Modular hip prostheses were introduced to optimize the intra-surgical adaptation of the implant design to the native anatomy und biomechanics of the hip. The downside of a modular implant design with an additional modular interface is the potential susceptibility to fretting, crevice corrosion and wear. For testing hip implants with proximal femoral modularity according to ISO & ASTM, sodium chloride solutions are frequently used to determine the fatigue strength and durability of the stem-neck connection. The present study illustrate that the expansion of standard requirements of biomechanical testing is necessary to simulate metal ion release as well as fretting and crevice corrosion by using alternative test fluids. To assess the primary stability of tibial plateaus in vitro, different approaches had been undergone: cement penetration depth analysis, static tension or compression loading until interface failure. However, these test conditions do not reflect the in vivo physiologic loading modes, where the tibial plateau is predominantly subjected to combined compression and shear forces. The objectives were to evaluate the impact of the tibial keel & stem length on the primary stability of a posterior-stabilised tibial plateau under dynamic compression-shear loading conditions in human tibiae.

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

Abstract. Objectives. Additive manufacturing has led to numerous innovations in orthopaedic surgery: surgical guides; surface coatings/textures; and custom implants. Most contemporary implants are made from titanium alloy (Ti-6Al-4V). Despite being widely available industrially and clinically, there is little published information on the performance of this 3D printed material for orthopaedic devices with respect to regulatory approval. The aim of this study was to document the mechanical, chemical and biological properties of selective laser sintering (SLS) manufactured specimens following medical device (TOKA®, 3D Metal Printing LTD, UK) submission and review by the UK Medicines and Healthcare Products Regulatory Agency (MHRA). Methods. All specimens were additively manufactured in Ti-6Al-4V ELI (Renishaw plc, UK). Mechanical tests were performed according to ISO6892-1, ISO9585 and ISO12107 for tensile (n=10), bending (n=3) and fatigue (n=16) respectively (University of Bath, UK). Appropriate chemical characterisation and biological tests were selected according to recommendations in ISO10993 and conducted by external laboratories (Wickham Labs, UK; Lucideon, UK; Edwards Analytical, UK) in adherence with Good Lab Practise guidelines. A toxicological review was conducted on the findings (Bibra, UK). Results. The mechanical tests demonstrated that the material performed to the specification for conventionally manufactured titanium alloy of this type (ISO5832-3). The toxicology review concluded that there were no significant concerns for the health of the patients identified in this evaluation and implantation of the TOKA® device would not result in a significant health risk to patients. Conclusions. Reflecting on our MHRA experience, additive manufacture of orthopaedic devices is still considered to be a ‘novel’ process by regulatory bodies, requiring additional safety evidence. Despite this, our findings demonstrate that there is no difference, mechanically or chemically, to the traditionally manufactured alloy material. We hope to support the widening use of 3D printed titanium alloy orthopaedic devices by publishing our route to regulatory approval. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Orthopedic Device-Related Infections (ODRIs) are a major medical challenge, particularly due to the involvement of biofilm-encased and multidrug-resistant bacteria. Current treatments, based on antibiotic administration, have proven to be ineffective. Consequently, there is a need for antibiotic-free alternatives. Antimicrobial peptides (AMPs) are a promising solution due to their broad-spectrum of activity, high efficacy at very low concentrations, and low propensity to induce resistance. We aim to develop a new AMP-based chitosan nanogel to be injected during orthopedic device implantation to prevent ODRIs. Chitosan was functionalized with norbornenes (NorChit) through the reaction with carbic anhydride and then, a cysteine-modified AMP, Dhvar5, a peptide with potent antibacterial activity, even against methicillin-resistant Staphylococcus aureus (MRSA), was covalently conjugated to NorChit (NorChit- Dhvar5), through a thiol-norbornene photoclick chemistry (UV= 365 nm). For NorChit-Dhvar5 nanogels production, the NorChit-Dhvar5 solution (0.15% w/v) and Milli-Q water were injected separately into microfluidic system. The nanogels were characterized regarding size, concentration, and shape, using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and Dynamic light scattering (DLS). The nanogels antibacterial properties were assessed in Phosphate Buffer (PBS) for 6 h, against four relevant microorganisms (Pseudomonas aeruginosa, S. aureus and MRSA, and in Muller- Hinton Broth (MHB), 50% (v/v) in PBS, supplemented with human plasma (1% (v/v)), for 6 and 24 h against MRSA. The obtained NorChit-Dhvar5 nanogels, presented a round-shaped and ∼100 nm. NorChit- Dhvar5 nanogels in a concentration of 10. 10. nanogels/mL in PBS were capable of reducing the initial inoculum of P. aeruginosa by 99%, S. aureus by 99%, and MRSA by 90%. These results were corroborated by a 99% MRSA reduction, after 24 h in medium. Furthermore, NorChit-Dhvar5 nanogels do not demonstrate signs of cytotoxicity against MC3T3-E1 cells (a pre-osteoblast cell line) after 14 days, having high potential to prevent antibiotic-resistant infection in the context of ODRIs

