Thermal damage to bone related to the exothermic polymerisation of bone cement (PMMA) remains a concern. A series of studies were conducted to examine PMMA bone interface during cemented arthroplasty. In vitro and in vivo temperature distributions were performed in the laboratory and human and animal surgery. In vivo (10 patients) measurements of cement temperature during cementing of BHR femoral prosthesis using thermocouples. Intra-operative measurement of cement temperature in BHR in the presence of femoral head cysts was examined in patients. The BHR femoral heads were sectioned to assess cement mantle as well as position of thermocouples. An additional study was performed in sheep with PMMA implanted into cancellous defects. Thermocouples were used to monitor temperature in the cement as well as adjacent bone. Histology and CT was used to assess any thermal damage. The exothermic reaction of PMMA during polymerization does indeed result in an increase in temperature at the interface with bone. The in vivo study recorded a maximum temperature of 49.12C for approximately three minutes in the cancellous bone underneath the BHR prosthesis. This exposure is probably not sufficient to cause significant injury to the femoral head. The maximum temperature of the cement on the surface of the bone was 54.12C, whereas the maximum recorded in the cement in the mixing bowl was 110.2C. In the presence of artificial cysts within the bone, however, temperatures generated within the larger cysts, and even at the bone-cement interface of these cysts, reached levels greater than those previously shown to be harmful to bone. This occurred in one case even in the 1 cc cyst. Routine histology revealed a fibrous layer at the cement bone interface in the sheep study. Fluorescent microscopy demonstrated bone label uptake adjacent to the defect site. Histology did not reveal thermal necrosis in the defects in terms of bony necrosis. CT data was used to measure the amount of PMMA placed into each defect. This analysis revealed a range of volumes that did not seem to influence the histology. The heat of cement polymerisation in resurfacing as performed in our study is not sufficient to cause necrosis. This may reflect the ability of the body to rapidly conduct heat away by acting as a heat sink. The temperature-conducting properties of the metal prosthesis are also likely to be important

Introduction. Temporary use of antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement spacers in two-stage revisions is considered to be standard of care for patients with a chronic infection of a joint replacement. Spacers should be wear resistant and load-bearing to avoid prolonged immobilisation of the patient and to reduce morbidity. Most cement spacers contain barium sulphate or zirconium dioxide as radio-opaque substrate. Both are quite hard materials that may negatively influence the wear behaviour of the spacer. Calcium carbonate is another radio-opaque substrate with lower hardness potentially increasing the wear resistance of the spacer materials. The purpose of the study was to compare a prototype PMMA knee spacer (calcium carbonate loaded) with a commercially available spacer (containing barium sulphate) regarding the wear performance and particle release in a knee wear simulator. Material and Methods. Spacer K (TECRES, Italy) was used as barium sulphate (10%) containing spacer material. A prototype material (Heraeaus Medical, Germany) with 15% calcium carbonate was compared. Both were gentamicin impregnated, ready-made for clinical application (preformed) and consist of a tibial and a femoral component. Force-controlled simulation was carried out on an AMTI knee simulator. The test parameters were in accordance to ISO 14243–1 with a 50% reduced axial force (partial weight bearing). Tests were carried out at 37 °C in closed chambers filled with calf serum. Tests were run for 500,000 cycles at a frequency of 1 Hz. For wear analysis, gravimetric wear measurements according to ISO 14243–2 and wear particle analysis according to ASTM F1877–05 were performed. Results. Fig. 1 presents the results of the gravimetric wear measurements. For the Spacer K cement a mean articular wear mass of 375.53±161.22 mg was determined after 500.000 cycles (femoral components: 149.55±17.30 mg, tibial components: 225.98±153.01 mg). The prototype cement showed lower mean total wear of 136.32±37.58 mg (femoral components: 74.32±33.83 mg, tibial components: 61.99±15.74 mg). However, a statistically significant lower wear rate was only seen for the femoral components (p=0,027). In Fig. 2 isolated PMMA wear particles are shown and the morphological characteristics are given in Tab. 1. Discussion and conclusion. The prototype material showed better wear performance in terms of gravimetric wear and particle release. Thus calcium carbonate seems to be a promising material as radio-opaque substrate in PMMA spacers. Nevertheless, the wear amount released from both spacer materials is much higher as compared to conventional total knee replacements with polyethylene inserts. In this context biological reactions against PMMA particles and an increased release of cytokines have been reported in vitro [1] and furthermore, the promotion of osteolysis has been shown in vivo in the presence of PMMA particles [2]. As a clinical consequence we suggest excessive debridement during removal of the cement spacer components to reduce the risk of third body wear for the final joint replacement. Beside the wear performance further studies are essential to prove the mechanical stability and the antibiotic release kinetics for the prototype cement

