Risk equations for prosthetic joint infections (PJIs) in UK: a retrospective study using the Clinical Practice Research Datalink (CPRD) AURUM and GOLD databases.

BACKGROUND: Prosthetic joint infections (PJIs) are a serious negative outcome of arthroplasty with incidence of about 1%. Risk of PJI could depend on local treatment policies and guidelines; no UK-specific risk scoring is currently available. OBJECTIVE: To determine a risk quantification model for the development of PJI using electronic health records. DESIGN: Records in Clinical Practice Research Datalink (CPRD) GOLD and AURUM of patients undergoing hip or knee arthroplasty between January 2007 and December 2014, with linkage to Hospital Episode Statistics and Office of National Statistics, were obtained. Cohorts' characteristics and risk equations through parametric models were developed and compared between the two databases. Pooled cohort risk equations were determined for the UK population and simplified through stepwise selection. RESULTS: After applying the inclusion/exclusion criteria, 174 905 joints (1021 developed PJI) were identified in CPRD AURUM and 48 419 joints (228 developed PJI) in CPRD GOLD. Patients undergoing hip or knee arthroplasty in both databases exhibited different sociodemographic characteristics and medical/drug history. However, the quantification of the impact of such covariates (coefficients of parametric models fitted to the survival curves) on the risk of PJI between the two cohorts was not statistically significant. The log-normal model fitted to the pooled cohorts after stepwise selection had a C-statistic >0.7. CONCLUSIONS: The risk prediction tool developed here could help prevent PJI through identifying modifiable risk factors pre-surgery and identifying the patients most likely to benefit from close monitoring/preventive actions. As derived from the UK population, such tool will help the National Health Service reduce the impact of PJI on its resources and patient lives.

Poly-beta-amino-ester licofelone conjugates development for osteoarthritis treatment.

Disease-modifying osteoarthritis drugs (DMOADs) are a new therapeutic class for osteoarthritis (OA) prevention or inhibition of the disease development. Unfortunately, none of the DMOADs have been clinically approved due to their poor therapeutic performances in clinical trials. The joint environment has played a role in this process by limiting the amount of drug effectively delivered as well as the time that the drug stays within the joint space. The current study aimed to improve the delivery of the DMOADs into cartilage tissue by increasing uptake and retention time of the DMOADs within the tissue. Licofelone was used a model DMOAD due to its significant therapeutic effect against OA progression as shown in the recent phase III clinical trial. For this purpose licofelone was covalently conjugated to the two different A16 and A87 poly-beta-amino-ester (PBAEs) polymers taking advantage of their hydrolysable, cytocompatible, and cationic nature. We have shown cartilage uptake of the licofelone-PBAE conjugates increased 18 times and retention in tissues was prolonged by 37 times compared to the equivalent dose of the free licofelone. Additionally, these licofelone conjugates showed no detrimental effect on the chondrocyte viability. In conclusion, the cationic A87 and A16 PBAE polymers increased the amount of licofelone within the cartilage, which could potentially enhance the therapeutic effect and pharmacokinetic performance of this drug and other DMOADs clinically.

Nanocomposite orthopaedic bone cement combining long-acting dual antimicrobial drugs.

Antibiotic loaded bone cements are widely used in total joint replacement (TJR); despite many limitations such as a burst release which leads to antibiotic concentration below inhibitory levels and possibly contributing to the selection of antibiotic resistant strains. In order to address such limitations and to simultaneously address antibiotic resistance and short-term antimicrobial activity, we developed a nanocomposite bone cement capable of providing a controlled release of antimicrobial agents from bone cement to act as prophylaxis or treatment against prosthetic joint infections (PJIs). Gentamicin and chlorhexidine were loaded in combination on silica nanoparticles surface using layer-by-layer coating technique (LbL) combining hydrolysable and non-hydrolysable polymers. The drug release from the nanocomposite continued for >50 days at concentrations higher than the commercial formulation containing the same amount of antimicrobial drugs, where burst release for few days were observed. Moreover, the nanocomposite bone cement showed superior antimicrobial inhibition without adversely affecting the mechanical properties or the ability of osteoblasts to grow. In vivo experiments with an infected bone lesion model along with mass-spectrometric analysis also provided further evidence of efficacy and safety of the implanted nanocomposite material as well as its prolonged drug eluting profile. The developed nanocomposite bone cement has the potential to reduce PJIs and enable treatment of resistant established infections; moreover, the newly developed LbL based nano-delivery system may also have wider applications in reducing the threat posed by antimicrobial resistance.