Biomaterials are no longer considered innate structures and using functionalisation strategies to modulate a desired response whether it is a host or implant is currently an important focus in current research paradigms. Fundamentally, a thorough understanding the host response will enable us to design proper functionalisation strategies. The input from the host response need to be weighed in depending on the host disease condition. In addition, biomaterials themselves provide immense therapeutic benefits which needs to be accounted for when using functionalisation strategies. Using strategies such as enzymatic and hyperbranched linking systems, we have been able to link biomolecules to different structural moieties. Our recent design efforts have harnessed the therapeutic effects of biomaterials and mapped the molecular fingerprint of this specific host response in a disease target. This approach allows us to rethink functionalisation strategies currently employed in the field. This talk will elucidate some of these ongoing strategies that have applications in the development of the next generation of orthopaedics devices

For decades, universities and research centers have been applying modeling and simulation (M&S) to problems involving health and medicine, coining the expression in silico clinical trials. However, its use is still limited to a restricted pool of specialists. It is here proposed an easy-to-use cloud-based platform that aims to create a collaborative marketplace for M&S in orthopedics, where developers and model creators are able to capitalize on their work while protecting their intellectual property (IP), and researcher, surgeons and medical device companies can use M&S to accelerate time and to reduce costs of their research and development (R&D) processes. Digital libraries on . InSilicoTrials.com. are built on collaborations among first-rate research center, model developers, software, and cloud providers (partners). Their access is provided to life science and healthcare companies, clinical centers, and research institutes (users), offering them with several solutions for the different steps of the orthopedics and medical devices R&D process. The platform is built using the Microsoft Azure cloud services, conforming to global standards of security and privacy for healthcare, ensuring that clinical data is properly managed, protected, and kept private. The environment protects the IP of partners against the downloading, copying, and changing of their M&S solutions; while providing a safe environment for users to seamlessly upload their own data, set up and run simulations, analyze results, and produce reports in conformity with regulatory requirements. The proposed platform allows exploitation of M&S through a Software-as-a-Service delivery model. The pay-per-use pricing: 1. provide partners with a strong incentive to commercialize their high-quality M&S solutions; 2. enable users with limited budget, such as small companies, research centers and hospitals, to use advanced M&S solutions. Pricing of the M&S tools is based on specific aspects, such as particular features and computational power required, in agreement with the developing partner, and is distinct for different types of customers (i.e., academia or industry). The first medical devices application hosted on . InSilicoTrials.com. is NuMRis (Numerical Magnetic Resonance Implant Safety), implemented in collaboration with the U.S. F.D.A. Center for Devices and Radiological Health, and ANSYS, Inc. The automatic tool allows the investigation of radiofrequency (RF)-induced heating of passive medical implants, such as orthopedic devices (e.g., rods and screws), pain management devices (e.g., leads), and cardiovascular devices (e.g., stents), following the ASTM F2182-19e2 Standard Test Method. NuMRis promotes the broader adoption of digital evidence in preclinical trials for RF safety analysis, supporting the device submission process and pre-market regulatory evaluation. InSilicoTrials.com. aims at defining a new collaborative framework in healthcare, engaging research centers to safely commercialize their IP, i.e., model templates, simulation tools and virtual patients, by helping clinicians and healthcare companies to significantly expedite the pre-clinical and clinical development phases, and to move across the regulatory approval and HTA processes

AM specifically allows for cost-efficient production of patient-specific Orthopaedic medical devices with unusual designs and properties. A porous design allows to adjust the stiffness of metallic implants to that of the host bone. Beyond traditional metals, like titanium alloys, this talk will review the present state-of-the-art of directly printed absorbable metal families. Physicochemical, mechanical and biological properties of standardized design prototypes from all currently available metal families will be compared and their clinical application potential discussed. The impact of in vitro test environments on comparative corrosion behavior, post manufacturing aspects, and the recent status quo in biocompatibility testing and present knowledge gaps will be addressed

