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

Aims. BoneMaster is a thin electrochemically applied hydroxyapatite (HA) coating for orthopaedic implants that is quickly resorbed during osseointegration. Early stabilization is a surrogacy marker of good survival of femoral stems. The hypothesis of this study was that a BoneMaster coating yields a fast early and lasting fixation of stems. Methods. A total of 53 patients were randomized to be treated using Bi-Metric cementless femoral stems with either only a porous titanium plasma-sprayed coating (P group) or a porous titanium plasma-sprayed coating with an additional BoneMaster coating (PBM group). The patients were examined with radiostereometry until five years after surgery. Results. At three months, the mean total translation (TT) was 0.95 mm (95% confidence interval (CI) 0.68 to 1.22) in the P group and 0.57 mm (95% CI 0.31 to 0.83) in the PBM group (p = 0.047). From two to five years, the TT increased by a mean of 0.14 mm (95% CI 0.03 to 0.25) more in the P group than in the PBM group (p = 0.021). In osteopenic patients (n = 20), the mean TT after three months was 1.61 mm (95% CI 1.03 to 2.20) in the P group and 0.73 mm (95% CI 0.25 to 1.21) in the PBM group (p = 0.023). After 60 months, the mean TT in osteopenic patients was 1.87 mm (95% CI 1.24 to 2.50) in the P group and 0.82 mm (95% CI 0.30 to 1.33) in the PBM group (p = 0.011). Conclusion. There was less early and midterm migration of cementless stems with BoneMaster coating compared with those with only a porous titanium plasma-sprayed coating. Although a BoneMaster coating seems to be important for stem fixation, especially in osteopenic patients, further research is warranted. Cite this article: Bone Joint J 2022;104-B(6):647–656

Aims. Short, bone-conserving femoral components are increasingly used in total hip arthroplasty (THA). They are expected to allow tissue-conserving implantation and to render future revision surgery more straightforward but the long-term data on such components is limited. One such component is the global tissue-sparing (GTS) stem. Following the model for stepwise introduction of new orthopaedic implants, we evaluated early implant fixation and clinical outcome of this novel short-stem THA and compared it to that of a component with established good long-term clinical outcome. Methods. In total, 50 consecutive patients ≤ 70 years old with end-stage symptomatic osteo-arthritis were randomized to receive THA with the GTS stem or the conventional Taperloc stem using the anterior supine intermuscular approach by two experienced hip surgeons in two hospitals in the Netherlands. Primary outcome was implant migration. Patients were followed using routine clinical examination, patient reported outcome using Harris Hip Score (HHS), Hip Disability And Osteoarthritis Outcome Score (HOOS), EuroQol five-dimension questionnaire (EQ5D), and Roentgen Stereophotogrammetric Analysis (RSA) at three, six, 12, and 24 months. This study evaluated the two-year follow-up results. Results. In addition to the initial migration pattern of distal migration (subsidence, Y-translation) and retroversion (Y-rotation) also exhibited by the Taperloc stem, the GTS stem showed an initial migration pattern of varization (X-translation combined with Z-rotation) and posterior translation (Z-translation). However, all components stabilized aside from one Taperloc stem which became loose secondary to malposition and was later revised. Clinical outcomes and complications were not statistically significantly different with the numbers available. Conclusion. A substantially different and more extensive initial migration pattern was seen for the GTS stem compared to the Taperloc stem. Although implant stabilization was achieved, excellent long-term survival similar to that of the Taperloc stem should not be inferred. Especially in the absence of clinically proven relevant improvement, widespread usage should be postponed until long-term safety has been established. Cite this article: Bone Joint J 2020;102-B(6):699–708

The increase in revision joint replacement surgery and fractures of bone around orthopaedic implants may be partly addressed by keeping bone healthy around orthopaedic implants by inserting implants with mechanical properties closer to the patient's bone properties. We do not currently have an accurate way of calculating a patient's bone mechanical properties. We are therefore investigating whether microindentation can accurately calculate bone stiffness. We received ethical approval to retrieve femoral heads and necks from patients undergoing hip replacement surgery for research. Cortical bone from the medial calcar region of the femoral neck was cut into 3×3×6mm cuboid specimens. Micro-indentation testing was performed in the direction of loading of the bone using a MicroMaterials indenter. The samples were kept hydrated and were not fixed or polished. From the unloading curve after indentation, the elastic modulus was calculated, using the Oliver- Pharr method. To assess which microindentation machine settings most precisely calculate the elastic modulus we varied the loading and unloading rates, load and indenter tip shape. The most precise results were obtained by using a spherical indenter tip (rather than Berkovich tip), high load (10N), a loading rate of 100 mN/s and unloading rate of 300 mN/s with a pause of 60 seconds at maximum load and multiple load cycles with constant loads. Using these settings the mean elastic modulus over 12 cycles of testing was 13.0 GPa (+/- 2.47). By using a spherical indenter tip and fast unloading it was possible to get precise apparent modulus values. By unloading as fast as possible the effects of bone viscoelastic properties are minimised. By using a spherical indenter tip, plastic deformation at the tip is minimised (compared to the Berkovich tip). We are performing further standard compression tests on the samples to verify the accuracy of the indentation tests

Revision surgeries for orthopaedic infections are done in two stages – one surgery to implant an antibiotic spacer to clear the infection and another to install a permanent implant. A permanent porous implant, that can be loaded with antibiotics and allow for single-stage revision surgery, will benefit patients and save healthcare resources. Gyroid structures can be constructed with high porosity, without stress concentrations that can develop in other period porous structures [1] [2]. The purpose of this research is to compare the resulting bone and prosthesis stress distributions when porous versus solid stems are implanted into three proximal humeri with varying bone densities, using finite element models (FEM). Porous humeral stems were constructed in a gyroid structure at porosities of 60%, 70%, and 80% using computer-aided design (CAD) software. These CAD models were analyzed using FEM (Abaqus) to look at the stress distributions within the proximal humerus and the stem components with loads and boundary conditions representing the arm actively maintained at 120˚ of flexion. The stem was assumed to be made of titanium (Ti6Al4V). Three different bone densities were investigated, representing a healthy, an osteopenic, and an osteoporotic humerus, with an average bone shape created using a statistical shape and density model (SSDM) based on 75 cadaveric shoulders (57 males and 18 females, 73 12 years) [3]. The Young's moduli (E) of the cortical and trabecular bones were defined on an element-by-element basis, with a minimum allowable E of 15 MPa. The Von Mises stress distributions in the bone and the stems were compared between different stem scenarios for each bone density model. A preliminary analysis shows an increase in stress values at the proximal-lateral region of the humerus when using the porous stems compared to the solid stem, which becomes more prominent as bone density decreases. With the exception of a few mesh dependent singularities, all three porous stems show stress distributions below the fatigue strength of Ti-6Al-4V (410 MPa) for this loading scenario when employed in the osteopenic and osteoporotic humeri [4]. The 80% porosity stem had a single strut exceeding the fatigue strength when employed in the healthy bone. The results of this study indicate that the more compliant nature of the porous stem geometries may allow for better load transmission through the proximal humeral bone, better matching the stress distributions of the intact bone and possibly mitigating stress-shielding effects. Importantly, this study also indicates that these porous stems have adequate strength for long-term use, as none were predicted to have catastrophic failure under the physiologically-relevant loads. Although these results are limited to a single boney geometry, it is based on the average shape of 75 shoulders and different bone densities are considered. Future work could leverage the shape model for probabilistic models that could explore the effect of stem porosity across a broader population. The development of these models are instrumental in determining if these structures are a viable solution to combatting orthopaedic implant infections

Abstract. INTRODUCTION. Polyetheretherketone (PEEK) is a high-performance thermoplastic polymer which has found increasing application in orthopaedic implant devices and has a lot of promise for ‘made-to-measure’ implants produced through additive manufacturing [1]. However, a key limitation of PEEK is that it is bioinert and there is a requirement to functionalise its surface to make the material osteoconductive to ensure a more rapid, improved and stable fixation, in vivo. One approach to solving this issue is to modify PEEK with bioactive materials, such as hydroxyapatite (HA). OBJECTIVE. To 3D PEEK/HA composite materials using a Fused Filament Fabrication (FFF) approach to enhance the properties of the PEEK matrix. METHODS. PEEK/HA composites (0–30% w/w HA/PEEK) were 3D printed using a modified Ultimaker 2+ 3D printer. The mechanical, thermal, physical, chemical and in vitro properties of the 3D printed samples were all studied as part of this work. RESULTS. The CT images of both the filament and the 3D printed samples showed that the HA material was evenly dispersed throughout the bulk all the samples. SEM/EDX measurements highlighted that HA was homogenously distributed across the surface. As the HA content of the samples increases, so does the tensile modulus, ranging from 4.2 GPa (PEEK) to 6.1 GPa (30% HA/PEEK) and are significantly higher than datasheet information of injected molded PEEK samples. All materials supported the growth of osteoblast cells on their surface. CONCLUSIONS. The results clearly show that we can successfully and easily 3D print HA/PEEK composite materials up to 30% w/w HA/PEEK. The samples produced have a homogeneous distribution of HA in both the bulk and surface of all the samples, and their mechanical performance of the PEEK is enhanced by the addition of HA

Recent studies have shown that random disorder nanotopography increases osteoblast differentiation and bone formation. This has great potential merit in producing surfaces where osteointegration is required such as spinal fusion surgery and arthroplasty. However, the long-term failure of orthopaedic implants is often related to osteoclast mediated osteolysis and loosening. It is vitally important that we understand the effect of nanotopography on osteoclast formation and bone remodeling. We developed an unique osteoblast/osteoclast co-culture system derived from human mesenchymal and haematopoetic stem cells. This was co-cultured on both nanopatterned and unpatterned polycarbonate substrates. We assessed the co-culture using electron microscopy (SEM), protein expression using immunofluorescence and histochemical staining and gene expression using polymerase chain reaction (PCR). Co-culture of both osteoclasts and osteoblasts was confirmed with mature bone nodules and resorption pits identified on both surfaces. Significantly increased osteoblast differentiation and bone formation was noted on disordered nanotopography. Antagonistic genes controlling osteoclast activity were both upregulated with no significant difference in osteoclast marker gene expression. Our results confirm successful co-culture of osteoblasts and osteoclasts using an unique method closely resembling the in vivo environment encountered by orthopaedic implants. Nanotopography increases osteoblast differentiation and bone formation as previously identified, with possible subsequent increase in osteoclast mediated bone turnover