Introduction. Antibiotic loaded polymethyle methacrylate spacers are commonly used in the management of septic hip replacements. Aim. The aim of this study was to determine wear patterns on the articulating surfaces of these spacers, as well as to determine the extent of PMMA particulate debris generation. Method. We took tissue specimens around the acetabulae in 12 cases at the time of the second stage procedure for septic total hip revisions. These were subjected to histological analysis to determine the extent of PMMA particulate debris contamination. We also performed a basic explant retrieval analysis of the articulating surfaces of the PMMA spacers to determine any specific wear patterns. Results. We found numerous PMMA particles in the acetabular soft tissues biopsied. The particle concentration was highest in the area of the acetabular fovea. We could also demonstrate specific wear patterns on the spacers that could be correlated with the generally mismatched articulating couple between the spacer and the bony acetabulum. We could also demonstrate some boney destruction present in the acetabulum with long-term spacer use. Conclusions. We concluded that significant amounts of PMMA particulate debris are generated by these articulating antibiotic spacers. The total volume of this debris may be determined by specific wear patterns on the spacers’ surfaces. We recommend a thorough debridement to decrease the PMMA particle load generated. Consideration in respect of the bearing surface implanted after the explantation of the PMMA spacer should take into account the effect of the debris on the bearing surfaces. We also make recommendations in respect of the design of these PMMA spacers

Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in. sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use

Great strides have been made in the early detection and treatment of cancer which is resulting in improved survivability and more Canadians living with cancer. Approximately 80% of primary breast, lung, and prostate cancers metastasize to the spine. Poly-methyl methacrylate (PMMA) bone cement is one of the most commonly used bone substitutes in spine surgery. In clinical practice it can be loaded with various drugs, such as antibiotics or chemotheraputic drugs, as a means of local drug delivery. However, studies have shown that drugs loaded into PMMA cement tend to release in small bursts in the first 48–72 hours, and the remaining drug is trapped without any significant release over time. The objective of this study is to develop a nanoparticle-functionalized PMMA cement for use as a sustained doxorubicin delivery device. We hypothesize that PMMA cement containing mesoporous silica nanoparticles will release more doxorubicin than regular PMMA. High viscosity SmartSet ™ PMMA cement by DePuy Synthes was used in this study. The experimental group consisted of 3 replicates each containing 0.24 g of mesoporous silica nanoparticles, 1.76 g of cement powder, 1ml of liquid cement monomer and 1 mg of doxorubicin. The control group consisted 3 replicates each containing 2.0 g of cement powder, 1ml of liquid cement monomer and 1 mg of doxorubicin. The experimental group contained an average of 8.18 ± 0.008 % (W/W) mesoporous silica nanoparticles. Each replicate was casted into a cylindrical block and incubated in a PBS solution which was changed at predetermined intervals for 45 days. The concentration of eluted doxorubicin in each solution was measured using a florescent plate reader. The mechanical properties of cement were assessed by unconfined compression testing. The effect of the doxorubicin released from cement on prostate and breast tumor cell metabolic activity was assessed using the Alamar Blue test. After 45 days the experimental group released 3.24 ± 0.25 % of the initially loaded doxorubicin which was more than the 2.12 ± 0.005% released by the control group (p 0.03). There was no statistically significant difference in Young's elasticity modulus between groups (p 0.53). Nanoparticle functionalized PMMA suppressed the metabolic activity of prostate cancer by more than 50 percent but did not reach statistical significance. Nanoparticle functionalized PMMA suppressed the metabolic activity of breast cancer cells by 69 % (p < 0.05). Nanoparticle-functionalized PMMA cement can release up to 1.53 times more doxorubicin than the standard PMMA. The use of mesoporous silica nanoparticles to improve drug release from PMMA cement shows promise. In the future, in vivo experiments are required to test the efficacy of released doxorubicin on tumor cell growth

Aim. The preparation of antibiotic-containing polymethyl methacrylate (PMMA), as spacers generates a high polymerization heat, which may affect their antibiotic activity; it is desirable to use bone cement with a low polymerization heat. Calcium phosphate cement (CPC) does not generate heat on polymerization, and comparative elution testings are reported that vancomycin (VCM)-containing CPC (VCM-CPC) exceeded the antibiotic elution volume and period of PMMA (VCM-PMMA). Although CPC alone is a weak of mechanical property spacer, the double-layered, PMMA-covered CPC spacer has been created and clinically used in our hospital. In this study, we prepared the double-layered spacers: CPC covered with PMMA and we evaluated its elution concentration, antimicrobial activity and antibacterial capability. Method. We prepared spherical, double-layered, PMMA-coated (CPC+PMMA; 24 g CPC coated with 16 g PMMA and 2 g VCM) and PMMA alone (40 g PMMA with 2 g VCM) spacers (5 each). In order to facilitate VCM elution from the central CPC, we drilled multiple holes into the CPC from the spacer surface. Each spacer was immersed in phosphate buffer (1.5 mL/g of the spacer), and the solvent was changed daily. VCM concentrations were measured on days 1, 3, 7, 14, 28, 56, and 84. Antimicrobial activity against MRSA and MSSA was evaluated by the broth microdilution method. After measuring all the concentration, the spacers were compressed at 5 mm/min and the maximum compressive load up to destruction was measured. Results. The VCM concentration of the CPC+PMMA spacer exceeded that of the PMMA spacer at all-time points; in particular, it was approximately 7.3 times (109.30 vs. 15.03 μg/mL) and approximately 9.1 times (54.47 vs. 6.50 μg/mL) greater on days 14 and 28, respectively. Using the broth microdilution method, we found that the CPC+PMMA spacer had higher antimicrobial activity than the PMMA model. On day 56, the PMMA spacer lost the capability to inhibit bacterial growth, but the CPC+PMMA spacer maintained this ability. The average maximum compressive load for the CPC+PMMA was 7.28 kN, and that of PMMA was 16.21 kN. Conclusions. The CPC+PMMA spacer was superior to PMMA alone in VCM elution volume and duration, so CP- C+PMMA may be effective for the treatment of MRSA and MSSA infection. The double-layered, antibiotic-loaded cement spacer may maintain antibacterial capability and sufficient strength

