Aim. To evaluate bacterial adhesion and biofilm formation to metallic cerclage wire versus polymer cerclage system (SuperCable®). Methods. Experimental in vitro study to evaluate quantitative bacterial adherence to different cerclage wire materials. Two types of cerclage wires were compared: a metallic versus a polymer based wire (SuperCable®). A two-centimeter cerclage wire piece of each material was included in 2 mL of tryptic soy broth (TSB) culture media, inoculated with 10 microliters of a 0.5 McFarland of a Staphylococcus epidermidis strain and cultivated at 37°C during 2h for adhesion and 48h for biofilm formation. After this time, the cerclages were washed using a 1% phosphate buffered saline (PBS) and sonicated in new culture medium. After sonication, dilutions of each culture were spread in TSB agar and incubated 37°C during 24h. The number of colonies were counted and the cfu/cm2 was calculated. Results. There were no differences in the number of colonies counted at 2 hours. At 48 hours, the polymer cerclage system showed a clinically and statistically reduction of 95.2% in the biofilm formation of S. epidermidis. The highest bacterial counts were observed in metallic cerclages after 48h. Conclusion. In in vitro conditions, the polymer cerclage system may offer decreased biofilm formation compared with metallic cerclage wires. However, there are many other factors in in vivo conditions that could play a role in bacterial adhesion to cerclage wires. Further research is needed in order to recommend the use of polymer cerclage systems for septic revision surgery

Introduction. Stress shielding and wear induced aseptic loosening cause failure in total joint arthroplasty. To improve long-term outcomes in total knee arthroplasty (TKA), the use of a low modulus, low wearing biomaterial may be a suitable alternative to cobalt chromium (CoCr) femoral components. Based on its favorable mechanical properties and observed clinical success especially in spinal surgery, polyetheretherketone (PEEK) is investigated as a candidate material for a metal free TKA. An all polymer TKA has several theoretical advantages, these include a more physiological stress in the distal femur, elimination of biological reaction to metal, better radiographic visualisation of the bone implant interface especially with CT and MRI. In addition, polymers afford a cheaper option for the manufacture of prostheses. Aims and Hypothesis. This study investigated the wear performance of PEEK and carbon reinforced PEEK (CFR-PEEK) as bearing materials in an all polymer TKA using a unidirectional pin on plate test. Our hypothesis was that reduced wear is generated from PEEK or CFR-PEEK bearings when compared with metal on polyethylene (MoP) bearings and that this combination may provide a suitable alternative in TKA. Methods. A validated modification of ASTM F7321 was used as test protocol. Twenty millimeter diameter spherically ended pins with a radius of 25mm were articulated against 40mm diameter plates. A load of 1000N was applied to generate an initial contact stress of ∼70MPa similar to high contact stresses previously reported in non congruent knee designs2. Ten material combinations were tested as shown in Table 1. Table 1: Tribological couples tested (Pin vs. Plate) UHMWPE – ultrahigh molecular weight polyethylene, XLPE – highly cross-linked polyethylene). The lubricant used was 25% newborn calf serum containing 0.3% sodium azide to retard bacteria growth and 20mM EDTA to prevent calcium deposition. Three repeats of pin on plate combinations (including 2 passive soak controls) were tested for 2 million cycles at a cycle frequency of 1Hz and a cycle length of 20 mm. Gravimetric wear was analysed every 250,000 cycles and results converted to volumetric wear using material density. Results. All CFR-PEEK articulations were stopped due to excessive wear of the counter-surfaces. Results showed a linear wear rate of UHMWPE and XLPE plates over the test period. PEEK vs. XLPE showed similar wear rates to metal on polyethylene (MoP)bearings (Fig 1). Conclusion. At high stresses representative of non conforming knee designs, PEEK pins articulated against XLPE plates generated volumetric wear similar to that noted in MoP bearings. From these results, it may be possible to replace CoCr in TKR with PEEK which may be beneficial because of the low elastic modulus and elimination of biological activity to metal alloy