Open limb fractures are typically due to a high energy trauma. Several recent studied have showed treatment's superiority when a multidisciplinary approach is applied. World Health Organization reports that isolate limb traumas have an incidence rate of 11.5/100.000, causing high costs in terms of hospitalization and patient disability. A lack of experience in soft tissue management in orthopaedics and traumatology seems to be the determining factor in the clinical worsening of complex cases. The therapeutic possibilities offered by microsurgery currently permit simultaneous reconstruction of multiple tissues including vessels and nerves, reducing the rate of amputations, recovery time and preventing postoperative complications. Several scoring systems to assess complex limb traumas exist, among them: NISSSA, MESS, AO and Gustilo Anderson. In 2010, a further scoring system was introduced to focus open fractures of all locations: OTA-OFC. Rather than using a single composite score, the OTA-OFC comprises five components grades (skin, arterial, muscle, bone loss and contamination), each rated from mild to severe. The International Consensus Meeting of 2018 on musculoskeletal infections in orthopaedic surgery identified the OTA-OFC score as an efficient catalogue system with interobserver agreement that is comparable or superior to the Gustilo-Anderson classification. OTA-OFC predicts outcomes such as the need for adjuvant treatments or the likelihood of early amputation. An orthoplastic approach reconstruction must pay adequate attention to bone and soft tissue infections management. Concerning bone management: there is little to no difference in terms of infection rates for Gustilo-Anderson types I–II treated by reamed intramedullary nail, circular external fixator, or unreamed intramedullary nail. In Gustilo-Anderson IIIA-B fractures, circular external fixation appears to provide the lowest infection rates when compared to all other fixation methods. Different technique can be used for the reconstruction of bone and soft tissue defects based on each clinical scenario. Open fracture management with fasciocutaneous or muscle flaps shows comparable outcomes in terms of bone healing, soft tissue coverage, acute infection and chronic osteomyelitis prevention. The type of flap should be tailored based on the type of the defect, bone or soft tissue, location, extension and depth of the defect, size of the osseous gap, fracture type, and orthopaedic implantation. Local flaps should be considered in low energy trauma, when skin and soft tissue is not traumatized. In high energy fractures with bone exposure, muscle flaps may offer a more reliable reconstruction with fewer flap failures and lower reoperation rates. On exposed fractures several studies report precise timing for a proper reconstruction. Hence, timing of soft tissue coverage is a critical for length of in-hospital stay and most of the early postoperative complications and outcomes. Early coverage has been associated with higher union rates and lower complications and infection rates compared to those reconstructed after 5-7 days. Furthermore, early reconstruction improves flap survival and reduces surgical complexity, as microsurgical free flap procedures become more challenging with a delay due to an increased pro-thrombotic environment, tissue edema and the increasingly friable vessels. Only those patients presenting to facilities with an actual dedicated orthoplastic trauma service are likely to receive definitive treatment of a severe open fracture with tissue loss within the established parameters of good practice. We conclude that the surgeon's experience appears to be the decisive element in the orthoplastic approach, although reconstructive algorithms may assist in decisional and planification of surgery

Originally introduced in 1997, porous tantalum is an attractive alternative metal for orthopaedic implants because of its unique mechanical properties. Porous tantalum has been used in numerous types of orthopaedic implants, including acetabular cups in total hip arthroplasty. The early clinical results from porous tantalum acetabular cups have been promising. The purpose of this study was to evaluate the presence of bone ingrowth and the incidence of osteolytic lesions in the acetabular cup -at 10 year follow up – in patients who had a total hip arthroplasty with a monoblock porous tantalum acetabular cup. 50 consecutive patients underwent a total hip arthroplasty with a monoblock porous tantalum acetabular component. All patients had computed tomography at an average of 10 years of follow-up. The computed tomography scan used a standard, validated protocol to evaluate bony ingrowth in the cup and for the presence of osteolysis. The computed tomographic scans showed evidence of extensive bony ingrowth, and no evidence of osteolysis. This study reports the 10-year results of a monoblock porous tantalum acetabular cup. This is the first study to evaluate a porous tantalum acetabular cup with the use of computed tomography. These results show that a porous tantalum monoblock cup has excellent bony ingrowth and no evidence osteolysis at 10 year follow-up. These results suggest that porous tantalum is an attractive material for implantation in young, active patients

The treatment of orthopedic implant infections is often difficult and complex, although the chances of successful treatment with a properly selected diagnostic, surgical and antibiotic treatment protocol have recently increased significantly. Surgical treatment is a key factor in the treatment of infections of orthopedic implants, and any errors in this respect often lead to worse clinical outcomes. Surgical errors. The most important and frequent surgical errors include:. - conservative treatment of periprosthetic infections with antibiotics alone: successful treatment requires adequate surgical procedure combined with long-term antimicrobial Th that is active against biofilm microorganism. Without adequate surgical procedure just the suppression of symptoms is usually achieved, rather than eradication of the infection. - delayed surgical revision: in acute infections, early surgical intervention plays a critical role, especially by patients where retention of the prosthesis is expected. Early evacuation of postop haemathoma after primary or revision surgery is important in order to prevent the possibility of infection. It is important to take into consideration, that a postop apparently superficial surgical site infection may be indicative of deeper infection involoving the implant. - insufficient debridement during surgical revision: thorough and extensive debridement is the most critical predictor of success (removal of the haemathoma, abscess formations, fibrous membranes, sinus tracts, devitalized bone and soft tissue, removal of all cement, cement restrictors, foreign and prosthetic material; eventual exchange of modular components and liners). Finally meticulous irrigation of the op region is obligatory. - inadequate intraoperative sampling for bacteriological and histological analysis: tissue samples from the areas with the most florid inflammatory changes have to be taken and sent for bacteriological and histological examination (3–6 samples). Removed implants or parts of them have to be sent to sonication. Swab cultures have low sensitivity and should be avoided. - the importance of selecting the appropriate surgical strategy for the individual patient cannot be overemphasized: not having, following and treating patients with PJI accordingly to an algorithm that is proven and successful one usually leads to unsuccessful clinical results. We present illustrative cases with each common surcical error combined with proper solution. Treatment of PJI is a demanding procedure, the goal is a long-term pain-free functional joint, that can be achieved by eradication of the infection. For a successful clinical outcome an appropriate diagnostic, surgical and antimicrobial procedure for the individual patient has to be selected

Abstract. Objectives. Additive manufacturing (AM) enables fine control over the architecture of porous lattice structures, and the resulting mechanical performance. Orthopaedic implants may benefit from the tailored stiffness/elastic modulus of these AM biomaterials, as the stiffness can be made to closer match the properties of the replaced trabecular bone. Methods. This study used laser powder bed fusion (PBF) to create stochastic porous lattice structures in stainless steel (SS316L) and titanium alloy (Ti6Al4V), with modifications that aimed to overcome PBF manufacturing limitations of build angles. The structures were tested in uni-axial compression (n = 5) in 10 load orientations relative to the structure, including the three orthogonal axes. Results. The testing verified that no hidden peaks in elastic modulus existed in the stochastic structure. The standard deviation of the 10 elastic modulus values in the final structure decreased from 249 MPa to 101 MPa when made in SS316L and from 95.9 MPa to 52.5 MPa for Ti6Al4V, indicating the structures were more isotropic. Conclusions. These modified stochastic lattices have similar stiffness to cancellous bone and have controllable anisotropy, giving them the potential to be used within implants which match the stiffness of trabecular bone. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

It is well established that cell behaviour is responsive to the surrounding environment. Chemistry, material stiffness and topography allow control of cell adhesion, proliferation, growth and differentiation. Biomimicry is playing a role in the next generation of biomaterials, surface engineering on orthopaedic implants may promote improved skeletal integration. Human osteoblasts were cultured on engineered micro-topographical features with nanoscale depths, similar in scale to an osteoclast resorption pit. Three different micro-topographies were used (in addition to planar controls.) created on a hot moulded polymer. The cells were cultured in basal media on surfaces with 20, 30 and 40 micrometer circular pits, each with a depth of 400 nanometers. The cells were fixed at time points 3 days, 21 days and 28 days to allow assessment of cytoskeletal development, production of protein markers of bone production (osteopontin) and mineral deposition respectively. At each time point greater indicators of cell activity and bone production were evident on the 30 and 40 micrometer structures as compared with the 20 micrometer structures and the planar controls. These positive results include increased focal adhesions, stronger expression of intracellular and extracellular osteopontin and more mature nodules of calcium formation. This in vitro study demonstrates that micro and nanotopographies influence cell activity. Osteoblast response can be induced on the surface of a future generation of orthopaedic implants, lasting long after the effects chemical application have expired. Further research is required to assess the potential application to implant grade materials

Titanium is a popular orthopaedic implant material, but it requires surface modification techniques to improve osseointegration and long term functionality. This project compares a new method of modifying surface topography (nano-patterning) with an existing clinical technology (grit-blasting and acid-etching (GAE)). Titanium discs were blasted with aluminium oxide and etched in sulphuric and acetic acid. Injection moulded discs (with two different nano-patterns) were coated in titanium by evaporation. The topography and chemistry of the discs was assessed using atomic force microscopy (AFM), scanning electron microscopy (SEM), water contact angle measurements, and X-ray photo-electron spectroscopy (XPS). Two discs were plated bilaterally onto a flattened area of the tibiae of 12 rabbits. Tibiae were removed after 4 and 8 weeks for histological assessment of the bone-implant contact (BIC) ratio. AFM and SEM demonstrated a difference in pattern between the square array of nano-pits (SQ) and the randomly positioned nano-pits (RAND). The GAE implants exhibited increased surface roughness (Ra = 570nm) compared to the titanium coated SQ and RAND implants (Ra = 12nm). Water contact angle measurements showed the surface had comparable wettability and XPS demonstrated similar chemical compositions, except GAE surfaces contained 6.8% aluminium. Histological samples analysed at 4 weeks showed a BIC ratio of 36% for GAE, 56% for SQ, and 48% for RAND. At 8 weeks, the BIC ratio was 52% for GAE, 80% for SQ, and 72% for RAND implants. This increase in BIC at 8 weeks for both SQ and RAND implants compared to GAE was statistically significant (P < 0.05). This project demonstrated there was an increase in interfacial bone to implant contact when using a nano-scale topography incorporating nano-pits compared to conventional grit-blasted acid-etched micro-scale topographies. This enhancement of BIC may reduce long term loosening of orthopaedic implants due to mechanical and biological attrition at the interface