Aim. We aimed to compare the in vitro antibacterial activity of Bioactive Glass (BAG) S53P4, which is a compound showing local antibacterial activity, to that of antibiotic-loaded polymethylmethacrylate (PMMA) against multidrug resistant bacteria from osteomyelitis (OM) and prosthetic joint infection (PJI) isolates. Method. We studied convenience samples of multidrug resistant (MDR) microorganisms obtained from patients presenting OM and prosthetic joint infection (PJI). Mixtures containing tryptic soy broth (TSB) and inert glass beads (2mm), BAG-S53P4 granules (0.5–0.8mm and <45 mm) and Gentamicin or Vancomycin-loaded PMMA beads were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MR-CoNS), Pseudomonas aeruginosa or Klebsiella pneumoniae isolates. Glass beads (2.0mm) were used as a control. Antibacterial activity was evaluated by means of time-kill curve, through seeding the strains on blood agar plates, and subsequently performing colony counts after 24, 48, 72, 96, 120 and 168 hours of incubation. Differences between groups were evaluated by means of two-way analysis of variance (ANOVA) and Bonferroni's t test. Results. Inhibition of bacterial growth started soon after 48 hours of incubation, reached zero CFU/ml between 120 and 168 hours of incubation for both antibiotic-loaded PMMA and BAG S53P4 groups, in comparison with inert glass (p< 0.05). No difference regarding time-kill curves between antibiotic-loaded PMMA and BAG S53P4 was observed. Moreover, despite no difference was observed between both Vancomycin - or Gentamicin-loaded PMMA and BAG groups, there was statistical difference between the effectiveness of all treatments (BAG included) against gram-positive cocci and gram-negative bacilli, the latter of which requiring longer time frames for the cultures to yield no bacterial growth. Conclusions. BAG S53P4 presented antibacterial properties as much as antibiotic-loaded PMMA for MDR bacteria producing OM and PJI, although presenting differences between its effectiveness against different bacterial groups

Introduction. The management of open long bone fractures is well described and has been standardised through a number of well-established guidelines. However, there is no consensus regarding the application of local antibiotics into the open fracture site as a means of reducing infection rates. Materials & Methods. A systematic review and meta-analysis were undertaken as per PRISMA guidelines. PROSPERO Registration CRD42022323545. PubMed, EMBASE, Scopus and CENTRAL were the databases assessed. The Newcastle Ottawa Scale and the Rob 2 Tool were used to assess bias. A qualitative synthesis of all included studies and meta-analysis of suitable subgroups was undertaken. Results. In total, 12 studies (11 observational, 1 RCT) assessing 2431 open fractures were included for analysis. All compared the addition of a local antibiotic therapy to a standard treatment versus the standard treatment alone. The methods of delivery were vancomycin powder (4 papers), tobramycin polymethylmethacrylate beads (4 papers), gentamicin coated intramedullary (IM) nails (2 papers), gentamicin injections (1 paper) and antibiotic released IM core cement (1 paper). The addition of vancomycin powder did not decrease infection rates in comparison to intravenous antibiotics alone (OR 1.3, 95% CI (0.75 – 2.26)). Antibiotic coated IM Nails appear to have an association with lower infection rates than standard IM Nails. PMMA antibiotics have shown varied results in reducing infection rates depending on the individual studies. Conclusions. There are numerous methods available to deliver antibiotics locally to an open fracture site. Further high-quality research is required to provide a definitive conclusion on their efficacy irrespective of delivery method

The burden of periprosthetic joint infection (PJI) continues to rise and the management of this dreaded complication continues to pose challenges to the orthopaedic community. Dr Buchholz from the Endo Klinik has been credited for reporting the initial observation that addition of antibiotic to polymethylmethacrylate (PMMA) cement lead to better ability to deliver higher concentrations of antibiotic to the joint milieu and avoid administration of high doses of systemic antibiotics with potential for systemic toxicity. Addition of antibiotics to PMMA cement has continued to be an important aspect of managing patients with chronic PJI. The rationale for this practice is that higher doses of local antibiotics can be reached without placing the patients at risk of systemic toxicity. Whether a one-stage or a two-stage exchange arthroplasty is being performed, antibiotics that can withstand the exothermic reaction of PMMA and are able to elude from cement are added at various doses to the PMMA for later delivery. Although this practice continues to be almost universal, there are a few unknowns. First of all, a recent study raised a valid question regarding this practice. Though intuitively logical, addition of antibiotics to PMMA spacers has not been scrutinised by any level 1 study and hence one is not able to prove that this practice does indeed accomplish its intended objectives of reducing recurrence or persistence of infection. Orthopaedic community is advised to seek avenues to generate this much-needed evidence. The other main unknown is how much, and in some instances which antibiotic, needs to be added to the PMMA cement. Some authorities have declared that antibiotics can be added at high doses, with an average total dose of 10.5 g of vancomycin (range, 3–16 g) and 12.5 g of gentamicin (range, 3.6–19.2 g) in one study, to PMMA cement without the fear of systemic toxicity. In recent years, renal toxicity and other systemic adverse effects have been attributed to addition of high doses of antibiotics to cement. I have personally witnessed such adverse reactions in a few patients. Although initially I was inclined to “blame” the concurrent administration of systemic antibiotics for the renal toxicity that patients developed following insertion of spacer, selective nephrotoxicity (i.e. reaction to aminoglycoside that was only present in the spacer and not systemically administered) and resolution of the nephrotoxicity upon removal of antibiotic spacer, convinced me that our nephrology colleagues have a valid reason to be concerned about addition of high doses of antibiotics to PMMA spacers. What has become clear is that high viscosity cements containing MA-MMA copolymers have been shown to have better antibiotic elution profiles than other PMMA formulations. So when fashioning a spacer in the operating room the surgeon needs to be aware of the differences in elution profile of antibiotics from PMMA and individualise the dose of antibiotics being added to spacer based on the type and viscosity of cement being used and the renal status of the patient. Thus, systemic toxicity caused by addition of antibiotics to cement spacer appears to be a real issue in some circumstances and this needs to be born in mind when managing patients with PJI. There are numerous other issues related to the use of antibiotic cement spacers. In the hip, the lack of adequate offset and limited portfolio of products result in laxity in the soft tissue and subsequent dislocation of the hip. In addition, the dose and type of antibiotic in the premanufactured spacers, at least in the US, are inadequate to lead to a substantial delivery of antibiotics in the local tissues. Because of these issues, I prefer to fabricate “customised” spacers for each patient that I operate on

