). Adjusted UCLA activity scores were not significantly different between on-label (5.9 ± 2.0) and off-label (5.7 ± 2.0) patients (p = 0.56). When comparing the adjusted improvements (i.e. difference between preoperative and postoperative) in SF-12, KOOS, and HOOS scores, only the SF-12 role physical subscore was statistically lower for off-label patients (Table 2; p = 0.03). Discussion:. These pilot data suggest that on- and off-label use of THA and TKA implants result in similar short-term revision rates, activity levels, and functional and general health outcomes. In addition, the improvements realized by off-label patients, as reflected by SF-12 composite scores and KOOS/HOOS quality of life, support the use of these devices in previously contraindicated conditions, with no discernible increased risk of revision

Aim. The use of medical devices has grown significantly over the last decades, and has become a major part of modern medicine and our daily life. Infection of implanted medical devices (biomaterials), like titanium orthopaedic implants, can have disastrous consequences, including removal of the device. For still not well understood reasons, the presence of a foreign body strongly increases susceptibility to infection. These so-called biomaterial-associated infections (BAI) are mainly caused by Staphylococcus aureus and Staphylococcus epidermidis. Formation of biofilms on the biomaterial surface is generally considered the main reason for these persistent infections, although bacteria may also enter the surrounding tissue and become internalized within host cells. To prevent biofilm formation using a non-antibiotic based strategy, we aimed to develop a novel permanently fixed antimicrobial coating for titanium devices based on stable immobilized quaternary ammonium compounds (QACs). Method. Medical grade titanium implants (10×4×1 mm) were dip-coated in a solution of 10% (w/v) hyperbranched polymer, subsequently in a solution of 30% (w/v) polyethyleneimine and 10 mM sodium iodide, using a dip-coater, followed by a washing step for 10 min in ethanol. The QAC-coating was characterized using water contact angle measurements, scanning electron microscopy, FTIR, AFM and XPS. The antimicrobial activity of the coating was evaluated against S. aureus strain JAR060131 and S. epidermidis strain ATCC 12228 using the JIS Z 2801:2000 surface microbicidal assay. Lastly, we assessed the in vivo antimicrobial activity in a mouse subcutaneous implant infection model with S. aureus administered locally on the QAC-coated implants prior to implantation to mimic contamination during surgery. Results. Detailed material characterization of the titanium samples showed the presence of a homogenous and stable coating layer at the titanium surface. Moreover, the coating successfully killed S. aureus and S. epidermidis in vitro. The QAC-coating strongly reduced S. aureus colonization of the implant surface as well as of the surrounding tissue, with no apparent macroscopic signs of toxicity or inflammation in the peri-implant tissue at 1 and 4 days after implantation. Conclusions. An antimicrobial coating with stable quaternary ammonium compounds on titanium has been developed which holds promise to prevent BAI. Non-antibiotic-based antimicrobial coatings have great significance in guiding the design of novel antimicrobial coatings in the present, post-antibiotic era

Aims. Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods. A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 10. 5. colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results. The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log. 10. (95%) and 1.5-log. 10. (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 10. 3. vs 7.0 × 10. 4. ; p = 0.022; 3.6 × 10. 3. vs 1.0 × 10. 5. ; p = 0.007, respectively) at POD 21. There was a significant 1.6-log. 10. (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 10. 0. vs 4.7 × 10. 1. , respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion. In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections. Cite this article: Bone Joint J 2024;106-B(6):632–638