Development, characterization and antimicrobial activity of multilayer silica nanoparticles with chlorhexidine incorporated into dental composites.

OBJECTIVE: In this study a dentistry nanocomposite with prolonged antibacterial activity using silica nanoparticles (SNPs) loaded with chlorhexidine (CHX) was developed. METHODS: SNPs were coated with the Layer-by-Layer technique. Dental composites were prepared with organic matrix of BisGMA/TEGDMA and SNPs with or without CHX (0, 10, 20 or 30% w/w). The physicochemical properties of the developed material were evaluated and agar diffusion method was used to test the antibacterial. In addition, the biofilm inhibitory activity of the composites was evaluated against S. mutans. RESULTS: SNPs were rounded with diameters about 50 nm, the organic load increased with increasing deposited layers. Material samples with SNPs loaded with CHX (CHX-SNPs) showed the highest values of post-gel volumetric shrinkage, that ranged from 0.3% to 0.81%. Samples containing CHX-SNPs 30% w/w showed the highest values of flexural strength and modulus of elasticity. Only samples containing SNPs-CHX showed growth inhibition against S. mutans, S. mitis and S. gordonii in a concentration-dependent manner. The composites with CHX-SNPs reduced the biofilm formation of S. mutans biofilm at 24 h and 72 h. SIGNIFICANCE: The nanoparticle studied acted as fillers and did not interfere with the evaluated physicochemical properties while providing antimicrobial activity against streptococci. Therefore, this initial study is a step forward to the synthesis of experimental composites with improved performance using CHX-SNPs.

A retrospective study of risk factors, causative micro-organisms and healthcare resources consumption associated with prosthetic joint infections (PJI) using the Clinical Practice Research Datalink (CPRD) Aurum database.

BACKGROUND: Prosthetic joint infection (PJI) is a serious complication after joint replacement surgery and it is associated with risk of mortality and morbidity along with high direct costs. METHODS: The Clinical Practice Research Datalink (CPRD) data were utilized to quantify PJI incidence after hip or knee replacement up to 5 years after implant and a variety of risk factors related to patient characteristics, medical and treatment history along with characteristics of the original surgery were analyzed through Cox proportional hazard. RESULTS: 221,826 patients (individual joints 283,789) met all the inclusion and exclusion criteria of the study; during the study follow-up period (5 years), 707 and 695 PJIs were diagnosed in hip and knee, respectively. Patients undergoing joint replacement surgery during an unscheduled hospitalization had greater risk of PJI than patients whose surgery was elective; similarly, the risk of developing PJI after a secondary hip or knee replacement was about 4 times greater than after primary arthroplasty when adjusted for all other variables considered. A previous diagnosis of PJI, even in a different joint, increased the risk of a further PJI. Distribution of average LoS per each hospitalization caused by PJI exhibited a right skewed profile with median duration [IQR] duration of 16 days [8-32] and 13 days [7.25-32] for hip and knee, respectively. PJIs causative micro-organisms were dependent on the time between initial surgery and infection offset; early PJI were more likely to be multispecies than later (years after surgery); the identification of Gram- pathogens decreased with increasing post-surgery follow-up. CONCLUSIONS: This study offers a contemporary assessment of the budgetary and capacity (number and duration of hospitalizations along with the number of Accident and Emergency (A&E) visits) posed by PJIs in UK for the national healthcare system (NHS). The results to provide risk management and planning tools to health providers and policy makers in order to fully assess technologies aimed at controlling and preventing PJI. The findings add to the existing evidence-based knowledge surrounding the epidemiology and burden of PJI by quantifying patterns of PJI in patients with a relatively broad set of prevalent comorbidities.

Low-Field Actuating Magnetic Elastomer Membranes Characterized using Fibre-Optic Interferometry.