Multiple studies have established an inverse relationship between ambient theatre temperatures and polymethyl methacrylate (PMMA) cement setting times. It is also known that allowing cement to equilibrate to ambient theatre temperatures restores expected setting characteristics. One overlooked entity is the transport and storage conditions of cement. This is important in tropical regions, where extreme temperature and humidity may cause rapid cement setting times, resulting in potentially significant intra-operative complications. This study investigated the relationship between extreme transport and storage conditions of Antibiotic Simplex cement (Stryker), and the effect on setting times at Cairns Hospital, Far North Queensland, Australia. Fifty units of cement were divided evenly into a control arm and four experimental arms. The experimental arms were designed to mimic potential transport and storage conditions. They included seven days of storage in a medication fridge, on the hospital loading dock, in a cane shed, and in a Toyota Landcruiser parked outdoors during January 2022. Humidity and temperature readings were recorded. The samples in each group were evenly distributed to equilibrate to theatre conditions for 1 hour and 24 hours. Setting time was recorded when a no. 15 scalpel blade was unable to mark the surface. All three ‘hot’ exposures setting times were significantly faster for both 1 hour (ρ=0.001) and 24 hours (ρ=0.024) equilibration times. The difference in setting times for the ‘cold’ exposure was not significant for either equilibration times (ρ=1). To our knowledge, this is the first study investigating cement setting times in tropical climates. Further studies are required to address the effect of these conditions on biomechanical strength of PMMA cement. We conclude that extreme heat and humidity during transport and storage have a statistically significant effect on cement setting times

Objectives. Investigate the incorporation of an antibiotic in bone cement using liposomes (a drug delivery system) with the potential to promote osseointegration at the bone cement interface whilst maintaining antibiotic elution, anti-microbiological efficacy and cement mechanical properties. Prosthetic joint infection and aseptic loosening are associated with significant morbidity. Antibiotic loaded bone cement is commonly used and successfully reduces infection rates; however, there is increasing resistance to the commonly used gentamicin. Previous studies have shown gentamicin incorporated into bone cement using liposomes can maintain the cement's mechanical properties and improve antibiotic elution. The phospholipid phosphatidyl-l-serine has been postulated to encourage surface osteoblast attachment and in a liposome could improve osseointegration, thereby reducing aseptic loosening. Preliminary clinical isolate testing showed excellent antimicrobial action with amoxicillin therefore the study aims were to test amoxicillin incorporated into bone cement using liposomes containing phosphatidyl-l-serine in terms of antibiotic elution, microbiological profile and mechanical properties. Methods. Amoxicillin was encapsulated within 100nm liposomes containing phosphatidyl-L-serine and added to PMMA bone cement (Palacos R (Heraeus Medical, Newbury, UK)). Mechanical testing was performed according to Acrylic Cement standards (ISO BS 5833:2002). Elution testing was carried out along with microbiological testing utilising clinical isolates. Results. Liposomal encapsulated amoxicillin PMMA bone cement exceeded minimum ISO BS 5833:2002 standards, had better elution at 12.9% when compared with plain amoxicillin (p=0.036 at 48 hours) or commercial gentamicin cement (Palacos R+G, Heraeus Medical, Newbury, UK – previous studies showed 6% elution over the same time period). Amoxicillin showed superior antimicrobial action when compared with gentamicin of the same concentration. However, liposomal encapsulated amoxicillin in solution and liposomal encapsulated amoxicillin in PMMA were both less effective than free amoxicillin in bacterial growth inhibition. The liposomal amoxicillin also seemed to decrease the cement setting time. Conclusions. Phosphatidyl-l-serine containing liposomes maintained the cement's mechanical properties and seemed to have better antibiotic elution, however, had less effective antibacterial action than plain amoxicillin. This difference in antibacterial action requires further investigation along with investigation of osteoblast attachment to phosphatidyl-l-serine containing liposomes within cement. Plain amoxicillin, for those not penicillin allergic, seems to be a credible alternative to gentamicin for incorporation in PMMA bone cement. It has shown superior antibacterial action, which may improve infection rates, whilst maintaining the cement's mechanical properties