Introduction. Acetabular component loosening has been one of the factors of revision of total hip arthroplasty (THA). Inadequate mechanical fixation or load transfer may contribute to this loosening process. Several reports showed the load transfer in the acetabulum by metal components. However, there is no report about the influence of the joint surface on the load transfer. We developed a novel acetabular cross-linked polyethylene (CLPE) liner with graft biocompatible phospholipid polymer(MPC) on the surface. The MPC polymer surface had high lubricity and low friction. We hypothesized the acetabular component with MPC polymer surface (MPC-CLPE) may reduce load transfer in the acetabulum compared to that of the by CLPE acetabular component without MPC. Methods. We fixed the three cement cup with MPC-CLPE (Group M; sample No.1–3) and three cement cup with CLPE (Group C; sample No.4–6) placed in the synthetic bone block with bone cement with a 0.10mm thick arc-shaped piezoresistive force sensor, which can measure the dynamic load transfer(Tekscan K-scan 4400; Boston). (Fig 1) A hip simulator (MTS Systems Corp., Eden Prairie, MN) was used for the load transfer test performed according to the ISO Standard 14242-1. Both groups had same inner and outer diameter s of 28 and 50mm, respectively. A Co–Cr alloy femoral head with a diameter of 28 mm (K-MAXs HH-02; KYOCERA Medical Corp.) was used as the femoral component. A biaxial rocking motion was applied to the head/cup interface via an offset bearing assembly with an inclined angle of +20. Both the loading and motion were synchronized at 1 Hz. According to the double-peaked Paul-type physiologic hip load, the applied peak loads were 1793 and 2744 N described in a previous study. The simulator was run 3 cycles. We recorded both the peak of the contact force and the accumulation of the six times load in total. Secondly, we calculated the mean change of the load transfer. We used the Student t-test. P value < 0.05 was used to determine statistical significance. We used EZR for statistical analysis. Results. The mean of total accumulation of the load transfer in the group M is significantly lower than that of in the group C. (7037±508 N vs 11019±1290 N, P<0.0001). The peak of load in the group M was also significantly lower than that in the group C. (1024±166 N vs 1557±395 N) (Fig 2)The mean of the change of the load transfer in the group M is significantly lower than that of in the group C. (2913±112 N vs 4182±306 N) (Fig 3). Conclusion. The acetabular component with MPC surface could reduce and prevent the radical load transfer change toward to the acetabulum compared to CLPE acetabular component without MPC. For any figures or tables, please contact the authors directly

Aims. Impaction bone grafting with milled human allograft is the gold standard for replacing lost bone stock during revision hip surgery. Problems surrounding the use of allograft include cost, availability, disease transmission and stem subsidence (usually due to shear failure of the surrounding allograft). The aim of this study was to investigate various polymers for use as substitute allograft. The ideal graft would be a composite with similar mechanical characteristics as allograft, and with the ability to form de novo bone. Methods. High and low molecular weight (MW) forms of three different polymers (polylactic acid (PLA), poly (lactic co-glycolic) acid (PLGA) and polycaprolactone (PCL)) were milled, impacted into discs, and then tested in a custom built shear testing rig, and compared to allograft. A second stage of the experiment involved the addition of skeletal stem cells (SSC) to each of the milled polymers, impaction, 8 days incubation, and then tests for cell viability and number, via fluorostaining and biochemical (WST-1) assays. Results. The shear strengths of both high/low MW PLA, and high/low MW PLGA were significantly higher than those of milled allograft (P< 0.001, P< 0.001, P< 0.005 and P< 0.005) but high and low MW PCL was poor to impact, and had significantly lower shear strengths (P< 0.005, P< 0.001). Fluorostaining showed good cell survival on high MW PLA, high MW PCL and high MW PLGA. These findings were confirmed with WST-1 assays. Conclusions. High MW PLA as well as high MW PLGA performed well both in mechanical testing and cell compatibility studies. These two polymers are good contenders to produce a living composite for use as substitute human allograft in impaction bone grafting, and are currently being optimised for this use via the investigation of different production techniques and in-vivo studies

Reducion of friction between bearing surfaces in Total Hip Arthroplasty is a main target of biological tribology. MPC (2-Methacryloyloxyethyl phosphorylcholine) has a similar properties to those of cell membranes, and can reduce friction with fluid luburication. We have used crosslink polyethylene with MPC polymer coating for primary and revision THA since 2011. Eighty one cementless THA were performed with closslink polyethlene liner with MPC polymer in our hospital. We have examined 21 cases which were followed for more than one year. Eighteen cases for primary THA and three for revision THA, and 3 were male and 18 were female. Seventeen cases were osteoarthritis, two osteonecrosis of femoral head and two rheumatoid arthritis. Average age of patients at THA was 60.4 years old. In the OR, we have experienced a very wet and slippery feeling on the bearing surface of polyethylene liner every time. Surface touch is similar to skin with lotions. No wear were measured on the X-ray display and no infections and no fractures were occurred during follow up. MPC polymer coating in THA can be useful for reduction of friction and generation of wear debris