Smart robotic devices remotely powered by magnetic field have emerged as versatile tools for wide biomedical applications. Soft magnetic elastomer (ME) composite membranes with high flexibility and responsiveness are frequently incorporated to enable local actuation for wireless sensing or cargo delivery. However, the fabrication of thin ME membranes with good control in geometry and uniformity remains challenging, as well as the optimization of their actuating performances under low fields (milli-Tesla). In this work, the development of ME membranes comprising of low-cost magnetic powder and highly soft elastomer through a simple template-assisted doctor blading approach, is reported. The fabricated ME membranes are controllable in size (up to centimetre-scale), thickness (tens of microns) and high particle loading (up to 70 wt.%). Conflicting trade-off effects of particle concentration upon magnetic responsiveness and mechanical stiffness are investigated and found to be balanced off as it exceeds 60 wt.%. A highly sensitive fibre-optic interferometric sensing system and a customized fibre-ferrule-membrane probe are first proposed to enable dynamic actuation and real-time displacement characterization. Free-standing ME membranes are magnetically excited under low field down to 2 mT, and optically monitored with nanometer accuracy. The fast and consistent responses of ME membranes showcase their promising biomedical applications in nanoscale actuation and sensing.

Feasibility and application of machine learning enabled fast screening of poly-beta-amino-esters for cartilage therapies.

Despite the large prevalence of diseases affecting cartilage (e.g. knee osteoarthritis affecting 16% of population globally), no curative treatments are available because of the limited capacity of drugs to localise in such tissue caused by low vascularisation and electrostatic repulsion. While an effective delivery system is sought, the only option is using high drug doses that can lead to systemic side effects. We introduced poly-beta-amino-esters (PBAEs) to effectively deliver drugs into cartilage tissues. PBAEs are copolymer of amines and di-acrylates further end-capped with other amine; therefore encompassing a very large research space for the identification of optimal candidates. In order to accelerate the screening of all possible PBAEs, the results of a small pool of polymers (n = 90) were used to train a variety of machine learning (ML) methods using only polymers properties available in public libraries or estimated from the chemical structure. Bagged multivariate adaptive regression splines (MARS) returned the best predictive performance and was used on the remaining (n = 3915) possible PBAEs resulting in the recognition of pivotal features; a further round of screening was carried out on PBAEs (n = 150) with small variations of structure of the main candidates from the first round. The refinements of such characteristics enabled the identification of a leading candidate predicted to improve drug uptake > 20 folds over conventional clinical treatment; this uptake improvement was also experimentally confirmed. This work highlights the potential of ML to accelerate biomaterials development by efficiently extracting information from a limited experimental dataset thus allowing patients to benefit earlier from a new technology and at a lower price. Such roadmap could also be applied for other drug/materials development where optimisation would normally be approached through combinatorial chemistry.

PMMA bone cement containing long releasing silica-based chlorhexidine nanocarriers.

Prosthetic joint infections (PJI) are still an extremely concerning eventuality after joint replacement surgery; growing antibiotic resistance is also limiting the prophylactic and treatment options. Chlorhexidine (a widely used topical non-antibiotic antimicrobial compound) coatings on silica nanoparticles capable of prolonged drug release have been successfully developed and characterised. Such nanocarriers were incorporated into commercial formulation PMMA bone cement (Cemex), without adversely affecting the mechanical performance. Moreover, the bone cement containing the developed nanocarriers showed superior antimicrobial activity against different bacterial species encountered in PJI, including clinical isolates already resistant to gentamicin. Cytocompatibility tests also showed non inferior performance of the bone cements containing chlorhexidine releasing silica nanocarriers to the equivalent commercial formulation.

Poly beta amino ester coated emulsions of NSAIDs for cartilage treatment.

Delivering drugs directly into cartilage is still the major challenge in the management and treatment of osteoarthritis (OA) resulting from the aneural, avascular and alymphatic nature of an articular cartilage structure. Progress has been made in the design of drug delivery systems that enhance corticosteroid uptake and retention in cartilage; however also non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for patients affected by OA and a drug delivery system specifically designed for this drug category is currently unavailable. We developed an approach based on the preparation of NSAID oil-in-water emulsions coated with poly-beta-amino-esters (PBAEs) to exploit the cartilage penetrating ability of such polymers and the high solubility of drugs in oil. These emulsions containing different NSAIDs (indomethacin, ketorolac, diclofenac and naproxen) exhibited enhanced and prolonged drug localisation not only in healthy cartilage tissues but also in early-stage OA samples. The critical role of the PBAE layer on oil droplets was established along with the retained biological activity of the drug as glycosaminoglycan (GAG) and collagen degradation induced by interleukin-1 (IL-1) was prevented by the novel technology. Oil-in-water coated emulsions are very flexible and cost-effective drug delivery systems and such an approach presented here could provide a substantial improvement in the therapeutic treatments of OA and thus patients' outcomes.