Introduction. Over 40-years the dominant form of implant fixation has been bone cement (PMMA). However the presence of circulating PMMA debris represents a 3rd-body wear mechanism for metal-on-polyethylene (MPE). Wear studies using PMMA slurries represent tests of clinical relevance (Table 1). Cup designs now use many varieties of highly-crosslinked polyethylene (HXPE) of improved wear resistance. However there appears to be no adverse wear studies of vitamin-E blended cups.1–4 The addition of vitamin E as an anti-oxidant is the currently preferred method to preserve mechanical properties and ageing resistance of HXPE. Therefore the present study examined the response of vitamin-E blended liners to PMMA abrasion combined with CoCr and ceramic heads. The hip simulator wear study was run in two phases to compare wear with, (i) clean lubricants and (ii) PMMA slurries. Methods. The vitamin-e blended polyethylene liners (HXe+) were provided by DJO Surgical (Austin, TX) with 40mm CoCr and ceramic femoral heads (Biolox-delta). Polyethylene liners were run in standard “Inverted” test. (Table 1) All cups were run in ‘clean’ serum lubricant for 6-million load cycles (6Mc)5 and in a debris slurry (PMMA: 5mg/ml concentration) for 2Mc.4 A commercial bone cement powder was used as “abrasive” (Biomet, Warsaw, IN). PMMA slurries were added at test intervals 6, 6.5, 7 and 7.5Mc.4 Wear was assessed gravimetrically and characterized by linear regression. Bearing roughness was analyzed by interferometry and SEM. Results. The acetabular cups showed low wear-rates to 6Mc duration with both ceramic and CoCr heads (Fig. 1). The debris slurries created much higher wear-rates, whereas control liners continued as before (Table 2). Discussion. This is the 1st study of vitamin-E blended polyethylene under 3rd-body wear conditions. With clean lubricant conditions, CPE combination wore approximately 50% less than MPE combination. Under abrasive lubricant conditions, CPE and MPE combinations wore at approximately same rate but more than an order of magnitude greater than the clean test phase. This was typical of such PMMA abrasion tests (Table 1). However there are no guidelines as to optimal choice of particulate type, morphology, dosage, frequency of injection or duration of test intervals (Table 1). The production of particulates in vivo is an unpredictable phenomenon and consequently laboratory simulation is fraught with uncertainties.6 On completion of the abrasive challenge (6–8Mc duration), our study will continue under clean conditions to 10Mc to define the important recovery phase of the vitamin-E blended polyethylene.3

Aim. To improve the challenging treatment of periprosthetic joint infections (PJI), researchers are constantly developing new handling methods and strategies. In patients with PJI after total knee arthroplasty (TKA) and severe local or systemic comorbidities, a two-stage exchange using a temporary antibiotic loaded PMMA-spacer is considered gold standard. This method has undisputed advantages, however, the increased risk of biofilm formation on the spacer surface, bone defects and soft tissue contractions after a six-week spacer interval are severe limitations. Our hypothesis is that a vacuum sealed foam in combination with constant instillation of an antiseptic fluid can address these drawbacks due to a significantly reduced spacer interval. Method. A pilot study was conducted in five PJI cases after TKA with severe comorbidities and/or multiple previous operations to evaluate the feasibility and safety of the proposed method. In the first step, surgical treatment included the explantation of the prosthesis, debridement, and the implantation of the VeraFlo-Dressing foam. The foam is connected to the VAC-Instill-Device via an inflow and an outflow tube. The surgical site is sealed airtight with the VAC-film. During the next 5 days, an antiseptic fluid (Lavasorb® or Taurolidine®) is instilled in a 30-minute interval using the VAC-Instill-Device. The limb is immobilized (no flexion in the knee joint, no weight bearing) for five days. Following that, the second operation is performed in which the VAC-VeraFlo. TM. -Therapy System is explanted and the revision TKA is implanted after debridement of the joint. Results. No serious adverse event occurred during the VAC-Instill spacer treatment. The TKA revision was performed after a mean of 5.4 ± 1.9 days. Mean patient age was 71±6 years with a mean of 6 previous PJI surgeries. Host classification according to McPherson was I/B/3, III/B/3 and III/C/3 in three cases. Out of the five cases included, four were successfully treated and remained infect free to date (mean 14.2 ± 12 months; germs: methicillin-resistant s. aureus, e. coli, staph. lugdunensis and one culture neg.). One case with candida infection of a total femur prosthesis had to be treated with an enucleation of the hip due to rising inflammation parameters and signs of sepsis 7 days after VAC-Instill implantation. Conclusions. The presented data on the VAC-Instill spacer method in septic two-stage revision TKA show promising results regarding feasibility and safety. A prospective randomized controlled examination is in progress to evaluate the possible advantages over a two-stage approach using a standard PMMA spacer