Introduction. The increase in revision joint replacement surgery and fractures of bone around orthopaedic implants may be partly addressed by keeping bone healthy around orthopaedic implants by inserting implants with mechanical properties closer to the patient's bone properties. We do not currently have an accurate way of calculating a patient's bone mechanical properties. We therefore posed a simple question: can data derived from a micro-indenter be used to calculate bone stiffness?. Methods. We received ethical approval to retrieve femoral heads and necks from patients undergoing hip replacement surgery for research. Cortical bone from the medial calcar region of the femoral neck was cut into 3×3×6mm cuboid specimens using a diamond wafering blade. Micro-indentation testing was performed in the direction of loading of the bone using a MicroMaterials (MicroMaterials, UK) indenter, using the high load micro-indentation stage (see Figure 1). To simulate in vivo testing, the samples were kept hydrated and were not fixed or polished. From the unloading curve after indentation, the elastic modulus was calculated, using the Oliver-Pharr method using the indentation machine software. To assess which microindentation machine settings most precisely calculate the elastic modulus we varied the loading and unloading rates, load and indenter tip shape (diamond Berkovich tip, 1mm diameter Zirconia spherical tip and 1.5mm diameter ruby spherical tip). Following this, for 11 patients' bone, we performed compression testing of the same samples after they were indented with the 1.5mm diameter ruby spherical tip to assess if there was a correlation between indentation values of apparent elastic modulus and apparent modulus values calculated by compression testing (see Figure 2). Platens compression testing was performed using an Instron 5565 (Instron, USA) materials testing machine. Bluehill compliance correction software (Instron, USA) was used to correct for machine compliance. The strain rate was set at 0.03mm/s. The apparent elastic modulus was calculated from the slope of the elastic region of the stress-strain graph. The correlation between values of apparent modulus from compression testing and indentation were analyzed using IBM SPSS Statistics 22. Results. The most precise results were obtained using a spherical indenter tip (1.5 mm diameter ruby ball), rather than a sharp Berkovich tip, high load (10N), a loading rate of 100 mN/s and unloading rate of 300 mN/s with a pause of 60 seconds at maximum load. We also used multiple load cycles with a peak load of 10N (see Figure 3). Using these optimal settings we calculated the mean elastic modulus over 10 cycles of testing with six indents on one sample to be 11.8 GPa (+/− 1.01). There was a moderate correlation between indentation and compression values of apparent modulus (r=0.62, n=11, p=0.04). Discussion. By using a spherical indenter tip and fast unloading it was possible to get precise apparent modulus values. The apparent modulus derived from micro-indentation, correlated moderately with that derived from direct compression testing. This early data suggests that microindentation may become a clinically relevant test of bone quality in real time

Objectives. Prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasty. Non-contact induction heating of metal implants is a new and emerging treatment for PJI. However, there may be concerns for potential tissue necrosis. It is thought that segmental induction heating can be used to control the thermal dose and to limit collateral thermal injury to the bone and surrounding tissues. The purpose of this study was to determine the thermal dose, for commonly used metal implants in orthopaedic surgery, at various distances from the heating centre (HC). Methods. Commonly used metal orthopaedic implants (hip stem, intramedullary nail, and locking compression plate (LCP)) were heated segmentally using an induction heater. The thermal dose was expressed in cumulative equivalent minutes at 43°C (CEM43) and measured with a thermal camera at several different distances from the HC. A value of 16 CEM43 was used as the threshold for thermal damage in bone. Results. Despite high thermal doses at the HC (7161 CEM43 to 66 640 CEM43), the thermal dose at various distances from the HC was lower than 16 CEM43 for the hip stem and nail. For the fracture plate without corresponding metal screws, doses higher than 16 CEM43 were measured up to 5 mm from the HC. Conclusion. Segmental induction heating concentrates the thermal dose at the targeted metal implant areas and minimizes collateral thermal injury by using the non-heated metal as a heat sink. Implant type and geometry are important factors to consider, as they influence dissipation of heat and associated collateral thermal injury. Cite this article: B. G. Pijls, I. M. J. G. Sanders, E. J. Kuijper, R. G. H. H. Nelissen. Segmental induction heating of orthopaedic metal implants. Bone Joint Res 2018;7:609–619. DOI: 10.1302/2046-3758.711.BJR-2018-0080.R1

Intermittent treatment with parathyroid hormone (PTH) has an anabolic effect on both intact cancellous and cortical bone. Very little is known about the effect of the administration of PTH on the healing of fractures or the incorporation of orthopaedic implants. We have investigated the spontaneous ingrowth of callus and the formation of bone in a titanium chamber implanted at the medioproximal aspect of the tibial metaphysis of the rat. Four groups of ten male rats weighing approximately 350 g were injected with human PTH (1-34) in a dosage of 0, 15, 60 or 240 μg/kg/day, respectively, for 42 days from the day of implantation of the chamber. During the observation period the chamber became only partly filled with callus and bone and no difference in ingrowth distance into the chamber was found between the groups. The cancellous density was increased by 90%, 132% and 173% in the groups given PTH in a dosage of 15, 60 or 240 μg/kg/day, respectively. There was a linear correlation between bone density and the log PTH doses (r. 2. = 0.6). Our findings suggest that treatment with PTH may have a potential for enhancement of the incorporation of orthopaedic implants as well as a beneficial effect on the healing of fractures when it is given in low dosages

Summary Statement. We are taking very expensive cutting edge technology, usually reserved for industry, and using it with the help of open source free software and a cloud 3D printing services to produce custom and anatomically unique patient individual implants for only £32. This is approx. 1/100. th. of the traditional cost of implant production. Introduction. 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. Our aim was to use freely available open source software, a personal computer and consumer access online cloud 3D printing services to produce an accurate patient specific orthopaedic implant without utilising specialist expertise, capital expenditure on specialist equipment or the involvement of traditional implant manufacturing companies. This was all to be done quickly, cost effectively and in department. Methods & Materials. Using standard computed tomography (CT) scan and the standard file format of digital imaging and communications in medicine (DICOM) data, a 3D surface reconstruction was made of a cadaveric radial head using the software OsiriX (DICOM image processing software for Apple OS X). This data was then processed in Meshlabs (a system for the processing and editing of unstructured 3D triangular meshes) to create a mirror image 3D model of the radial head with a stem added to produce prosthesis suitable to replace the contra lateral radial head. Both packages are distributed under open-source licensing—Lesser General Public Licence (LGPL)—and are therefore free. This was then uploaded and 3D printed using a process of selective laser sintering (SLS) in stainless steel via the commercial cloud printing service . Shapeways.com. . Results & Conclusions. The model produced was an accurate mirror image replica of the patient's original anatomy (all measurements equal +/− 0.2mm using TS411212 Digital Vernier Expert Caliper 300mm P=0.001 Showing no significant statistical difference. Production from original CT scan took a total of 10 days and the total cost including shipping was £32. This was then re-implanted in to the contra lateral cadaveric radius. We achieved our aims and goals of quick, cost effective and accurate implant creation

Background: The clinical significance of bone turnover markers is well recognized, at least in several diseases affecting the bone metabolism. However, their clinical significance (if any) remains still unknown in patients undergoing Total Joint Arthroplasty (TJA). Changes in the levels of some markers have been reported in the early postoperative period after Total Hip Arthroplasty; however their exact postoperative course has not been clearly documented yet. In order to assess the clinical value of biochemical markers when trying to determine the fixation of orthopaedic implants, it is necessary to clarify their normal postoperative course. The aim of this study was to extend the evaluation of the course of bone turnover markers over a longer period (12 postoperative months) following a TJA, and to assess the postoperative course for two of them (RANKL and Osteoprotegerin) for the first time. Methods: The serum levels of RANKL, Osteocalcin, Osteoprotegerin and bALP were determined one day preoperatively and several times during the first postoperative year in patients suffering from idiopathic osteoarthritis that underwent total knee (n=23) and hip arthroplasties (n=24). Results: There were statistically significant changes in the serum levels of all markers over time (p< 0,001). RANKL values initially increased and then gradually decreased. Following an initial decrease, Osteocalcin values continuously increased until the 2nd postoperative month and then continuously decreased. Osteoprotegerin initially increased, then decreased until the 4th postoperative month and then increased again reaching a peak 8 months postoperatively. Bone-specific ALP decreased until the 7th postoperative day. After that time it continuously increased, reaching a peak at the 8th month, and then it gradually decreased. There were no major differences in the postoperative course of all markers between the hip and knee arthroplasties. Conclusions: The levels of all bone markers did not uniformly ‘return’ to their preoperative values one year postoperatively. A one-year period is not enough, when assessing an orthopaedic implant’s fixation with the use of bone turnover markers

Aims. Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment. Methods. The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load. Results. PlySs2 treatment reduced 99% more CFUs and 75% more biofilm compared with vancomycin in vitro. A combination of PlySs2 and vancomycin in vivo reduced the number of CFUs on the surface of implants by 92% and in the periprosthetic tissue by 88%. Conclusion. PlySs2 lysin was able to reduce biofilm, target planktonic bacteria, and work synergistically with vancomycin in our in vitro models. A combination of PlySs2 and vancomycin also reduced bacterial load in periprosthetic tissue and on the surface of implants in a murine model of DAIR treatment for established PJI. Cite this article: Bone Joint J 2020;102-B(7 Supple B):3–10

Introduction & Aims. In other medical fields, smart implantable devices are enabling decentralised monitoring of patients and early detection of disease. Despite research-focused smart orthopaedic implants dating back to the 1980s, such implants have not been adopted into regular clinical practice. The hardware footprint and commercial cost of components for sensing, powering, processing, and communicating are too large for mass-market use. However, a low-cost, minimal-modification solution that could detect loosening and infection would have considerable benefits for both patients and healthcare providers. This proof-of-concept study aimed to determine if loosening/infection data could be monitored with only two components inside an implant: a single-element sensor and simple communication element. Methods. The sensor and coil were embedded onto a representative cemented total knee replacement. The implant was then cemented onto synthetic bone using polymethylmethacrylate (PMMA). Wireless measurements for loosening and infection were then made across different thicknesses of porcine tissue to characterise the sensor's accuracy for a range of implantation depths. Loosening was simulated by taking measurements before and after compromising the implant-cement interface, with fluid influx simulated with phosphate-buffered saline solution. Elevated temperature was used as a proxy for infection, with the sensor calibrated wirelessly through 5 mm of porcine tissue across a temperature range of 26–40°C. Results. Measurements for loosening and infection could be acquired simultaneously with a duration of 4 s per measurement. For loosening, the debonded implant-cement interface was detectable up to 10 mm with 95% confidence. For temperature, the sensor was calibrated with a root mean square error of 0.19°C at 5 mm implantation depth and prediction intervals of ±0.38°C for new measurements with 95% confidence. Conclusions. This study has demonstrated that with only two onboard electrical components, it is possible to wirelessly measure cement debonding and elevated temperature on a smart implant. With further development, this minimal hardware/cost approach could enable mass-market smart arthroplasty implants

Joint replacement of the hip and knee remain very satisfactory operations. They are, however, expensive. The actual manufacturing of the implant represents only 30% of the final cost, while sales and marketing represent 40%. Recently, the patents on many well established and successful implants have expired. Companies have started producing and distributing implants that purport to replicate existing implants with good long-term results. The aims of this paper are to assess the legality, the monitoring and cost saving implications of such generic implants. We also assess how this might affect the traditional orthopaedic implant companies. Cite this article: Bone Joint J 2016;98-B:892–900