Friction between bearing surfaces in Total Hip Arthroplasty has been a main target of applied tribology. MPC (2-Methacryloyloxyethyl phosphorylcholine) has a similar properties to those of cell membranes, and can reduce friction with fluid lubrication in wet environment. We have used crosslink polyethylene with MPC polymer coating for primary and revision THA since 2011. We have examined 19 cases which were followed for more than two years. Sixteen cases for primary THA and three for revision THA, and 3 were male and 16 were female. Sixteen cases were osteoarthritis, one osteonecrosis of femoral head and two rheumatoid arthritis. Average age of patients at THA was 60.1 years old. In the OR, we have experienced a very wet and slippery feeling on the bearing surface of polyethylene liner. Surface touch is similar to hard surface with oil or lotions. No PE wear were measured on the X-ray display and no infections and no fractures were occurred during follow up. MPC polymer coating in THA can be useful for reduction of friction and generation of wear debris

To improve the longevity of total hip replacements (THR), it is necessary to prevent wear of the ultra-high molecular weight polyethylene (UHMWPE) bearing, as wear debris can cause osteolysis and aseptic loosening. Highly cross-linked UHMWPE reduces wear, sometimes stabilized with vitamin E to preserve its mechanical properties and prevent oxidative degeneration. An extra novel solution has been grafting the surface of UHMWPE with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC). This treatment uses a hydrophilic (wettable) phospholipid polymer to improve lubrication and reduce friction and wear of the bearing material. We set out to test the wear and friction of ceramic-on-polyethylene (COP) THRs that had the PMPC surface treatment, or left untreated for control. Four groups of UHMWPE bearings were tested against identical 40mm ceramic heads (zirconia-toughened alumina). The UHMWPE bearings were highly cross-linked with/without vitamin E (HXL Vit. E: 125 kGy radiation dose / HXL: 75 kGy). In each group, half underwent the PMPC treatment (n = 3 for all four groups). Testing was conducted on an AMTI hip simulator for 10 million walking cycles of ISO-14242-1, at 1 Hz, with diluted bovine serum (30 g/L protein concentration) as lubricant, at 37ºC, and with fluid absorption errors corrected with active soak controls. Using a previously published method, frictional torques and a frictional factor around three orthogonal axes about the femoral head were measured/computed, by data processing of the measurements of a 6-DOF load cell on each station of the hip simulator. Such friction measurements and stops for specimen weighing were carried out at regular intervals throughout the wear test. The HXL liners without and with the PMPC treatment wore at 5.86±0.402 mg/Mc and 1.70±1.36 mg/Mc, respectively (p=0.013) (Fig. 1). The HXL Vit. E liners without and with the PMPC treatment wore at 2.14±0.269 mg/Mc and 0.736±0.750 mg/Mc, respectively (p=0.035). The wear rates of the untreated HXL and HXL Vit. E liners were significantly different (p=0.0002) but no difference in wear rate was found between the two PMPC treated groups (p=0.179), although, as mentioned above, the PMPC treatment very significantly reduced wear in each case. The ceramic femoral heads showed little wear (weight loss) themselves. In general, the THRs showed decreasing friction over the 10 Mc, with the PMPC types showing a slight increase in friction towards the end of the test (Fig. 2). PMPC HXL liners showed the lowest friction factor (0.022±0.001) which was significantly lower (p<0.001) than the friction of the untreated liners (0.028±0.002) (Fig. 3). The PMPC HXL Vit. E liners showed lower friction factors than the untreated HXL Vit. E liners (0.034±0.002, 0.036±0.004, respectively), although this difference was not significant (p=0.116). Overall, the liners with the PMPC treatment displayed statistically significantly lower friction factors (p=0.003) than those untreated. The coincidence of some reduction of surface friction with larger wear reduction obviously suggests some but not necessarily full causality. PMPC successfully reduced both the friction and the wear in these COP THRs during this extended 10 Mc test. This likely would translate to improved implant longevity in patients. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Artificial knee joints are continuously loaded by higher contact stress than artificial hip joints due to a less conformity and much smaller contact area between the femoral and tibial surfaces. The higher contact stress causes severe surface damage such as pitting or delamination of polyethylene (PE) tibial inserts. To decrease the risks of these surface damages, the oxidation degradation of cross-linked polyethylene (PE) induced by residual free radicals resulting from gamma-ray irradiation for cross-linking or sterilization should be prevented. Vitamin E (VE), as an antioxidant, blended PE (PE(VE)) has been used to solve the problems. In addition, osteolysis induced by PE wear particles, bone cement and metallic debris is recognized as