INTRODUCTION. Joint replacement is one of the most common orthopaedic procedures, with over 2 million surgeries performed each year across the globe. Loss of implant fixation, or aseptic loosening, is the leading cause of revision following primary joint replacement, accounting for ∼25% of all revision cases [1]. However, diagnosis of aseptic loosening and its underlying causes remain challenging due to the low sensitivity and specificity of plain radiographs. To address this, we propose a novel approach inspired by [2] involving the use of a self-sensing bone cement (by imparting strain-dependent electrical conductivity or piezoresistivity) combined with electrical impedance tomography (EIT). Piezoresistivity is imparted to cement via incorporation of micro/nanoscale conductive fillers. Therefore mechanical effects such as loosening and cracks will manifest as a conductivity change of the cement. This work explores if EIT is able to detect strains and cracks within the bone cement volume. METHODS. Experiments were designed to determine whether EIT combined with piezoresistive cement can be used to detect strains and cracks (Fig. 1). The setup consists of a tank filled with water, 16 electrodes, sample, a loading machine (MTS), and an EIT system. To develop the piezoresistive bone cement, microscale carbon fibers were used with varying CF/PMMA volumetric ratios (VR) from VR = 0.25% to 3.0%. Three conical samples were made to model a loading condition similar to knee implants (Fig. 1). The samples were compressed while the conductivity map of the tank was measured with the EIT system. RESULTS. Figure 2 shows the conductivity of the piezoresistive bone cement with respect to the CF/PMMA VR, the percolation happens at VR = 1.0% and the maximum gradient occurs at VR = 1.5%. Three conical samples were built and experimented to examine the hypothesis. The samples were loaded from F = 0 to F = 4000 N for the strain measurement and then loaded until the first crack initiates. Figure 3 (a) and (b) show the conductivity difference map measured by EIT for strain measurement and crack detection respectively. It can be seen in Fig. 3(a) that due to the shear stresses within the bone cement the conductivity of the sample decreases under compression. At the crack initiation the conductivity of the samples increases significantly (Fig. 3(b)). Figure 3(c) shows evolution of sample conductivity difference measured by EIT as a function of the applied load, VR = 1.5% shows the largest sensitivity. DISCUSSION. The results validate our hypothesis; both cracks and strains resulted in electrical conductivity changes measurable by EIT. While these initial results are encouraging, the approach must be validated via testing of surrogate and cadaver bones in an EIT phantom. If successful, this approach could for the first time provide means of in-vivo studying of aseptic loosening, leading to a paradigm shift in the understanding of this important clinical problem. For any figures or tables, please contact the authors directly

BACKGROUND. This scientific work is a non-interventional, experimental and prospective comparative study of two very high-viscosity PMMA bone cements: DePuy CMW 2G and Palacos® fast R+G. Reference product: Palacos® R+G. Fast-setting PMMA bone cements are used in the endoprothetics of the patella and knee (in Australia) and are also used to cement an artificial acetabulum (in the UK). Are there any differences regarding the characteristics of the two fast-setting PMMA bone cements?. MATERIALS AND METHODS. All cements were mixed as specified by the manufacturer and analysed on the following parameters: handling properties (mixing, waiting, working and hardening phase), powder/liquid-ratio, mechanical properties (ISO 5833:2002 and DIN 53435), fatigue strength (ISO 16402) and elution profile. All tests were done in an acclimatised laboratory with temperatures set at 23.5°C ± 0.5°C and a humidity of >40%. Of two batch numbers, 11 units of each bone cement were tested. RESULTS AND DISCUSSION. The handling properties of the two tested PMMA bone cements Palacos® fast R+G and CMW 2G are highly similar (n=12). CMW 2G reaches the mixing and waiting phase approximately 20s later than Palacos® fast R+G. Palacos® fast R+G has a similar working, but a shorter hardening phase than CMW 2G. In addition, working with Palacos® fast R+G was advantageous due to its green dye. Palacos® fast R+G has a higher powder/liquid-ratio of 2.550. Due to the higher powder percentage, the cement has a shorter mixing and waiting phase than CMW 2G with a ratio of 2:1. Both analysed bone cements fulfil the quasi-static properties of ISO 5833:2002 and DIN 53435. Palacos® fast R+G was far superior in its ISO compressive strength (MPa) shown through one-way analysis of variance (ANOVA) (p<0.01) and independent two sample t-test (p<0.01) at 0.05 level of significance (n=20)(Fig. 1). CMW 2G has a higher quasi-static ISO bending strength (MPa) than Palacos® fast R+G, but the same test shows a much higher fatigue strength (ISO 16402) of Palacos® fast R+G (n=5) (Fig. 2). Palacos® R+G and Palacos® fast R+G show a similar elution profile (n=3), whereas CMW 2G shows a much lower antibiotic elution over time. CMW 2G releases approximately 1/3 of gentamicin per mould body after 24h. After day 3 and 5, CMW 2G has a significantly lower gentamicin release than Palacos® fast R+G (Fig. 3). Palacos® fast R+G has a higher gentamicin release, due to its hydrophilic polymer basis, which is identical to Palacos® R+G. CMW 2G contains pure PMMA and is therefore more hydrophobic than the other two tested cements. CONCLUSION. Handling with Palacos® fast R+G was advantageous due to its green dye. Because of the shorter handling phases of Palacos® fast R+G, it is superior as it minimises the length of surgeries. Mechanical properties according (ISO 5833:2002 and DIN 53435) were comparable. Palacos® fast R+G has a statistically significant higher ISO compressive strength (MPa). Palacos® fast R+G also showed higher fatigue strength (ISO 16402). Palacos® fast R+G was far superior in matters of gentamicin release over time