Background: The success of the increasing number of arthroplasty, spinal instrumentation and other implanted orthopaedic devices is hampered by device-related infections. More than half of these infections are caused by staphylococcal biofilm mediated antibiotic resistance. The hope of preventing prosthetic joint infection by antibiotic loaded cement is threatened by emerging resistant organisms. No bacterial resistance to betadine has been reported. Current intervention strategy is focussed on prevention of initial device colonisation and inhibition of genes encoding biofilm formation. Aim:. Determine the minimum inhibitory concentration (MIC) of betadine. Investigate the effect of betadine on icaADBC operon encoded staphylococcal biofilm formation. Investigate wether betadine can prevent bacterial adherence and biofilm formation by inhibition of the encoding genes. Methods: MIC of betadine for both reference strains and strains isolated from infected orthopaedic implants was determined. Biofilm assay was performed at different betadine concentrations using 96-well polystyrene plates. Total RNA for cDNA synthesis was isolated from bacterial at different twofold dilutions of betadine concentrations. Real time polymerase chain reaction was used to quantify effects of betadine on gene expression pattern of the icaADBC operon using the constitutively expressed gyrB gene as internal control. Bacterial was cultivated on polystyrene plates coated with different sub-inhibitory and clinical in-use doses of betadine to assess surface adherence. Results: The MIC of betadine was 1.4% for all bacterial strains. Clinical in-use doses of betadine prevented biofilm formation. A step-wise reduction of biofilm was observed at increasing sub-inhibitory doses of betadine (p< 0.0001). IcaA expression correlated with biofilm formation in staphylococcal organisms. Decrease in icaA expression was strongly associated with an increase in expression in the biofilm repressor gene, icaR. The repressive effect of betadine on biofilm formation by Staphylococcal bacteria is by a separate mechanism from its bacteriostatic mechanism of action. Conclusion: This study shows that icaR is a potential therapeutic target through which the ability of Staphylococcal bacterial to form biofilm may be reduced. Sub-inhibitory dose of betadine inhibited biofilm formation. Prevention of bacterial surface attachment as demonstrated by this study is suggestive that these compounds could be developed as a surface coating agents for orthopaedic implants

Objective. Superior bone ingrowth and resistance to bacterial infection are ideal for orthopaedic implants. We compared new bone formation, strength of bone bonding, and infection rates between silicon nitride ceramic (Si3N4; abbreviated SiN), medical-grade PEEK (PEEK), and titanium (Ti) in rat calvariae. PEEK and Ti are used in spinal and arthroplasty implants respectively, while SiN is a non-oxide ceramic used in spinal implants for the past 4 years. Methods. Specimens of 10 mm × 10 mm by 1.75 mm size were implanted into experimental calvarial defects in 2-year old Wistar rats using standard surgical techniques (n's: SiN=48; PEEK=24; Ti=24). One group of animals was immediately inoculated with 1 × 104 Staphylococcus epidermidis; control animals received saline only. After sacrifice at 3 days, 7 days, 14 days, and 3 months post-inoculation (n=4 rats per time period), one calvarial sample each for PEEK and Ti, and two samples for SiN (per bacterial condition and time point) were retrieved for histology; remaining samples were used for sample push-out testing with a Micro Tester 5848 (Instron) with a 1-kN load cell, using published techniques. New bone formation was measured with tetracycline double-labeling at 11 and 4 days before the 14-day and 3-month time periods. Results. Of the materials tested, 3-month bone ingrowth and periprosthetic infection rates were most favorable for SiN (Fig. 1). At 90 days post-implantation without bacteria, new bone growth in calvariae with SiN was ∼69% compared with 24% and 36% for PEEK and Ti, respectively. With bacterial inoculation, new bone growth was 21%, 26% and 41% for PEEK, Ti, and SiN, respectively. At 3-months, live bacteria were observed for PEEK (88%) and Ti (21%), while no bacteria were present around SiN (Fig. 2). Push-out strength was greater for SiN when compared to Ti and PEEK (Fig. 3). Conclusions. Superior bone formation, bone ingrowth, and bacterial resistance were associated with SiN when compared to Ti and PEEK. SiN proved effective in inhibiting bacteria and promoting osteogenesis in experimental osseous defects, when compared to Ti and PEEK. These observations are most likely related to the hydrophilic properties of SiN that contributed to the adsorption of proteins known to decrease bacteria attachment and growth (vitronectin and fibronectin). We conclude that SiN may be a superior biomaterial for the development of orthopaedic implants

Introduction and Objective. The choice of appropriate characteristics is crucial to favor a firm bonding between orthopedic implants and the host bone and to permit bone regeneration. In particular, the morphology and composition of the biointerface plays a crucial role in orchestrating precise cellular responses. Here, to modulate the biointerface, we propose new biomimetic coatings, having multi-scale nano- to micro- morphological cues and a composition mimicking the mineral phase of bone. Materials and Methods. Films on various substrates are obtained by Ionized Jet Deposition (IJD), by ablation of biogenic apatite and annealing at 400°C for 1 hour. Films are proposed for functionalization of metallic implants, but application to heat sensitive porous (3D printed) substrates is also shown, as it permits to further boost biomimicry (by addition of collagen/gelatin), thus reproducing the architecture of cancellous bone. In IJD, coatings thickness can be selected by tuning deposition duration. Here, a 450 nm thickness is selected based on preliminary results. Micro-rough titanium alloy (Ti6Al4V) disks (roughness 5 μm) are used as a substrate for the deposition and as a control. The coatings are characterized in terms of composition (GI-XRD, EDS, FT-IR microscopy), morphology (FEG-SEM, AFM, data processing by ImageJ), mechanical properties (micro-scratch test) and dissolution profile in medium (pH 7.4, FEG-SEM). Then, their behavior is characterized in vitro (human bone marrow-derived mesenchymal stromal cells - hMSCs), by studying cells early adhesion (focal adhesion by vinculin staining), viability (Alamar Blue), morphology (SEM) and differentiation (expression of RUNX2, ALPL, SPARC and COL1A1, BMP2, BGLAP, osteocalcin, alkaline phosphatase, collagen type I) at 3, 7 and 14 days. Results. Films exhibit a biomimetic composition, as they are constituted by a nanocrystalline multi-doped carbonated hydroxyapatite. EDS indicates the presence of trace ions sodium (0,11 ± 0,02 wt%) and magnesium (0,47 ± 0,05 wt%), uniformly distributed in the coating in a percentage close to native bone. These ion-substitutions are crucial, as each ion modifies apatite solubility and ion-release in the peri-implant environment and has important biological role. Films have a high adhesion to the substrates and a suitable dissolution profile. The morphology is highly rough, as films are composed by nanosized grains (minimum diameter 40 nm) aggregated in multi-scale clusters (diameter range: 100 nm-2 μm). Morphology of the aggregates can be tuned by selecting deposition duration and also depends on the morphology, roughness and composition of the substrate. Because of the nanoscale thickness of the films, they do not alter the microscale features of the implants. For fibrous substrates, films grow onto the fibers surface, with no pore occlusion or damage to substrate composition. Coatings do not alter the metabolic activity of MSCs but influence their early adhesion, morphology and differentiation. More in detail, MSCs on coated disks show a branched shape, while those on the controls show a more spindle and elongated morphology. Coatings increase hMSCs early adhesion, as a higher density and a greater area of focal adhesions are observed at 24 hours. Finally, they can trigger a signaling pathway that promotes the osteogenic differentiation of hMSCs, as confirmed by quantification of osteocalcin, alkaline phosphatase and collagen, even in the absence of osteogenesis-inducing factors. Conclusions. The topographical and chemical cues of the biomimetic nanostructured coating are perceived by hMCSs, showing that combining morphological and biomimetic cues is a promising route for the development of cells-instructive biomaterials for orthopedics. In vivo tests on rabbit models are in progress

Calcium phosphates-based coatings have been widely studied to favour a firm bonding between orthopaedic implants and the host bone. To this aim, thin films (thickness below 1 μm) having high adhesion to the substrate and a nanostructured surface texture are desired, capable of boosting platelet, proteins and cells adhesion. In addition, a tunable composition is required to resemble as closely as possible the composition of mineralized tissues and/or to intentionally substitute ions having possible therapeutic functions. The authors demonstrated nanostructured films having high surface roughness and a composition perfectly resembling the deposition target one can be achieved by Ionized Jet Deposition (IJD). Highly adhesive nanostructured coatings were obtained by depositing bone-apatite like thin films by ablation of deproteinized bovine bone, capable of promoting host cells attachment, proliferation and differentiation. Here, biomimetic films are deposited by IJD, using biogenic and synthetic apatite targets. Since IJD deposition can be carried out without heating the substrate, application on heat sensitive polymeric substrate, i.e. 3D printed porous scaffolds, is investigated. Biogenic apatite coatings are obtained by deposition of deproteinized bone (bovine, ovine, equine, porcine) and compared to ones of stoichiometry hydroxyapatite (HAp). Coatings composition (FT-IR-ATR, FT-IR microscopy, XRD, EDS) and morphology (SEM, AFM) are tested for deposition onto metallic and 3D-printed polymeric substrates (polyurethane (PU)). Different post-treatment annealing procedures for metallic substrates are compared (350–425°C), to optimize crystallinity. Then, uniformity of substrate coverage and possible damage caused to the polymeric substrate are studied by SEM, DSC and FT-IR microscopy. Biogenic coatings are composed by carbonated HAp (XRD, FT-IR). Trace ions Na. +. and Mg. 2+. are transferred from deposition target to coating. All coatings are nanostructured, composed by nano-sized globular aggregates, of which morphology and dimensions depend on the target characteristics. As-deposited coatings are amorphous, but crystallinity can be tuned by post-treatment annealing. A bone-like crystallinity can be achieved for heating at ≥400°C, also depending on duration. When deposited on 3D-printed PU scaffolds, coatings, owing to sub-micrometric thickness, coat them entirely, without altering their fibre shape and porosity. Obtained biomimetic bone apatite coatings can be deposited onto a variety of metallic and polymeric biomedical devices, thus finding several perspective applications in biomedical field

Bioabsorbable metals hold a lot of potential as orthopaedic implant materials. Three metal families are currently being investigated: iron (Fe), magnesium (Mg) and zinc (Zn). Currently, however, biodegradation of such implants is poorly predictable. We thus used Direct Metal Printing to additively manufacture porous implants of a standardized bone-mimetic design and evaluated their mechanical properties and degradation behaviour, respectively, under in vivo-like conditions. Atomized powder was manufactured to porous implants of repetitive diamond unit cells, using a ProX DMP 320 (Layerwise, Belgium) or a custom-modified ReaLizer SLM50 metal printer. Degradation behaviour was characterized under static and dynamic conditions in a custom-built bioreactor system (37ºC, 5% CO. 2. and 20% O. 2. ) for up of 28 days. Implants were characterized by micro-CT before and after in vivo-like degradation. Mechanical characterization (according to ISO 13314: 2011) was performed on an Instron machine (10kN load cell) at different immersion times in simulated body fluid (r-SBF). Morphology and composition of degradation products were analysed (SEM, JSM-IT100, JEOL). Topographically identical titanium (Ti-6Al-4V, Ti64) specimen served as reference. Micro-CT analyses confirmed average strut sizes (420 ± 4 μm), and porosity (64%), to be close to design values. After 28 days of in vivo-like degradation, scaffolds were macroscopically covered by degradation products in an alloy-specific manner. Weight loss after cleaning also varied alloy-specifically, as did the change in pH value of the r-SBF. Corrosion time-dependent changes in Young's moduli from 1200 to 800 MPa for Mg, 1000 to 700 MPa for Zn and 48-8 MPa for iron were statistically significant. In summary, DMP allows to accurately control interconnectivity and topology of implants from all three families and micro-structured design holds potential to optimize their degradation speed. This first systematic report sheds light into how design influences degradation behaviour under in vivo-like conditions to help developing new standards for future medical device evaluation