Amplify antimicrobial photo dynamic therapy efficacy with poly-beta-amino esters (PBAEs).

Light-activated antimicrobial agents (photosensitisers) are promising alternatives to antibiotics for the treatment of skin infections and wounds through antimicrobial photo dynamic therapy (aPDT); utilisation of this technique is still restricted by general low efficacy requiring long exposure time (in the order of tens of minutes) that make the treatment very resource intensive. We report for the first time the possibility of harvesting the cell penetrating properties of poly-beta-amino esters (PBAEs) in combination with toluidine blue O (TBO) to shorten aPDT exposure time. Candidates capable of inactivation rates 30 times quicker than pure TBO were discovered and further improvements through PBAE backbone optimisation could be foreseen. Efficacy of the complexes was PBAE-dependent on a combination of TBO uptake and a newly discovered and unexpected role of PBAEs on reactive species production. Chemometric approach of partial least square regression was employed to assess the critical PBAE properties involved in this newly observed phenomenon in order to elicit a possible mechanism. The superior antimicrobial performance of this new approach benefits from the use of well established, low-cost and safe dye (TBO) coupled with inexpensive, widely tested and biodegradable polymers also known to be safe. Moreover, no adverse cytotoxic effects of the PBAEs adjuvated TBO delivery have been observed on a skin cells in vitro model demonstrating the safety profile of this new technology.

Rheometer enabled study of cartilage frequency-dependent properties.

Despite the well-established dependence of cartilage mechanical properties on the frequency of the applied load, most research in the field is carried out in either load-free or constant load conditions because of the complexity of the equipment required for the determination of time-dependent properties. These simpler analyses provide a limited representation of cartilage properties thus greatly reducing the impact of the information gathered hindering the understanding of the mechanisms involved in this tissue replacement, development and pathology. More complex techniques could represent better investigative methods, but their uptake in cartilage research is limited by the highly specialised training required and cost of the equipment. There is, therefore, a clear need for alternative experimental approaches to cartilage testing to be deployed in research and clinical settings using more user-friendly and financial accessible devices. Frequency dependent material properties can be determined through rheometry that is an easy to use requiring a relatively inexpensive device; we present how a commercial rheometer can be adapted to determine the viscoelastic properties of articular cartilage. Frequency-sweep tests were run at various applied normal loads on immature, mature and trypsinased (as model of osteoarthritis) cartilage samples to determine the dynamic shear moduli (G*, G' G″) of the tissues. Moduli increased with increasing frequency and applied load; mature cartilage had generally the highest moduli and GAG depleted samples the lowest. Hydraulic permeability (KH) was estimated from the rheological data and decreased with applied load; GAG depleted cartilage exhibited higher hydraulic permeability than either immature or mature tissues. The rheometer-based methodology developed was validated by the close comparison of the rheometer-obtained cartilage characteristics (G*, G', G″, KH) with results obtained with more complex testing techniques available in literature. Rheometry is relatively simpler and does not require highly capital intensive machinery and staff training is more accessible; thus the use of a rheometer would represent a cost-effective approach for the determination of frequency-dependent properties of cartilage for more comprehensive and impactful results for both healthcare professional and R&D.

Polymer colloids as drug delivery systems for the treatment of arthritis.

The most common types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA) which are themain causes of disability and pain among older people. Current treatment of arthritis mainly consists of oral and intra-articular medications. Despite the efficacy of the intraarticular injections over the oral treatment, it is still limited by the rapid clearance of the injected drug. Therefore, a rational design of drug delivery systems (DDSs) able to delivery drugs in controlled manner and for required period of time to the arthritis joint is a key in developing safe and effective formulations for OA and RA. In this paper various colloidal systems like nanoparticles, liposomes, cationic carriers, hydrogels, and emulsion-based carriers were presented and discussed in light of their use and efficacy as delivery systems to transport therapeutics for arthritis treatment. Factors influencing the delivery efficacy such as size, charge, structure, drug uptake, retention and its release profile alongside with cytocompatibility and safety were addressed. Moreover, the advantages and disadvantages of the different colloidal systems were emphasised.

Long acting anti-infection constructs on titanium.