Is is believed that 3rd-body wear of polyethylene, be it from particles of bone, bone-cement (PMMA), or metal, is an unavoidable risk in total hip arthroplasty (THA). Simulator studies have demonstrated that wear in conventional polyethylene (CXPE) and highly crosslinked polyethylene (HXPE) cups increased 6 and 20-fold respectively when challenged by circulating 3. rd. -body PMMA particulates. There was no corresponding change in head roughness, i.e. the PMMA did not roughen CoCr surfaces. Many contemporary cup designs now use the vitamin-E process combined with higher crosslinking dosage (VEPE). However, little if anything is known about the VEPE debris. Therefore in this study we analyzed the morphology of VEPE particles from cups that had been run in, a) standard simulator test mode and b) adverse PMMA debris-challenge mode. The aim of this study was to determine how a clinically relevant challenge, such as addition of PMMA particles affected the wear debris. This had not been attempted previously due to contamination polyethylene by PMMA debris. The hypotheses were that, a) during the ‘clean’ test, VEPE would yield smaller debris of standard globular shape compared to controls (XPE) and b) in adverse PMMA challenge mode, VEPE debris size would increase and become more flake-like. The XPE and vitamin-E blended cups (VEPE) cups were gamma-irradiated at 7.5 Mrad and 15 Mrad, respectively. Cups were run Inverted and mated with ceramic femoral heads of diameter 44 mm (Biolox-delta, Ceramtec). The three test phases included; ‘clean’ for 6 million cycles (6 Mc), abrasive slurry 6–8 Mc (concentration 10g/L), and ‘clean’ 8–10 Mc. The debris was isolated using standard procedure for ‘clean’ tests and a modified procedure for the abrasive slurries. Particles were imaged using SEM and the micrographs analyzed (Image J). Approximately 600 particles were analyzed from each sample (4.5 Mc and 8 Mc) and morphology defined via aspect ratio (AR), equivalent circular diameter (ECD), and circular shape factor (CSF). The clean test revealed slight differences in shape factors for XPE and VEPE (AR, CSF within 30%: p <0.0001) but none with regard to size (p > 0.9999). The median ECD for both XPE and VEPE was approximately 0.55 μm. The abrasive test revealed a statistical difference (p < 0.0001) in shape compared to the clean test, but varied less than 25%. The greater change in debris morphology between the abrasive test and clean test was size, which increased 3.6 fold for VEPE particles (ECD = 2.0 μm) and 4.3 fold for XPE particles (ECD = 2.3 μm). It was determined that addition of vitamin E to the PE did not change the size, but did change the shape of PE debris particles up to 30%. This study was the first to isolate debris particles during an abrasive slurry test and determine morphology under such conditions. Debris particles formed in abrasive conditions were found to be 4-fold larger in diameter, suggesting a larger volume of shreds in comparison to the mostly submicron population observed under standard testing conditions. Figure 1: Boxplot of equivalent circular diameter values. Figure 2: Boxplot of aspect ratio values. Figure 3: Boxplot of circular shape factor values

Recent clinical data suggest improvement in the fixation of tibia trays for total knee arthroplasty when the trays are additive manufactured with highly porous bone ingrowth structures. Currently, press-fit TKA is less common than press-fit THA. This is partly because the loads on the relatively flat, porous, bony apposition area of a tibial tray are more demanding than those same porous materials surrounding a hip stem. Even the most advanced additive manufactured (AM) highly porous structures have bone ingrowth limitations clinically as aseptic loosening still remains more common in press-fit TKA vs. THA implants. Osseointegration and antibacterial properties have been shown in vitro and in vivo to improve when implants have modified surfaces that have biomimetic nanostructures designed to mimic and interact with biological structures on the nano-scale. Pre-clinical evaluations show that TiO. 2. nanotubes (TNT), produced by anodization, on Ti6Al4V surfaces positively enhance the rate at which osseointegration occurs and TNT nano-texturization enhances the antibacterial properties of the implant surface. 2. In this in vivo sheep study, identical Direct Metal laser Sintered (DMLS) highly porous Ti6Al4V specimens with and without TNT surface treatment are compared to sintered bead specimens with plasma sprayed hydroxyapatite-coated surface treatment. Identical DMLS specimens made from CoCrMo were also implanted in sheep tibia bi-cortically (3 per tibia) and in the cancellous bone of the distal femur and proximal tibia (1 per site). Animals were injected with fluorochrome labels at weeks 1, 2 and 3 after surgery to assess the rate of bone integration. The cortical specimens were mechanically tested and processed for PMMA histology and histomorphometry after 4 or 12 weeks. The cancellous samples were also processed for PMMA histology and histomorphometry. The three types of bone labels were visualized under UV light to examine the rate of new bony integration. At 4 weeks, a 42% increase in average pull-out shear strength between nanotube treated specimens and non-nanotube treated specimens was shown. A 21% increase in average pull-out shear strength between nanotube treated specimens and hydroxyapatite-coated specimens was shown. At 12 weeks, all specimens had statistically similar pull-out values. Bone labels demonstrated new bone formation into the porous domains on the materials as early as 2 weeks. A separate in vivo study on 8 rabbits infected with methicillin-resistant Staphylococcus aureus showed bacterial colonization reduction on the surface of the implants treated with TNT. In vitro and in vivo evidence suggests that nanoscale surfaces have an antibacterial effect due to surface energy changes that reduce the ability of bacteria to adhere. These in vivo studies show that TNT on highly porous AM specimens made from Ti6Al4V enhances new bone integration and also reduce microbial attachment