Prosthetic Joint Infections (PJIs) are increasing with the use of orthopedic devices on an ageing population. Cutibacterium acnes is a commensal organism that plays an important role in the ecosystem healthy human skin, yet this species is also recognized as a pathogen in foreign body infection: endocarditis, prostatitis and specifically in PJIs. C. acnes is able to escape the immune system. This phenomenon could reflect two bacterial behaviour: the bacterial internalization by host cells and the biofilm formation. In this study, we studied different clinical strains of C. acnes. We noticed that C. acnes isolated from PJIs form 2 fold-more biofilm than the strains isolated from a normal skin in two models (Crystal violet staining and fluorescent microscopy (p=0.04 and p=0.02, respectively, Mann-Whitney test). We did not observe any difference in the internalization rate of those strains by osteoblasts. However, the quantity of biofilm formed by C. acnes before and after the internalization was compared. A significant increase in biofilm formation was observed for the strains isolated from the skin (x2.3±0.07; p=0.008, Mann-Whitney test). However, the hydrophobicity of the skin strains is significantly less important than for the PJIs strains (24.8±13% vs 56.6±12% respectively; p=0.003, Mann-Whitney test) but this did not change after internalization suggesting that there is no cell wall evolution. In conclusion, we studied for the first time the impact of bacterial internalization by osteoblasts on the virulent behaviour of C. acnes, which could explain the hided pathogenicity of this commensal bacterium

Since 2010, there has been a sharp decline in the use of metal-on-metal joint replacement devices due to adverse responses associated with the release of metal wear particles and ions in patients. Surface engineered coatings offer an innovative solution to this problem by covering metal implant surfaces with biocompatible and wear resistant materials. The present study tests the hypothesis whether surface engineered coatings can reduce the overall biological impact of a device by investigating recently introduced silicon nitride coatings for joint replacements. Biological responses of peripheral blood mononuclear cells (PBMNCs) to Si3N4 model particles, SiNx coating wear particles and CoCr wear particles were evaluated by testing cytotoxicity, inflammatory cytokine release, oxidative stress and genotoxicity. Clinically relevant wear particles were generated from SiNx-on-SiNx and CoCr-on-CoCr bearing combinations using a multidirectional pin-on-plate tribometer. All particles were heat treated at 180°C for 4 h to destroy endotoxin contamination. Whole peripheral blood was collected from healthy donors (ethics approval BIOSCI 10–108, University of Leeds). The PBMNCs were isolated using Lymphoprep (Stemcell) and incubated with particles at various volumetric concentrations (0.5 to 100 µm3 particles/cell) for 24 h in 5% (v/v) CO2 at 37°C. After incubation, cell viability was measured using the ATPlite assay (Perkin Elmer); TNF-alpha release was measured by ELISA (Invitrogen); oxidative stress was measured using H2DCFDA (Abcam); and DNA damage was measured by comet assay (Tevigen). The results were expressed as mean ± 95% confidence limits and the data was analysed using one-way ANOVA and Tukey-Kramer post-hoc analysis. No evidence of cytotoxicity, oxidative stress, TNF-alpha release, or DNA damage was observed for the silicon nitride particles at any of the doses. However, CoCr wear particles caused cytotoxicity, oxidative stress, TNF-alpha release and DNA damage in PBMNCs at high doses (50 µm3 particles per cell). This study has demonstrated the in-vitro biocompatibility of SiNx coatings with primary human monocytic cells. Therefore, surface engineered coatings have potential to significantly reduce the biological impact of metal components in future orthopaedic devices

Background. Following endosteal uncemented orthopaedic device implantation, the initial implant/bone interface retains spaces and deficiencies further exacerbated by pressure necrosis and resultant bone resorption. This implant-bone space requires native bone infill through the process of de novo osteogenesis. New appositional bone formation on the implant surface is known as contact osteogenesis and is generated by osteogenic cells, including skeletal stem cells (SSCs), colonising the implant surface and depositing the extracellular bone matrix. Surface nanotopographies provide physical cues capable of triggering SSC differentiation into osteoblasts, thus inducing contact osteogenesis, translated clinically into enhanced osseointegration and attainment of secondary stability. The current study has investigated the in vitro and in vivo effects of unique nanotopographical pillar substrates on SSC phenotype and function. Methods. Adult human SSCs were immunoselected, enriched using STRO-1 antibody and cultured on control and test surfaces for 21 days in vitro. The test groups comprised Ti-coated substrates with planar or modified surfaces with nanopillar. Osteoinductive potential was analysed using qPCR and immunostaining to examine gene expression and protein synthesis. Results. Following in vitro (n=5) culture on nanopillars, the expression of osteogenic genes (ALP, Collagen 1, OPN and OCN) and of Osteopontin protein (a bone matrix protein), on Ti pillars were both significantly enhanced when compared to control or Ti planar surfaces. Conclusions. Discrete raised surface nanopillars modulate adult SSC populations in the absence of any chemical cues and enhance their osteogenic properties, an effect not observed on planar Ti constructs. Hence, these findings herald exciting opportunities to improve the implant surface design, implant osseointegration, and, ultimately, implant survival. Level of evidence. Original experimental study