Summary Statement. In vivo microCT allows monitoring of subtle bone structure changes around infected implants in a rat model. Introduction. The principal causes of orthopedic implant revisions are periprosthetic bone loss and infections. Immediately after implantation, a dynamic process of bone formation and resorption takes place around an orthopedic implant, influencing its mechanical fixation. Despite its importance, the effect of bacteria on the temporal pattern of periprosthetic remodeling is still unknown. The aim of this study was to evaluate the morphological changes of bone adjacent to an implant in the presence and absence of infection using micro computed tomography (microCT). Materials and methods. Twenty-four three-month-old female Wistar rats were used in this study. Twelve rats received a single control screw (sterile) in the proximal part of the right tibia while the other twelve received an infected screw (1×10. 4. CFU Staphylococcus aureus). The self-tapping cancellous bone screws, custom made of PEEK and coated with 30µm of titanium, were 2mm in outer diameter and 5mm in length. Bone changes around the screws were assessed using in vivo microCT with a nominal isotropic resolution of 12mm (at 70 kV, 300 ms integration time, 1000 projections) at days 0, 3, 6, 9, 14, 20 and 27. Each measurement took approximately 30 min while the animal was anesthetised via isoflurane inhalation. After reconstruction, these data were registered in space. The screw was segmented and dilated to define a region surrounding the coating. Bone-implant contact (BIC) was defined as the bone volume fraction (BV/TV) within this region. The changes in bone structure were computed from the differences between two consecutive time points. After sacrifice, in each group six tibiae were prepared for histology and six were used for mechanical pullout of the screw from the tibia, then quantitative microbiological analysis was carried-out after homogenization of the bone sample and sonication of the screw. Results. In the control group, no animal showed an infection, while all animals in the infected group developed an infection. In the uninfected group, BIC increased from 35±5% to 55±10% between day 0 and day 27 (p<0.05); at day 27 pullout stiffness was 220±48 N/mm and the maximal force 120±16 N. The microstructural changes were most prominent between day 0 and day 14. In the infected group, BIC dramatically dropped to zero within 14 days and the animals were sacrificed. Histology revealed that in the infected group there was marked osteolysis, purulent inflammation and a fibrous capsule around the screws. The pullout stiffness and maximal force were not significant (respectively 39±54 N/mm and 12±16 N). While 1×10. 4. CFU were introduced at day 0, at day 27, microbiological analysis revealed 1×10. 6. CFU on the screws and 5×10. 5. CFU in the neighboring bone. Conclusion. High-resolution in vivo microCT shows in the current model a rapid progression of osteolysis. This new approach allows a better understanding of the changes in bone structure around S. aureus infected implants. It may be particularly useful in detecting low-grade infections, such as S. epidermidis infections in the same model

Problem. The identification of unknown orthopaedic implants is a crucial step in the pre-operative planning for revision joint arthroplasty. Compatibility of implant components and instrumentation for implant removal is specific based on the manufacturer and model of the implant. The inability to identify an implant correctly can lead to increased case complexity, procedure time, procedure cost and bone loss for the patient. The number of revision joint arthroplasty cases worldwide and the number implants available on the market are growing rapidly, leading to greater difficulty in identifying unknown implants. Solution. The solution is a machine-learning based mobile platform which allows for instant identification of the manufacturer and model of any implant based only on the x-ray image. As more surgeons and implant representatives use the platform, the model should continue to improve in accuracy and number of implants recognized until the algorithm reaches its theoretical maximum of 99% accuracy. Market. Multiple organizations have created small libraries of implant images to assist surgeons with manual identification of unknown implants based on the x-ray, however no automated implant identification system exists to date. One of the most financially successful implant identification tools on the market is a textbook of hip implants which sells for a per unit cost of $200. Several free web-based resources also act as libraries for the manual identification of a limited number of arthroplasty implants. A number of academic and private organizations are working on the development of an automated system for implant identification, however none are available to the public. Product. Implant Identifier is mobile application which uses machine-learning to instantly detect the model and manufacturer of any common arthroplasty implant, based only on x-ray. The beta version offers a large library of implants for manual identification and is currently available for free download on iOS and Android. Its purpose is to further develop the model to its maximal theoretical accuracy, prior to official release. The beta version of the application currently has over 15,000 registered users worldwide and has the largest publicly available arthroplasty library available on the market. Over 200,000 implant images have been submitted by users to date. Timescales. The product was initially released in the form of a closed beta which became available to invited guests around 18 months ago. The current version is an open beta which can be downloaded and used by any individual. It was released roughly 12 months ago. The final rendition of the application will allow for free manual identification using the implant library, as well as subscription-based automated implant identification. The implementation, testing and release of this final subscription product is projected to be completed by Q3 2022. Funding. A small number of early investors have funded the initial research and development of the beta product; however, another round of investment will be beneficial in the final evolution of the product. This additional investment round will allow for completion of development of the identification algorithm, product dissemination, customer support, and lasting sustainability of the venture

Taper locking connection has been widely used in orthopedic implant devices. The long term successful clinical results indicated it is a safe and effective structural component. The common materials used are solid titanium and cobalt chromium alloys. Recently, foam metal materials showed promising results of bony in-growth characteristics and became the excellent choices for the orthopedic implants. Clinically it is desirable to taper lock the foam metal component to other structural components. To date there is no data for the foam metal being used directly in taper connection. The purpose of this study was to investigate the static locking strength of the taper junctions made of titanium foam metal comparing to that of conventional solid titanium material. (5) 43mm long and 4mm thick sleeve were machined internally with 17mm major diameter and 3° included taper angle for each 70% porosity CP titanium foam metal and solid Ti6AL4VELI alloy materials. (10) Solid Ti6AL4VELI alloy stems were machined with OD geometry matching the ID of the sleeves. All components were inspected, cleaned and assembled to (5) pairs of each sleeve material combinations with 2224N axial compression force. Each assembled specimen was mounted on MTS Bionix test machine for torque resistance test. The angular displacement at 0.1 degree/sec was applied to the stem when sleeve was rotationally locked. The maximum torque resistance was recorded. The specimen was then re-assembled with 2224N axial compression force. Axial push out test was performed by loading at smaller end of the stem when the opposite end of sleeve was supported. The maximum push out force was recorded. Procedures were repeated for all foam metal and solid metal specimens. The taper interface surfaces were visually inspected to compare two types of sleeve materials. The average torque resistance for foam metal and solid tapers were 20.4Nm (SD=3.68) and 21.7Nm (SD=3.72) respectively (p=0.59). The average axial locking forces were 2035.7N (SD=201.11) for foam metal taper and 1989.3N (SD= 451.84) for solid taper (p=0.839). There was no visual difference observed for tested stem outer and sleeve inner surfaces of foam metal and solid metal pairs. This study suggested that the foam metal sleeve is capable to have comparable taper locking strength as the conventional solid taper components under dry static condition. The study indicated that the contact area does not significantly influence the friction locking. This is in agreement with the friction force definition which depends only on the coefficient of friction and normal contact force

Background: The presence of bacteria forming biofilms or prior antimicrobial use has been shown to reduce the sensitivity of the standard technique (PT cultures) in patients with infection of orthopedic implants. Culturing fluid resulting from sonication (FRS) of prosthesis could improve the microbiologic diagnosis. Objective: To analyze the diagnostic validity of culturing FRS of different orthopedic implants and PT culture. Methods: Between Jan 2007 and Apr 2008, patients undergoing knee or hip prosthesis removal, and those with ostheosyntesis or spinal instrumentation removal, were prospectively included (44 hip prosthesis, 63 knee prosthesis, 91 osteosynthesis and 14 spinal instrumentations). 5 PT specimens were collected for culture. Removed implants were sonicated during 5 min. (40Hz). Both, PT and FRS, were inoculated in aerobic agar (Chocolate Polyvitex), anaerobic agar (Schaedler + 5% blood) and in thioglycolat, for 7 days. Positive culture cut-off was defined as growing of > 5 CFU. Clinical diagnosis of prosthetic-joint infection was made as commonly accepted. Previous antimicrobial therapy was assessed. Diagnostic validity was calculated for both culturing methods. Sensitivity of methods was compared by Chi-square test (SPSS 15.0). Results: 212 cases were included. Diagnostic of infection was made in 17 hip prosthesis (THA), 20 knee prosthesis (TKA), 24 osteosynthesis (OS) and 6 spinal fusions (SI). Tissue culture was positive in 9 THA, 11 TKA 18 OS and 4 SI. Sonication culture was positive in 14 THA, 18TKA, 23 Os and 6 SI. Tissue culture: Sensibility: THA53%, TKA 55%, OS 75% and SI 66%. Specificity: THA 96%, TKA 100%, OS 96%, SI 100%. Sonications: Sensibility: THA 82%, TKA 90%, OS 95% and SI 100%. Specificity: THA 96%, TKA 100%, OS 92%, SI 100%. Statistical differences favoring sonication were found in sensitivity in knee arthroplasty and osteosynthesis implants. 6 patients received antibiotics for > 7 days before implant was removed. Sonication culture was positive in 4 of them whereas only one standard culture yielded positive. Conclusions: FRS cultures are more sensitive than PT cultures. Sensitivity of the method depends on which device is evaluated. Sonication also improves sensitivity of culture after preoperative antimicrobial therapy

Aims. It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. Materials and Methods. An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium. RNA sequencing analysis was performed using sorted CD31. hi. EMCN. hi. endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. Results. Flow cytometry revealed that anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. Conclusion. VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31. hi. EMCN. hi. endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108–114

Direct metal printed (DMP) porous iron implants possess promising mechanical and corrosion properties for various clinical application. Nevertheless, there is a requirement for better co-relation between in vitro and in vivo corrosion and biocompatibility behaviour of such biomaterials. Our present study evaluates absorption of porous iron implants under both static and dynamic conditions. Furthermore, this study characterizes their cytocompatibility using fibroblastic, osteogenic, endothelial and macrophagic cell types. In vitro degradation was performed statically and dynamically in a custom-built set-up placed under cell culture conditions (37 °C, 5% CO2 and 20% O2) for 28 days. The morphology and composition of the degradation products were analysed by scanning electron microscopy (SEM, JSM-IT100, JEOL). Iron implants before and after immersion were imaged by μCT (Quantum FX, Perkin Elmer, USA). Biocompatibility was also evaluated under static and dynamic in vitro culture conditions using L929, MG-63, HUVEC and RAW 264.7 cell lines. According to ISO 10993, cytocompatibility was evaluated directly using live/dead staining (Live and Dead Cell Assay kit, Abcam) in dual channel fluorescent optical imaging (FOI) and additionally quantified by flow cytometry. Furthermore, cytotoxicity was indirectly quantified using ISO conform extracts in proliferation assays. Strut size of DMP porous iron implants was 420 microns, with a porosity of 64% ± 0.2% as measured by micro-CT. After 28 days of physiological degradation in vitro, dynamically tested samples were covered with brownish degradation products. They revealed a 5.7- fold higher weight loss than statically tested samples, without significant changes in medium pH. Mechanical properties (E = 1600–1800 MPa) of these additively manufactured implants were still within the range of the values reported for trabecular bone, even after 28 days of biodegradation. Less than 25% cytotoxicity at 85% of the investigated time points was measured with L929 cells, while MG-63 and HUVEC cells showed 75% and 60% viability, respectively, after 24 h, with a decreasing trend with longer incubations. Cytotoxicity was analysed by two-way ANOVA and post-hoc Tukey's multiple comparisons test. Under dynamic culture conditions, live-dead staining and flow cytometric quantification showed a 2.8-fold and 5.7-fold increase in L929 and MG-63 cell survival rates, respectively, as compared to static conditions. Therefore, rationally designed and properly coated iron-based implants hold potential as a new generation of absorbable Orthopaedic implants