Peri-prosthetic joint infections (PJI) are a serious adverse event following joint replacement surgeries; antibiotics are usually added to bone cement to prevent infection offset. For uncemented prosthesis, alternative antimicrobial approaches are necessary in order to prevent PJI; however, despite elution of drug from the surface of the device being shown one of the most promising approach, no effective antimicrobial eluting uncemented device is currently available on the market. Consequently, there is a clinical need for non-antibiotic antimicrobial uncemented prosthesis as these devices present numerous benefits, particularly for young patients, over cemented artificial joints. Moreover, non-antibiotic approaches are driven by the need to address the growing threat posed by antibiotic resistance. We developed a multilayers functional coating on titanium surfaces releasing chlorhexidine, a well-known antimicrobial agent used in mouthwash products and antiseptic creams, embedding the drug between alginate and poly-beta-amino-esters. Chlorhexidine release was sustained for almost 2 months and the material efficacy and safety was proven both in vitro and in vivo. The coatings did not negatively impact osteoblast and fibroblast cells growth and were capable of reducing bacterial load and accelerating wound healing in an excisional wound model. As PJI can develop weeks and months after the initial surgery, these materials could provide a viable solution to prevent infections after arthroplasty in uncemented prosthetic devices and, simultaneously, help the fight against antibiotic resistance.

Optimisation and feature selection of poly-beta-amino-ester as a drug delivery system for cartilage.

Drug localisation is still one of the main challenges in treating pathologies affecting cartilage; poly-beta-amino-esters (PBAEs) drug conjugates are a possible solution; however, their efficacy highly depends on the polymer structure hence the full potential of this delivery system is still unknown. For the purpose of optimising the delivery system design, a large library of PBAEs was synthesised and dexamethasone (DEX) uptake in cartilage was determined. All three components of PBAE (amine, acrylate and end-capping) impacted the outcome. The most effective PBAE identified enhanced DEX uptake by 8 folds compared to an equivalent dose of the commercial formulation and also prevented, through delivery of DEX, the cartilage degradation caused by IL-1α (interleukine1α). A chemometrics based predictive model was constructed and PBAEs properties most affecting the performance of the drug delivery systems were identified. This model will allow further computer based PBAEs optimisation and fast track the bench to market process for this delivery system.

Systematic Review and Meta-Analysis of Tobacco Use as a Risk Factor for Prosthetic Joint Infection After Total Hip Replacement.

BACKGROUND: A prosthetic joint infection (PJI) is one of the possible complications after total hip arthroplasty (THA). Several studies, but not all, have reported smoking as a risk factor of PJIs in orthopaedic surgery. This study summarizes the most recent evidence using a systematic review of whether tobacco use (not only tobacco smoking) is a risk factor in developing PJIs, specifically after THA. METHODS: Ovid Medline, EMBASE, Scopus, Web of Science, and Cochrane databases were searched from inception to July 2019 to identify case-control studies that examined the PJI risk in tobacco users and tobacco nonusers undergoing THA. Publication bias was also assessed through funnel plots. RESULTS: Searches identified 2689 articles, and 10 of these, involving a total of 20,640 patients, met the inclusion criteria. The overall odds ratio (pooled odds ratio) to develop either a superficial infection, a deep infection, or an infection requiring revision surgery for tobacco users vs nonusers was 1.54 (95% confidence interval: 1.25-1.91) when a fixed-effect model was used and 1.56 (95% confidence interval: 1.10-2.21) when a random-effect model was used. No publication bias was observed among the identified studies. CONCLUSIONS: The findings of the study indicated that tobacco use is associated with a higher risk of PJIs in patients undergoing THA.

Nanoparticle-based model of anti-inflammatory drug releasing LbL coatings for uncemented prosthesis aseptic loosening prevention.

INTRODUCTION: The only treatment for aseptic loosening is the replacement of the prosthesis through revision surgery. A preventive approach, achieved through anti-inflammatory drugs released from the device, has shown to be a viable strategy; however, the performance of these devices is not yet satisfactory thus further improvements are necessary. METHODS: We used titanium nanoparticles as a model for implant surfaces and developed a coating containing dexamethasone (DEX) using layer-by-layer deposition. RESULTS: The amount of deposited drug depended on the number of layers and the release was sustained for months. The efficiency of the released DEX in reducing inflammation markers (tumor necrosis factor alpha and IL-6) produced by human monocytes and macrophages was similar to the pure drug at the same concentration without negative impacts on the viability and morphology of these cells. CONCLUSION: These coatings were not inferior to medical grade titanium (the standard material used in uncemented devices) regarding their ability to sustain osteoblasts and fibroblasts growth.

Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis.

BACKGROUND: Aseptic loosening, as a consequence of an extended inflammatory reaction induced by wear particles, has been classified as one of the most common complications of total joint replacement (TJR). Despite its high incidence, no therapeutical approach has yet been found to prevent aseptic loosening, leaving revision as only effective treatment. The local delivery of anti-inflammatory drugs to modulate wear-induced inflammation has been regarded as a potential therapeutical approach to prevent aseptic-loosening. METHODS: In this context, we developed and characterized anti-inflammatory drug-eluting TiO2 surfaces, using nanoparticles as a model for larger surfaces. The eluting surfaces were obtained by conjugating dexamethasone to carboxyl-functionalized TiO2 particles, obtained by using either silane agents with amino or mercapto moieties. RESULTS: Zeta potential measurements, thermogravimetric analysis (TGA) and drug release results suggest that dexamethasone was successfully loaded onto the TiO2 particles. Release was pH dependent and greater amounts of drug were observed from amino route functionalized surfaces. The model-system was then tested for its cytotoxic and anti-inflammatory properties in LPS-stimulated macrophages. Dexamethasone released from amino route functionalized surfaces TiO2 particles was able to decrease LPS-induced nitric oxide (NO) and TNF-a production similarly to pure DEX at the same concentration; DEX released from mercapto route functionalized surfaces was at a too low concentration to be effective. CONCLUSION: Dexamethasone released from amino functionalized titanium can offer the possibility of preventing asepting loosening of joint replacement devices.

Prolonged Antimicrobial Activity of PMMA Bone Cement with Embedded Gentamicin-Releasing Silica Nanocarriers.

Antibiotic laden bone cements are regularly employed to prevent infections after joint replacement surgeries. We have developed silica nanocarriers loaded with gentamicin as a drug delivery system to be dispersed in poly methyl-methacrylate (PMMA) bone cement for controlling and extending the release of the antibiotic from bone cements, thus proving a prolonged antimicrobial activity. Layer-by-layer self-assembly was used to deposit gentamicin between alginate layers and two different poly ß-amino esters on the silica nanoparticles. The release of gentamicin from PMMA bone cement containing silica nanocarriers continued for about 30 days compared to 6 days when the same amount of antibiotic was added as a pure powder (as in commercial formulations); moreover, the medium containing the released antimicrobial drug was capable of preventing the growth of numerous bacteria species responsible for prosthetic joint infections (both catalogue strains and clinical isolates) for longer periods of time than in the case of commercial formulations, thus confirming the extended antimicrobial properties of the drug once released from the carrier. No detrimental effects toward human osteoblasts were also observed; moreover, bone cement material characteristics such as curing time, water uptake, and mechanical properties were unaffected when the silica nanocarriers were added.

LbL-assembled gentamicin delivery system for PMMA bone cements to prolong antimicrobial activity.

INTRODUCTION: Antibiotic-loaded poly(methyl methacrylate) bone cements (ALBCs) are widely used in total joint replacement (TJR), for local delivery of antibiotics to provide prophylaxis against prosthetic joint infections (PJI). One of the shortcomings of the current generation of ALBCs is that the antibiotic release profile is characterized by a burst over the first few hours followed by a sharp decrease in rate for the following several days (often below minimum inhibitory concentration (MIC)), and, finally, exhaustion (after, typically, ~ 20 d). This profile means that the ALBCs provide only short-term antimicrobial action against bacterial strains involved PJI. RATIONALE: The purpose of the present study was to develop an improved antibiotic delivery system for an ALBC. This system involved using a layer-by-layer technique to load the antibiotic (gentamicin sulphate) (GEN) on silica nanoparticles, which are then blended with the powder of the cement. Then, the powder was mixed with the liquid of the cement (NP-GEN cement). For controls, two GEN-loaded brands were used (Cemex Genta and Palacos R+G). Gentamicin release and a host of other relevant properties were determined for all the cements studied. RESULTS: Compared to control cement specimens, improved GEN release, longer antimicrobial activity (against clinically-relevant bacterial strains), and comparable setting time, cytocompatibility, compressive strength (both prior to and after aging in PBS at 37 oC for 30 d), 4-point bend strength and modulus, fracture toughness, and PBS uptake. CONCLUSIONS: NP-GEN cement may have a role in preventing or treating PJI.