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

Medical grade polyurethanes have been widely promoted for biomedical applications. In particular, the use of polycarbonate-urethanes (PCU) has drawn considerable attention in the orthopaedic device industry as a result of their excellent mechanical properties, biostability and biocompatibility. PCUs have been extensively utilized in vascular grafts, stents and artificial heart valves. Specifically, bionate thermoplastic PCU, commercially produced by DSM PTG (Berkeley, California), has been of great interest in the field of orthopaedics because of its outstanding load-bearing properties and excellent wear resistance. Also, it is characterized by its long-term durability and resistance to hydrolytic degradation making it a good candidate for in-vivo orthopaedic applications. PCUs have been considered for meniscal replacement because of its unique weight-bearing capabilities, ability to withstand intense forces within the knee joint and ease of lubrication due to its hydrophilic nature. In addition, the low frictional properties essential for a meniscal replacement is obtainable with PCUs. Materials used for this study were a commercial polycarbonate-urethanes, Bionate PCU 80A (B8) and 90A (B9) pellets, and polyethylene continuous strands fibres (PE) obtained from DSM Polymer Technology Group, USA. Some quantity of the B8 and B9 pellets were dried separately in a vacuum oven at 100°C for 14 hours. A custom mould was designed for the production of the mechanical test samples. The quantity of the constituent materials was determined using composite theory known as the Rule of Mixtures. E. c. =. E. m. V. m. +. E. f. E. f. where V. m. and V. f. are the volume fraction of the matrix and fibre respectively. Three specimens each of the prepared composites were tested for tensile and compression strength and at a crosshead speed of 12 mm/min using a Zwick/Roell 1484 Material Testing Machine. The PCUs were not as stiff as their fibre-reinforced composites, which indicate that the stiffness of the PCU composite materials is a function of both the stiffness of the PCU matrix and the interspersed fibres. The tensile moduli of composites of B8 and B9 increased appreciably with PE. An increase of 227% was obtained for the B8 with the incorporation of PE fibres while percentage increase in stiffness for B9 was 148% for PE reinforcement fibres. The compressive modulus dropped with the inclusion of the PE fibres in the B9, a reduction of 55% was recorded while an increment of 4% was obtained with PE added to the B8. The results from this study demonstrate that the tensile and compressive properties of PCU can be custom-tailored to that of the meniscal tissue by systematically embedding reinforcement fibres into the PCU matrix such that a composite with desirable mechanical properties is obtained. The results of both tensile and compressive results visibly revealed the reinforcing effect of the fibres used in this study. However, additional studies are required to completely describe the PCU composite as a candidate meniscal substitute capable of gaining its full functionality

Polymer foams have been used extensively in the testing and development of orthopaedic devices and for verification of computational models. Their use is often preferred over cadaver and animal models due to being relatively inexpensive and their consistent material properties. Successful validation of such models requires accurate material/mechanical data. The assumed range of compressive moduli, provided in the sawbones technical sheet, is 16 MPa to 1.15 GPa depending on the density of foam. In this investigation, we apply two non-contact measurement techniques (digital volume correlation (DVC) and optical surface extensometry) to assess the validity of these reported values. It is thought that such non-contact methods remove mechanical extensometer errors (slippage, misalignment) and restrict the effect of test-machine end-artifacts (friction, non-uniform loading, platen flexibility). This is because measurement is taken directly from the sample, and hence material property assessment should be more accurate. Use of DVC is advantageous as full field strain measurement is possible, however test time and cost is significantly higher than extensometry. Hence, the study also sought to assess the viability of optical extensometry for characterising porous materials. Testing was conducted on five 20 mm cubic samples of 0.32g/cc (20 pcf) solid rigid polyurethane foam (SAWBONES. TM. ). The strain behaviour was characterised by incremental loading via an in situ loading rig. Loading was performed in 0.1 mm increments for 8 load steps with scans between loading steps. Full field strain measurement was performed on one sample by micro focus tomography (muvis centre, Southampton) and subsequent DVC (DaVis, Lavision). Calculation of Young's modulus and Poisson's ratio was then preformed through use of the virtual fields method. These results were subsequently corroborated by use of optical extensometry (MatchID). To account for heterogeneities, axial strain measurements were averaged from six points on the front and rear surfaces. A computationally derived correction factor was then applied to account for through volume strain variations. In each test compressive displacement was applied to 900N (∼2MPa) to remain within the linear elastic region. Significant variability of individual strain measurements were observed from extensometry measurements on the same sample, indicating non-uniform loading did occur in all samples. However by averaging across multiple points linear loading profiles were identified. For all non-contact methods the calculated elastic moduli were found to range between 331–428 MPa whilst the approximated modulus based on cross head displacement was ∼210 MPa. The optical-extensometry gave a considerably higher modulus (p = 0.047) than the DVC results as only surface measurements were made. However, following computational based correction values converged within 6% of one another. Both the DVC and point-tracking results (p = 0.001) indicated substantially higher compressive modulus (137%) than the manufacturer provided properties. This study demonstrates that methods of measuring displacement data on of cellular foams must be carefully considered, as artefacts can lead to significant errors of up to 137%, and such errors may falsely influence the design and validation of tested devices