In the 1960's Sir John Charnley introduced to clinical practice his low friction arthroplasty with a highly polished cemented femoral stem. The satisfactory long term results of this and other cemented stems support the use of polymethylmethacrylate (PMMA) for fixation. The constituents of PMMA remain virtually unchanged since the 1960s. However, in the last three decades, advances in the understanding of cement fixation, mixing techniques, application, pressurization, stem materials and design provided further improvements to the clinical results. The beneficial changes in cementing technique include femoral preparation to diminish interface bleeding, pulsatile lavage, reduced cement porosity by vacuum mixing, the use of a cement restrictor, pre-heating of the stem and polymer, retrograde canal filling and pressurization with a cement gun, stem centralization and stem geometries that increase the intramedullary pressure and penetration of PMMA into the cancellous structure of bone. Some other changes in cementing technique proved to be detrimental and were abandoned, such as the use of Boneloc cement that polymerised at a low temperature, and roughening and pre-coating of the stem surface. In the last two decades there has been a tendency towards an increased use of cementless femoral fixation for primary hip arthroplasty. The shift in the type of fixation followed the consistent, durable fixation obtained with uncemented acetabular cups, ease of implantation and the poor results of cemented femoral fixation of rough and pre-coated stems. Unlike cementless femoral fixation, modern cemented femoral fixation has numerous advantages: it is versatile, durable and can be used regardless of the diagnosis, proximal femoral geometry, natural neck version, and bone quality. It can be used in combination with antibiotics in patients with a history or predisposition for infection. Intra-operative femoral fractures are rare. However, the risk may be increased in collarless polished tapered stems. Post-operative thigh pain is extremely rare. Survivorship has not been surpassed by uncemented femoral fixation and it continues to be my preferred form of fixation. However, heavy, young, male patients may exhibit a slightly higher aseptic loosening rate

Aims. Calcium sulphate (CaSO. 4. ) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO. 4. as an adjunct to the routine therapy of bone and joint infections. Patients and Methods. A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip. Results. The overall systemic exposure remained within a safe range, even in patients with post-operative renal failure, none requiring removal of the pellets. Local concentrations were approximately ten times higher than with polymethylmethacrylate (PMMA) as a carrier, but remained below reported cell toxicity thresholds. Decreasing concentrations in wound fluid were observed over several weeks, but remained above the common minimum inhibitory concentrations for Staphylococcus up to three months post-operatively. . Conclusion. This study provides the first pharmacokinetic description of the local application of vancomycin with CaSO. 4. as a carrier, documenting slow release, systemic safety and a release profile far more interesting than from PMMA. In particular, considering in vitro data, concentrations of vancomycin active against staphylococcal biofilm were seen for several weeks. Cite this article: Bone Joint J 2017;99-B:1537–44

The aim of the present study was to assess the antibiofilm activity of daptomycin- and vancomycin-loaded poly(methyl methacrylate) (PMMA) and PMMA-Eudragit RL100 (EUD) microparticles against mature biofilms of polysaccharide intercellular adhesin-positive S. epidermidis. The effect of plain, daptomycin- and vancomycin-loaded PMMA and PMMA-EUD microparticles on S. epidermidis biofilms was assessed by isothermal microcalorimetry (IMC) and fluorescence in situ hybridization (FISH). Biofilms were grown for 48h onto poly-urethane pieces of fixed dimensions. Each sample was washed with PBS in order to remove planktonic bacteria and incubated for 24h with different concentrations of acrylic microparticles (20–1.25 mg/mL). The minimal biofilm inhibitory concentration (MBIC) of the antibiotic-loaded particles was defined as the lowest concentration of particles that was able to prevent heat flow associated to the recovery of the biofilms. After incubation with the microparticles, sessile cocci were hybridized with the pan-bacterial EUB338-FITC and the staphylococci-specific STAPHY-FICT probes and stained with DAPI. Biofilm structure and metabolic state were characterized by fluorescence microscopy. According to the IMC results, plain PMMA-particles showed no effect on S. epidermidis biofilms, whereas PMMA-EUD-microparticles negatively influenced the recovery of the biofilm probably due to the highly positive charge of these particles. The MBIC of daptomycin-loaded PMMA-microparticles was 20 mg/mL, whereas vancomycin-loaded PMMA microparticles were not able to inhibit biofilm recovery. Adding EUD to the formulation reduced the MBIC of daptomycin-loaded microparticles to 1.25 mg/mL, corresponding to a 16-fold reduction. Regarding the vancomycin-loaded microparticles, EUD caused a further decrease of their antibiofilm activity. The FISH micrographs corroborated the IMC results and provided additional insights on the antibiofilm effect of these carriers. According to FISH, daptomycin-loaded PMMA-EUD microparticles were responsible for the most pronounced reduction in biofilm mass. In addition, FISH showed that both PMMA and PMMA-EUD microparticles were able to attach to the biofilms. Adding EUD to the formulations proved to be a powerful strategy to improve daptomycin-loaded microparticles antibiofilm activity. In addition, the combination of IMC and FISH was essential in order to fully assess the effect of polymeric microparticles on sessile S. epidermidis. Although the present study enabled gaining further insights on this subject, the nature of these interactions remains unclear. However, this may be a crucial aspect for the enhancement of antibiofilm activity of antibiotic-loaded polymeric microcarriers against mature biofilms. This work was supported by the Portuguese government (Fundação para a Ciência e a Tecnologia) and FEDER (grant SFRH/BD/69260/2010 and research project EXCL/CTM-NAN/0166/2012) and strategic project PEst-OE/SAU/UI4013/2011