Surgical site infection related to orthopaedic implants is one of the serious complications. In the previous works, we developed a novel thermal spraying technology combined silver with hydroxyapatite (HA) in order to resolve such problems, and reported the property and antibacterial effect of them in vitro. However, no previous reports have investigated in vivo. Therefore, we monitored serum silver level in rats to clarify in vivo kinetics of silver released from the coating. HA loaded with 3 wt % of silver oxide (HA-Ag) and plain HA powder were sprayed on surface of titanium disks (20 mm diameter × 1 mm thick) by the flame spraying, which is a kind of thermal spraying method with acetylene torch. All these test pieces were obtained from Japan Medical Materials Corporation (JMM, Osaka, Japan). Both samples were implanted singly into the back subcutaneous pockets of male Sprague-Dawley rats (150–200 g). Rats were housed individually and given ad libitum access to food and water. After 24 h, 48 h, 7 d, 14 d and 28 d, the rats were sacrificed, and then the blood was drawn from common iliac vein. All procedures were operated under anesthesia. These blood samples were spun down and serum silver levels were measured by an inductively coupled plasma mass spectrometry. The average serum silver level in HA-Ag group had increased to more than 40 ppb until 48 h after implantation, and then decreased rapidly to normal level. There were significant differences (p < 0.05) between HA-Ag and HA group, at each measurement period. This is the first report to elucidate the serum silver level in rats implanted HA-Ag coatings. To date, reported coating technologies have included direct-loading antibacterial agents or heavy metals including silver with prosthesis base. The combine technology HA with silver would be effective in not only antibacterial but also osteoconductive respect. Our experimental results highlight the following 2 features: the serum silver levels peaked relatively early, and the levels reduced immediately to normal level after the peak. Therefore, we speculate that the released silver would not be accumulated generally, which not contribute long-term toxicity, and the coating would be suitable for prevention of early surgical site infections. This study provides novel and important information on in vivo release- property for HA-Ag coating, and suggests this coating is effective against not late but rather early infection related to orthopaedic implants

Bacterial infections related to orthopaedic implants is one of the serious types of complications. Recently, there has been a greater interest in antibacterial biomaterials. However, antibacterial evaluations of each material are inconsistant, so intercomparison of the antibacterial performance is difficult. This study focused on the Japanese Industrial Standards test (JIS Z2801), which is used for antibacterial evaluation of commodities. The study investigated a suitable evaluation method for in vitro antibacterial activity of biamaterials. In 2007, JIS Z2801 test was approved as international standard ISO 22196. Hydroxyapatite (HA) powder containing 3 wt % of silver oxide (Ag) was sprayed on the surface of titanium disks with the thermal spraying method, using an acetylene torch. This coating has been proved to generate strong antibacterial activity in previous studies. The antibacterial activity was examined with the JIS Z 2801 test and modified JIS Z2801 test. The bacterial strains used in JIS Z2801 test were Escherichia coli (E.coli), Staphylococcus aureus (S.aureus). Bacterial culture medium was instilled onto the surface of the test disks (about 106 cells/ml) and covered with polystyrene films. After cultivation in 1/500 Nutrient Broth for 24 h at 35°C, the bacteria was washed out with the broth. The numbers of viable bacteria in the broth were counted with the agar plate culture method. Additionally, Modified JIS Z2801 test was performed. Modified points were added to the bacterial strain of biofilm-forming methicillin-resistant S.aureus (BF-MRSA), using Fetal Bovine Serum (FBS) as a culture medium, and cultivated at 37°C. In the JIS Z2801 test, Antibacterial activity values of the HA-Ag disk were composed against E.coli 4.1 and S.aureus 5.0. In the modified JIS Z2801 test, antibacterial activity values against E.coli, S.aureus and BF-MRSA were 8.2, 5.5, and 7.1. When this value is greater than 2.0, it shows there is antibacterial activity. The titanium disk coated with HA-Ag showed antibacterial activity in both tests. The JIS Z2801 test is designed to evaluate comodities in poor nutritional environment. However, the environment in the body is eutrophic. It is easy to make bacterial growth. For this reason, it is necessary to consider evaluating for biomaterials with suitable method considered in vivo. In this study, to examine the condition like that found in the body, we cultivated FBS at 37°C. In addition, the antibacterial activity against BF-MRSA was examined to consider the bacterial infection related to orthopaedic implants. The modified JIS Z2801 test showed that it is a suitable evaluation method for in vitro antibacterial activity of biomaterials

Summary Statement. Magnesium has a number of qualities suitable for bioresorbable metallic implants. However, high corrosion rate and formation of hydrogen gas can compromise its performance. Combining magnesium with calcium phosphate improves magnesium's biocompatibility by decreasing gas formation and increasing bone remodeling. Introduction. Clinical problems like risk of postoperative infection and increased incidence of pediatric trauma requiring surgical intervention raised the need for temporary orthopedic implants that would resorb after the bone healing is complete. This would decrease high costs associated with repeated surgeries, minimise recovery times, decrease the risk of postoperative infections, and thus promote higher quality of life to the patients. The specific requirement for orthopedic implants, aside from being bioresorbable, is the ability to bear high loads. Magnesium was suggested as a suitable material for these purposes because it is biocompatible; has excellent mechanical properties; is natural for human body, and seems to stimulate new bone formation. However, an important problem with magnesium is high corrosion rate with consistent hydrogen gas formation on contact with fluids. This in vivo study focuses on investigation of new magnesium-based implants specifically designed to minimise hydrogen gas formation. Methods. Four types of degradable magnesium-based materials were tested for biocompatibility in this study: Magnesium-Hydroxyapatite implants (Mg-HA); Magnesium-Calcium Phosphate Cement (Mg-CPC); alloy of 96% Magnesium and 4% Yttrium (W4); and 99.95% pure magnesium which was a control group. Biomaterials were operated into 33 male New Zealand white rabbits. The animals were sacrificed after 6 and 12 weeks after which the samples were embedded into Epon, paraffin and Technovit resin. The staining was done with TRAP, hematoxylin eosin and toluidine blue. Additionally, TEM and immunohistochemical analysis were performed. The data was analysed both qualitatively and quantitatively by Statistical Package for the Social Sciences (SPSS, v18, SPSS Inc, Chicago, IL). Results. Mg-CPC showed the best performance in this study. New bone formation was significantly more prevalent in Mg-CPC group while gas formation was significantly less comparing to the other materials. Mg-HA had the worst properties due to extremely fast degradation already at 6 weeks, the least amount of new bone formation, and the lowest amount of osteoclasts and multinucleated cells in the implantation site. Pure magnesium and W4 had similar properties: both were surrounded with corrosion layer, and the gas volumes were significantly higher in these two groups compared to other materials. Discussion/Conclusion. New bone was seen forming either in direct contact to implants or around the gas bubbles. The later can be interpreted as body's reaction to protect from gas spreading. Mg-HA's degradation rate was far too fast and this is unacceptable for orthopedic fractures which often require several months to heal and that experience much load. Pure magnesium and W4 although maintained their integrity, were surrounded by corrosion layer and gas bubbles that were bigger in diameter than in the other groups. These findings could compromise implant stability. Mg-CPC was the most biocompatible; it showed significantly higher amount of osteoclasts which is a first sign of bone remodeling. It had also significantly less gas production than other groups. These results show that magnesium's biocompatibility could be improved by combining it with other suitable materials, such as calcium phosphate

Metal on metal hip replacements have been one of worst failures in recent years in terms of orthopaedic implants. Some of these devices have had catastrophic failure rates, with reports of 48% failure at 6 years. The failure of these devices has led to considerable suffering, pain and reduction in quality of life; consequently, they have given rise to high costs and multi-million-dollar legal cases. This talk will describe the history of the current metal on metal failure and discuss some of the reasons why might have occurred. It will also consider the reasons that wear debris arising from the trunnion is worse in terms of biological activity then that arising from the bearing surfaces

We present two cases of metastatic lung cancer which occurred at the site of a previously united tibial fracture. Both patients were treated with a locked intramedullary nail. The patients presented with metastases at the site of their initial fracture approximately 16 and 13 months after injury respectively. We discuss this unusual presentation and review the relevant literature. We are unaware of any previous reports of a metastatic tumour occurring at the site of an orthopaedic implant used to stabilise a non-pathological fracture. These cases demonstrate the similar clinical presentation of infection and malignancy: a diagnosis which should always be considered in such patients

Porous surfaces on orthopaedic implants have been shown to promote tissue ingrowth. This study evaluated biological fixation of novel additively manufactured porous implants with and without hydroxyapatite coatings in a canine transcortical model. Laser rapid manufacturing (LRM) Ti6Al4V cylindrical implants were built with a random interconnected architecture mimicking cancellous bone (5.2 mm diameter, 10mm length, 50–60% porous, mean pore size 450μm). Three groups were investigated in this study: as-built with no coating (LRM), as-built coated with solution precipitated hydroxyapatite (LRM-PA), and as-built coated with a plasma sprayed hydroxyapatite (LRM-PSHA). Implants were press-fit into a 5mm unicortical, perpendicular drill hole in the femoral diaphysis of the left and right femurs in 12 canines. Right femora were harvested for histology (SEM, bone ingrowth into implant within cortical region) and left femora for mechanical push-out testing (shear strength of bone-implant interface) at 4 and 12 weeks (N=6, un-paired Student's t-test, p=0.05). For mean bone ingrowth, there was no significant difference between groups at 4 weeks (LRM, LRM-PA, LRM-PSHA: 41.5+8.6%, 51+5.5% and 53.2+11%, respectively) or 12 weeks (LRM, LRM-PA, LRM-PSHA: 64.4+2.8%, 59.9+7.6%, 64.9+6.4%, respectively). LRM and LRM-PA implants had more bone ingrowth at 12 weeks than 4 weeks (p < 0 .05). Mean shear strength of all implants at 12 weeks (LRM, LRM-PA, LRM-PSHA: 39.9+3.6MPa, 33.7+4.6MPa, 36+4.1MPa respectively) were greater than at 4 weeks (LRM, LRM-PA, LRM-PSHA: 21.6+2.8MPa, 20.7+1.1MPa, 20.2+2.5MPa respectively) (p < 0 .05). No significant difference was observed between all groups at 4 or 12 weeks. Overall, this canine study confirmed the suitability of this novel additive manufacturing porous material for biological fixation by bone ingrowth. All implants exhibited high bone ingrowth and mechanical shear strength in this canine model. No difference was observed between uncoated and hydroxyapatite coated implants