Summary Statement. Developing titanium (Ti) surfaces that are biocompatible yet serve as deterrents for bacterial attachment and growth are particularly appealing in tackling the ongoing problem of sepsis-induced implant failures. Realising this could include coating Ti with the bioactive lipid, lysophosphatidic acid. Introduction. Surgical revision for failed total joint replacements costs a staggering £300m/yr and approximately 20% of this burden is attributed to implant failure through bacterial infection. Producing biomaterials that deter microbial attachment as well as securing robust osseointegration continues to be a significant research challenge in contemporary bone biomaterials design. Steps to realising novel improvements are further compounded by the concerns raised over resistance of bacteria to many antimicrobial agents. Clearly this is a major constraint necessitating an entirely novel approach to minimising implant infection risk. We therefore turned our attention to certain lysophosphatidic acids (LPAs) for Ti functionalisation. We have found LPA to enhance calcitriol-induced human osteoblast (hOB) maturation. Of further significance is the discovery that LPA can directly inhibit the growth of certain bacteria and even co-operate with some antibiotics to bring about their demise. Herein we describe the fabrication of a hOB-compatible Ti surface with palmitoyl-LPA (P-LPA) which we also find hinders bacterial attachment. Methods. We adopted a self-assembly strategy for the attachment of P-LPA to Ti. Briefly Ti discs (Corin Group, Cirencester, UK) were baked, overnight, at 160°C and then coated with octadecylphosphonic acid (ODP) which has a natural affinity for Ti oxide. Bound ODP provided a tethering point for P-LPA via hydrophobic interaction with the “tail” region perpendicular to the Ti surface. Modified Ti discs were subsequently seeded with hOBs to evaluate their maturation response to calcitriol. In addition modified Ti samples were exposed to either Staphylococcus epidermidis or methicillin-resistant Staphylococcus aureus and the extent of surface coverage determined via crystal violet staining following 24hr incubation. Results. The development of P-LPA functionalised Ti provided a surface that secured hOB maturation in response to calcitriol, as supported by significant increases in total alkaline phosphatase activity, an enzyme expressed in greater abundance as hOBs progress to a more differentiated phenotype. In contrast this Ti substrate was not as attractive to bacteria as evaluated by crystal violet staining and dye recovery from the incubated specimens. Discussion. Multifunctional bone biomaterials that combine host tissue biocompatibility with an antibacterial surface finish will represent the next-generation orthopaedic devices. The biologically active lysophospholipid, LPA, is assuming an emerging interest in hOB biology. This has partly arisen from our discovery that it co-operates with calcitriol to bolster the formation and maturation of hOBs. Another equally exciting property of LPA is the discovery that it can inhibit the growth of bacteria and, in some instances, co-operate with certain antibiotics in killing bacteria. The application of ODP for the attachment of P-LPA to Ti presented itself as a facile step towards developing a novel Ti surface finish. Collectively our preliminary investigations indicate that our modified Ti supports calcitriol-induced hOB maturation but that it deters bacteria

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

Trauma and orthopaedics is the largest of the surgical specialties and yet attracts a disproportionately small fraction of available national and international funding for health research. With the burden of musculoskeletal disease increasing, high-quality research is required to improve the evidence base for orthopaedic practice. Using the current research landscape in the United Kingdom as an example, but also addressing the international perspective, we highlight the issues surrounding poor levels of research funding in trauma and orthopaedics and indicate avenues for improving the impact and success of surgical musculoskeletal research.

Cite this article: Bone Joint J 2014; 96-B:1578–85.