Regulatory bodies impose stringent pre-market controls to certify the safety and compatibility of medical devices. However, internationally recognized standard tests may be expensive, time consuming and challenging for orthopedic implants because of many possible sizes and configurations. In addition, cost and time of standard testing may endanger the feasibility of custom-device production obtained through innovative manufacturing technologies like 3d printing. Modeling and simulation (M&S) tools could be used by manufactures and at point-of-care to improve design confidence and reliability, accelerate design cycles and processes, and optimize the amount of physical testing to be conducted. We propose an integrated cloud platform to perform in silico testing for orthopedic devices, assessing mechanical safety and electromagnetic compatibility, in line with recognized standards and regulatory guidelines. The . InSilicoTrials.com. platform contains two M&S tools for orthopedic devices: CONSELF and NuMRis. CONSELF (. conself.com. ) uses Salome-Meca 2017 to compute static implant stresses and strains on metallic orthopedic devices, following the requirements and considerations of ASTM F2996-20 for non-modular hip femoral stems and ASTM F3161-16 for total knee femoral components. Simulation results were consistent with those reported in the two standards. NuMRis (. numris.insilicomri.com. ) uses ANSYS HFSS and ANSYS Mechanical 2019R3 to compute radio-frequency energy absorption and induced heating in 1.5T and 3T MRI coils, replicating the ASTM F2182-19e2 Standard Test Method. Simulation results were validated against in vitro measurements. The integrated M&S workflow on the cloud platform allows the user to upload the 3D geometry and the material properties of the orthopedic device to be tested, automatically set up the standard testing scenarios, run simulations and process outcome, with the option to summarize the results in accordance with current FDA guidance on M&S reporting. The easy-to-use interfaces of InSilicoTrials tools run through commercial web browsers, requiring no specific expertise in computational methods or additional on-premise software and hardware resources, since all simulations are run remotely on cloud infrastructure. The integrated cloud platform can be used to evaluate design alternatives, test multi-configuration devices, perform multi-objective design optimization and identify worst-case scenarios within a family of implant sizes, or to assess the safety and compatibility of custom-made orthopedic devices. InSilicoTrials.com. is the first cloud platform offering a collection of M&S tools to perform in silico standard testing for orthopedic devices. The proposed tools allow to assess mechanical safety and electromagnetic compatibility before prototyping, preventing risks and criticalities for the patient, and helping manufacturers and point-of-care to accelerate time and reduce costs during the device development. The proposed platform promotes the broader adoption of digital evidence in preclinical trials, supporting the device submission process and pre-market regulatory evaluation, and helping secure regulatory approval

Introduction. According to American Joint Replacement Registry, particle mediated osteolysis represents 13 % of the knee revision surgeries performed in the United States. The comprehension of mechanical and wear properties of materials envisioned for TJR is a key step in product development. Furthermore, the maintenance of UHMWPE mechanical properties after material modification is an important aspect of material success. Initial studies conducted by our research group demonstrated that the incorporation of ibuprofen in UHMWPE had a minor impact on UHMWPE physicochemical and mechanical properties. Drug release was also evaluated and resulted in an interesting profile as a material to be used as an anti-inflammatory system. Therefore, the present study investigated the effect of drug release on the mechanical and biological properties of ibuprofen-loaded UHMWPE. Experimental. UHMWPE resin GUR 1020 from Ticona was for sample preparation. Samples with drug concentrations of 3% and 5% wt were consolidated as well as samples without anti-inflammatory addition through compression molding at 150 °C and 5 MPa for 15 minutes. Mechanical properties were evaluated via the tensile strength experiment (ASTM D638) and dynamic mechanic tests. Wear resistance was measured using the pin on disc (POD) apparatus. Finally, cytotoxicity analysis was conducted based on ISO 10993–5. Results. Dynamic-mechanic analysis demonstrated no difference in flexion modulus and stress for all materials (Table 1). No difference was also verified during cyclical loading experiments (Table 1), which indicates that the drug concentration added to material composition did not affect these properties. POD experiments were proposed to evaluate wear resistance of ibuprofen-loaded UHMWPE samples considering the combination of materials similar to those employed in TJR. Results from POD tests are presented in Table 1. Volumetric wear was close to zero for all samples after 200 thousand cycles. Comprehension of the effect of drug release on mechanical properties is essential to estimate how the material will behave after implantation. Therefore, mechanical properties were assessed after 30 days of ibuprofen release and the results were compared with those obtained in samples as prepared (Table 2). Initial results demonstrated a decrease in elastic modulus in samples prepared with ibuprofen. However, no difference was verified between UHMWPE, UHMWPE 3% IBU and UHMWPE 5% IBU after ibuprofen release. Finally, cell viability of UHMWPE 3% IBU and UHMWPE 5% was found to be superior to 100% (Figure 1). Therefore, both materials can be considered nontoxic. Conclusions. Ibuprofen-loaded UHMWPE did not demonstrate a significant influence on the mechanical and biological behavior of UHMWPE. Dynamic-mechanical tests demonstrated constancy for all samples under analysis. Wear testing resulted in gravimetric wear close to zero, for all tested materials. Mechanical properties conducted after 30 days of ibuprofen release also had a positive outcome. Although presenting a difference in modulus prior and after release tests, modulus and tensile yield stress remained inside acceptable range indicated to UHMWPE used in orthopedic implants. Furthermore, after drug elution UHMWPE 3% IBU and UHMWPE 5% IBU recovered original UHMWPE properties. Cytotoxicity assessment was performed and both ibuprofen-based formulations were considered nontoxic according to ISO 10993–5. For any figures or tables, please contact the authors directly

After the first big hype on additive manufacturing in medical industry the technology of 3D printing is now reaching a productive stage for some selected applications. These applications range from surgical models for visualisation to patient-specific cutting guides and 3D printed orthopaedic implants. This presentation will guide through current 3D printing applications in medical devices. We will show success stories for products in some of these fields and try to point out to a potential future of fully personalized orthopaedics in polymer and metals. A regulatory view on all aspects of 3D printing will be presented and potential hurdles to expand the full potential of medical device 3D printing

Objectives. The monitoring of fracture healing is a complex process. Typically, successive radiographs are performed and an emerging calcification of the fracture area is evaluated. The aim of this study was to investigate whether different bone healing patterns can be distinguished using a telemetric instrumented femoral internal plate fixator. Materials and Methods. An electronic telemetric system was developed to assess bone healing mechanically. The system consists of a telemetry module which is applied to an internal locking plate fixator, an external reader device, a sensor for measuring externally applied load and a laptop computer with processing software. By correlation between externally applied load and load measured in the implant, the elasticity of the osteosynthesis is calculated. The elasticity decreases with ongoing consolidation of a fracture or nonunion and is an appropriate parameter for the course of bone healing. At our centre, clinical application has been performed in 56 patients suffering nonunion or fracture of the femur. Results. A total of 39 cases of clinical application were reviewed for this study. In total, four different types of healing curves were observed: fast healing; slow healing; plateau followed by healing; and non-healing. Conclusion. The electronically instrumented internal fixator proved to be valuable for the assessment of bone healing in difficult healing situations. Cost-effective manufacturing is possible because the used electronic components are derived from large-scale production. The incorporation of microelectronics into orthopaedic implants will be an important innovation in future clinical care. Cite this article: B. Kienast, B. Kowald, K. Seide, M. Aljudaibi, M. Faschingbauer, C. Juergens, J. Gille. An electronically instrumented internal fixator for the assessment of bone healing. Bone Joint Res 2016;5:191–197. DOI: 10.1302/2046-3758.55.2000611

Orthopaedic implants, such as femoral heads, sockets and stems, are manufactured with a high degree of smoothness and very low form error in order to function as low wear bearings. The surfaces are subject to both wear and damage during in vivo use. Articulating surfaces naturally wear during normal use. Aseptic loosening associated with osteolysis and release of wear particles is the main reason for revision of total hip arthroplasty (THA). Damage of femoral heads is well known to increase the wear rate at the articulating surface and is vulnerable to scratching during the maneuver of positioning the femoral component into the acetabulum component either in primary as in revision total hip arthroplasties. The findings emphasize the importance of achieving and maintaining good surface finish of the femoral head component. The author presents a very simple and “zero cost” method of preventing scratching of the femoral head of any kind of total hip prosthesis (ceramic on ceramic, ceramic on poly, metal on metal, metal on poly and even metal on ceramic) when the reduction of the femoral head prosthesis is done inside the new acetabular component with metal, ceramic liner or poly liner with metal back (where the scratching can also occur) as one of the final stages of the surgical procedure which can be crucial to the long survival of the hip prosthesis. A short one minute video on an e-poster will show how this can be done being an easy, reproducible, safe and reliable technique to prevent femoral head scratching

Nanotechnology is the study, production and controlled manipulation of materials with a grain size < 100 nm. At this level, the laws of classical mechanics fall away and those of quantum mechanics take over, resulting in unique behaviour of matter in terms of melting point, conductivity and reactivity. Additionally, and likely more significant, as grain size decreases, the ratio of surface area to volume drastically increases, allowing for greater interaction between implants and the surrounding cellular environment. This favourable increase in surface area plays an important role in mesenchymal cell differentiation and ultimately bone–implant interactions. Basic science and translational research have revealed important potential applications for nanotechnology in orthopaedic surgery, particularly with regard to improving the interaction between implants and host bone. Nanophase materials more closely match the architecture of native trabecular bone, thereby greatly improving the osseo-integration of orthopaedic implants. Nanophase-coated prostheses can also reduce bacterial adhesion more than conventionally surfaced prostheses. Nanophase selenium has shown great promise when used for tumour reconstructions, as has nanophase silver in the management of traumatic wounds. Nanophase silver may significantly improve healing of peripheral nerve injuries, and nanophase gold has powerful anti-inflammatory effects on tendon inflammation. . Considerable advances must be made in our understanding of the potential health risks of production, implantation and wear patterns of nanophase devices before they are approved for clinical use. Their potential, however, is considerable, and is likely to benefit us all in the future. Cite this article: Bone Joint J 2014; 96-B: 569–73

In the vast majority of patients, the anatomical and mechanical axes of the tibia in the coronal plane are widely accepted to be equivalent. This philosophy guides the design and placement of orthopaedic implants within the tibia and in both the knee and ankle joints. However, the presence of coronal tibial bowing may result in a difference between these two axes and hence cause suboptimal placement of implanted prostheses. Although the prevalence of tibial bowing in adults has been reported in Asian populations, to date no exploration of this phenomenon in a Western population has been conducted. The aim of this study was to quantify the prevalence of coronal tibial bowing in a Western population. This was an observational retrospective cohort study using anteroposterior long leg radiographs collected prior to total knee arthroplasty in our high volume arthroplasty unit. Radiographs were reviewed using a Picture Archiving and Communication System. Using a technique previously described in the literature for assessment of tibial bowing, two lines were drawn, each one third of the length of the tibia. The first line was drawn between the tibial spines and the centre of the proximal third of the tibial medullary canal. The second was drawn from the midpoint of the talar dome to the centre of the distal third of the tibial medullary canal. The angle subtended by these two lines was used to determine the presence of bowing. Bowing was deemed significant if more than two degrees. The position of the apex of the bow determined whether it was medial or lateral. Measurements were conducted by a single observer and 10% of measurements were repeated by the same observer and also by two separate observers to allow calculation of intraclass correlation coefficients (ICCs). A total of 975 radiographs consecutively performed in the calendar years 2015–16 were reviewed, 485 of the left leg and 490 of the right. In total 399 (40.9%) tibiae were deemed to have bowing more than two degrees. 232 (23.8%) tibiae were bowed medially and 167 (17.1%) were bowed laterally. The mean bowing angle was 3.51° (s.d. 1.24°) medially and 3.52° (s.d. 1.33°) laterally. Twenty-three patients in each group (9.9% medial/13.7% lateral) were bowed more than five degrees. The distribution of bowing angles followed a normal distribution, with the maximal angle observed 10.45° medially and 9.74° laterally. An intraobserver ICC of 0.97 and a mean interobserver ICC of 0.77 were calculated, indicating excellent reliability. This is the first study reporting the prevalence of tibial bowing in a Western population. In a significant proportion of our sample, there was divergence between the anatomical and mechanical axes of the tibia. This finding has implications for both the design and implantation of orthopaedic prostheses, particularly in total knee arthroplasty. Further research is necessary to investigate whether prosthetic implantation based on the mechanical axis in bowed tibias results in suboptimal implant placement and adverse clinical outcomes

Formation of micro-cracks occurs in bone due to daily activities. Through a mechanism of self-repair, these micro-cracks are detected, and the damaged areas are restored, avoiding further propagation. The Scissors Model suggests that the osteocyte processes that cross the micro-cracks break as consequence of the cyclic displacements of the micro-crack faces, due to fatigue, and this triggers the remodelling processes. A fresh bovine tibia bone was cut in sections oriented 20° from the transversal direction. The cortical bone was sliced using a circular saw and shaped to the dimensions: 20 × 10 × 1 (mm) and the surfaces were polished. µCT images were obtained from all the samples (μCT 40, Scanco Medical, Brüttisellen, Switzerland). From the DICOM files, the geometries were reconstructed and meshed using tetrahedrons, in ICEM CFD. The Elasticity Modulus (E) was determined in Bonemat, by applying an empirical relationship Elasticity-Density from the literature. The parts were then imported into ANSYS APDL to simulate micro-crack propagation in bone. This model will be validated with further experimental work where the micro-crack will be initiated in the prepared samples and propagated due to fatigue loading, and the osteocyte processes will be visualized in the Scanning Electron Microscope (SEM). This investigation aims to study how cyclic loading in bones and failure of osteocyte processes can trigger target the mechanism of bone remodelling. The resulting model can later contribute for the investigation of treatments for bone diseases such as osteoporosis and the response of bone to the presence of orthopaedic implants

Additive Manufacturing techniques such as Selective laser melting (SLM) are increasingly used in the fabrication of hip, knee and other orthopaedic implants. This is due to the ability of these techniques to print geometrically complex parts with osteoconductive features, resulting in a decreased chance of aseptic loosening. To facilitate wider adoption of SLM, in-situ process monitoring is required. This paper examines the robustness of a novel monitoring systems ability to detect voids within the bulk of a component with varying part density. This work reports the results of a printing study carried out with Ti6Al4V parts using a production scale Renishaw system. This system is equipped with the recently developed in-situ monitoring system, called InfiniAM Spectral. InfiniAM measures the level of optical emissions emitted during the build process. The Spectral software creates a 3D representation of the part, in near real time, based on the level of emissions detected. In this work, Spectral 3D images are compared with those generated after printing using a micro CT scanner. The latter creates a virtual 3D representation of the part and has the ability to detect part defects and voids, as well as quantify part density, within the body of a component. In this work, parts were designed with voids of diameters in the range 200 to 600 μm. The sensitivity of the in-situ monitoring system was correlated with post process analysis of the void dimensions. Additionally, the detection of part density variation due to a variation of input energy, was also evaluated

Perioperative infections can cause devastating results, especially in cases employing endoprostheses and/or allografts. To minimize bacterial contamination and thereby decrease infection rates, a series of experiments was performed to determine the role of several factors on intraoperative contamination. In an initial pilot study, 102 surgical team members participating in clean orthopaedic cases were prospectively randomized to exchange or not exchange their outer pair of gloves one hour into the surgical procedures. Rodac plate cultures of the surgeon’s dominant gloved hand and of his or her gown sleeve were taken at baseline and again 15 minutes after potential glove exchange. The surgical gown type (reusable cloth versus disposable paper) utilized in each case was recorded. An unexpected overwhelming effect of gown type on bacterial contamination rates was detected, which overpowered any effect of glove exchange. The outer glove exchange experiment was then repeated with 251 prospectively randomized surgical team members, with all team members utilizing only disposable paper gowns. Otherwise the experimental protocol was the same. A final experiment was devised to test bacterial strike through of the two gown types. A standardized suspension (3 ml of coagulase negative staphylococcus containing 108 bacteria/ml) was applied to one side of the test materials and compressed with a 10 lb. weight. A rodac culture plate was applied to the opposite side of the material to determine bacterial strike through rates utilizing previously validated methodology. The initial pilot experiment revealed a baseline sleeve culture positive rate of 41% with cloth gowns versus only 13% with disposable gowns (p=0.002, Students t-test). Cultures of the glove one hour and fifteen minutes into the operations revealed a 31% culture positive rate with reusable cloth gowns versus only 7% with disposable gowns (p=0.001), with a 4.38 x odds ratio. There was no statistically significant difference in the glove culture positive rate at one hour and fifteen minutes based on glove exchange (19% with glove retention vs. 10% following glove exchange p=0.19). There was no statistically significant difference in the culture positive rate between the two gown types when tested straight out of their sterile packaging (reusable gowns two positive cultures out of 50 cultures, disposable gowns zero positive cultures out of 50 cultures). On the second glove exchange experiment, surgeons exchanging gloves one hour into the case had a positive glove contamination rate of 13% compared to 23% in those retaining their original glove (p=0.04 Student’s t-test, odds ratio 0.51). The bacterial strike through study revealed that 22 of 25 cloth gowns allowed transmission of bacteria, whereas only 1 of 25 disposable paper gowns allowed transmission of bacteria (p=0.001, nonparametric sign rank test). The choice of gown type had the greatest effect on the intraoperative culture positive rate of the surgeon’s dominant hand glove in our studies. Based on these results, at our institution, all orthopaedic surgeons now utilize only disposable paper gowns on all cases employing allograft or endoprosthesis implantation. We strongly recommend that only disposable paper gowns be utilized for any case with any orthopaedic implant materials and such gowns should be considered for all surgical cases. Exchange of the surgeon’s outer gloves prior to handling orthopaedic implant devices, especially if an hour of operating time has already elapsed, is also a recommended and prudent practice to diminish intraoperative contamination of the implant materials. The utilization of disposable drapes in addition to disposable gowns is also recommended due to the lower likelihood of bacterial strike through with currently available disposable synthetic materials. Following these recommended guidelines should help surgeons minimize the risk of intraoperative contamination and should thereby reduce the rate of infections

Background. Method of fixation in THA is a contentious issue, with proponents of either technique citing improved implant survival and outcomes. Current comparisons rely on insufficiently powered studies with short-term follow up or larger poorly controlled registry studies. Patient factors are considered a key variable contributing to the risk of implant failure. One way to overcome this confounder is to compare the survival of cementless and cemented THAs patients who have undergone bilateral THAs with cemented hip on one side and cementless hip on the other. We compared stem survival of patients who have bilateral THA with one cemented stem in one hip and a cementless stem in the contralateral hip in the National Joint Registry. Methods. UK National Joint Registry is the largest registry of its kind in the world. This study included 2934 patients with 5868 THAs who underwent bilateral THAs s between 2003 and 2016. These patients had undergone bilateral sequential THAs within 3 years of each other: cemented THA on one side and cementless on the other, Patients had identical pre-operative American Society of Anaesthesiologists group for both THAs and same indication for surgery. Implant survival was compared using Cox regression with an endpoint of stem revision. Results. Ten-year all-cause survival of cementless stems was lower than for cemented stems (p<0.001), as was survival to aseptic loosening revision (p<0.001). Similar trends were seen across all age groups including young and old patients. There was a non-significant trend towards superiority of cemented stems in survival until periprosthetic fracture, dislocation and infection. Conclusion. Comparison of cementless with cemented stems within patients is a novel method to compare the outcomes of orthopaedic implants. Survival was better for cemented stems including for younger patients and aseptic loosening

Each year more than 70 billion standard units of antibiotic are prescribed to treat bacterial infections worldwide. In addition, at least 63,000 tons of antibiotics are consumed by livestock for growth promotion and disease prevention. The result of this overuse of antibiotics is a spiraling increase in resistance. In the United States and Europe, antibiotic resistant bacteria are responsible for more than 4 million infections and approximately 50,000 deaths annually. In addition, bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) have increased in prevalence in hospitals over the last three decades. Such bacteria are particularly problematic in postoperative infections, exacerbating treatment through the development of biofilms, especially on medical implants which are virtually impossible to treat without removal and replacement of the device. This presentation will show how non-invasive preclinical imaging (optical, PET and CT) is being used to better understand the establishment and development of bacterial infections in vivo, and how best to treat them. In particular, data will be shown as to how preclinical imaging can be used to monitor bacterial infections on orthopaedic implants, and how this technology might be translated into the clinic

The main problem of infected orthopaedic implants is that the presence of microorganisms in an organized biofilm making them difficult accessible for antibiotics. This biofilm consists of a complex community of microorganisms embedded in an extracellular matrix that forms on surfaces such as an implant. Non-contact induction heating uses pulsed electromagnetic fields to induce so-called ‘eddy currents’ within metal objects which causes them to heat up. This heat causes thermal damage to the bacterial biofilm hence killing the bacteria on the metal implant. The purpose of this study is to determine the effectiveness of induction heating on killing Staphylococcus epidermidis in a biofilm. S. epidermidis biofilms were grown on Titanium alloy (Ti6Al4V) coupons and subsequently were heated with a custom-built induction heater to temperatures of 60°C, 70°C, 80°C and 90°C for 3.5 minutes. Temperature was controlled with an infra-red thermal sensor and micro-controller. We also included two control conditions without induction heating: C1 without induction heating and C2 with chlorhexidine 0.5% in 70% alcohol without induction heating. Experiments were repeated 5 times. In the C1 group (no induction heating), 1.3 * 10(7) colony forming units (CFU)/cm(−2) of S. epidermidis were observed. For 60°C, 70C, 80 C and 90C, a 3.9-log reduction, 5.3-log reduction, 5.5-log reduction and 6.1-log reduction in CFU/cm(−2) were observed, respectively. For the C2 (chlorhexidine) there was a 6.7-log reduction CFU/cm(-2). We concluded that induction heating of Titanium coupons is effective in reducing bacterial load in vitro for S. epidermidis biofilms