one of the important problems for total knee arthroplasty (TKA). To decrease the generation of PE wear particles, we have developed the bearing surface mimicking the articular cartilage; grafting a biocompatible polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), onto the PE surface having high wear resistance. In this study, we have evaluated the surface, mechanical under severe oxidative condition, and wear properties of PMPC-grafted cross-linked PE(VE) (PMPC-CLPE(VE)) material for artificial knee joints. Untreated and PMPC-grafted 0.1 mass% VE-blended PE (GUR1020E resin) with a gamma-ray irradiation of 100 kGy for cross-linking and 25 kGy for sterilization were prepared (CLPE(VE) and PMPC-CLPE(VE), respectively). Surface properties were evaluated by Fourier-transform infrared (FT-IR) spectroscopy and transmission electron microscope (TEM) observations. Surface wettability and frictional property were measured by static water contact angle measurement and ball-on-plate friction test. To evaluate the oxidation degradation resistance, mechanical and physical properties such tensile test, izod impact test, small punch test and cross-link density measurement before and after accelerated aging were measured. Wear properties of the tibial inserts were examined by using knee simulator in the combination of Co-Cr-Mo femoral components according to ISO14243-3. Gravimetric wear, volumetric penetration and the number of generated wear particles were measured. By the FT-IR measurements and TEM observation, P–O peaks attributed to MPC unit and uniform PMPC layer with 100–200 nm thick was observed only on PMPC-CLPE(VE) surface. Static water contact angle of CLPE(VE) was almost 100 degree, while that of PMPC-CLPE(VE) decreased significantly to almost 35 degree. There was no significant difference in the mechanical and physical properties between CLPE(VE) and PMPC-CLPE(VE). Moreover, both the CLPE(VE) and PMPC-CLPE(VE) maintained these properties even after the accelerated aging of 12 weeks [Fig. 1]. Blended VE in CLPE would act as radical scavengers to prevent oxidation degradation. In the knee simulator wear test, the PMPC-CLPE(VE) tibial inserts showed about a half gravimetric wear compared to the CLPE(VE) tibial inserts [Fig. 2]. This would be due to the significant differences observed in wettability of the surface. Water thin film formed on the hydrated PMPC graft layer, would act as significantly efficient lubricant. From these results, the PMPC-CLPE(VE) is expected to be one of the great bearing materials not only preventing surface damages due to higher contact stress and oxidation degradation but also improving wear resistance, and to provide much more lifelong artificial knee joints. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Introduction. Corrosion of the femoral head-trunnion junction in modular hip components has become a concern as the corrosion products may lead to adverse local tissue reactions. A simple way to avoid trunnion corrosion is to manufacture the femoral head with a non-metallic material, such as ceramics that are widely. An alternative solution may lie in advanced polymers like polyaryletherketones (PAEKs). These thermoplastics have high mechanical strength necessary for use as femoral heads in hip arthroplasty, but they must be tested to ensure that they do not adversely affect the wear of the ultrahigh molecular weight polyethylene (UHMWPE) liner counterface. Pin-on-disc (POD) wear testing has been extensively used to evaluate the wear properties of UHMWPE prior to more extensive and costly analysis with joint simulators. We hypothesized that the wear of crosslinked UHMWPE would not be adversely affected in POD tests when articulated against an advanced thermoplastic counterface. Methods. 0.1 wt.% VitE blended UHMWPE stock was e-beam irradiated to 100, 125, 140, 160, and 175 kGy and machined into cylindrical pins for testing. An additional group of 100 kGy e-beam irradiated and melted UHMWPE (with no vitamin E) was also machined and tested. Three different counterface materials were tested: (1) Cobalt-chrome (CoCr) with a surface roughness (R. a. ) of <0.5 μm, (2) Biolox™ ceramic (CeramTec), and (3) Polyetheretherketone (PEEK), a member of the PAEK family (Fig 1). A bidirectional POD wear tester [1] was used to measure the wear rate of UHMWPE specimens, where the specimens moved in a 10 mm × 5 mm rectangular pattern under a Paul-type load curve [2] synchronized with the motion. The peak load of the loading curve corresponded to a peak contact pressure of 5.1 MPa between each UHMWPE pin specimen and the counterface disc. Each test was conducted at 2 Hz in undiluted bovine serum stabilized with ethylenediamine tetraacetate (EDTA) and penicillin. The pins were cleaned and weighed daily, and a wear rate was calculated at the end of each test by linear regression. Results. As expected, higher radiation doses led to lower wear rates against all counterface materials (Fig 2). The PEEK discs produced the lowest UHMWPE wear in each group and the CoCr discs produced the highest UHMWPE wear; however, the two UHMWPE groups with the lowest wear rates showed no difference between the three counterface materials. Conclusions. Even though the PEEK discs had visible machining marks – that is they were not polished to an implant surface finish – they still yielded the lowest wear rates for UHMWPE articulating against them when compared to the highly polished and smooth CoCr and ceramic materials. Implementing further steps to better the surface roughness of the PEEK counterface may yield even better wear rates. Using PEEK in femoral heads may alleviate issues with trunnion corrosion without increasing the incidence of osteolysis or other wear related issues. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Introduction. Currently, different techniques to evaluate biocompatibility of orthopaedic materials, including two-dimensional (2D) cell culture for metal and ceramic wear debris and floating 2D surfaces or three-dimensional (3D) agarose gels for UHMWPE wear debris, are used. We have developed a single method using 3D agarose gels that is suitable to test the biocompatibility of all three types of wear debris simultaneously. Moreover, stimulation of the cells by wear particles embedded in a 3D gel better mimics the in vivo environment. Materials and Methods. Clinically relevant sterile UHMWPE and CoCr wear particles were generated using methodologies described previously [1,2]. Commercially available nanoscale and micron-sized silicon nitride (Si. 3. N. 4. ) particles (<50 nm and <1 μm, Sigma UK) were sterilised by heat treatment for 4h at 180°C. Agarose-particle suspensions were prepared by mixing warm 2% (w/v) low-melting-point agarose solution with the particles dispersed by sonication in DMEM culture media. The suspensions were then allowed to set at room temperature for 10 min in 96 well culture plates. Sub-confluent L929 murine fibroblasts were cultured on the prepared gels for up to 6 days in 5% (v/v) CO. 2. at 37°C. After incubation, the viability of cells was measured using the ATP-lite assay. The results were expressed as mean ± 95% confidence limits and the data was analysed using one-way ANOVA and Tukey-Kramer post-hoc analysis. Results and Discussion. The gels were observed to ensure uniform distribution of particles and migration of cells into the gel. No significant reduction in viability was observed for nanoscale and micron-sized Si. 3. N. 4. particles at low doses (0.5 μm. 3. per cell) and high doses (50 μm. 3. per cell), or for UHMWPE wear debris at high doses (100 μm. 3. per cell) [Figure1]. Moreover, the viability was significantly reduced for high doses of CoCr wear debris (50 μm. 3. per cell) and the positive control, camptothecin (2 μg.ml. −1. ) at day 6 [Figure1]. These results are consistent with the literature [2,3] and therefore validate our 3D agarose cell culture method for comparing cytotoxicity of polymer, metal and ceramic particles in a single assay, simultaneously. Conclusion. Biocompatibility ofpolymer, metal and ceramic wear debris can be tested simultaneously by using 3D particle embedded agarose gels. Acknowledgements. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. GA-310477 LifeLongJoints

Aim. Galleria mellonella larvae is a well-known insect infection model that has been used to test the virulence of bacterial and fungal strains as well as for the high throughput screening of antimicrobial compounds against infections. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections using small K-wire as implant material. Here, we aimed to further expand the use of G. mellonella to test other materials such as bone cement with combination of gentamicin to treat implant-associated infections. Method. The poly methyl methacrylate (PMMA) with and without gentamicin and liquid methyl methacrylate (MMA) were kindly provided by Heraeus Medical GmbH, Wehrheim. To make the bone cement implants as cubes, Teflon plate (Karl Lettenbauer, Erlangen) with specified well size was used. The Radiopaque polymer and monomer were mixed well in a bowl, applied over on to the Teflon plate and pressed with spatula to form fine and uniform cubes. After polymerization, the bone cement implants were taken out of the Teflon well plate with the help of pin. For the infection process, bone cement cubes were pre-incubated with S. aureus EDCC 5055 culture at 5×10. 6. CFU/ml for 30 min at 150 rpm shaking conditions. Later, these implants were washed with 10ml PBS and implanted in the larvae as mentioned. Survival of the larvae were observed at 37°C in an incubator. To analyze the susceptibility of the bacterial infections towards gentamicin, survival of the larvae compared with control group implanted only with bone cement. The effect of gentamicin was also measured in terms of S. aureus load in larvae on 2. nd. day. SEM analysis was performed to see the effect of gentamicin on biofilm formation on bone cement. Results. Our experiments established the G. mellonella as an excellent model to screen bone cement with antimicrobial compounds against bacterial infections. The gentamicin bone cement samples showed excellent S. aureus bacterial load reduction after the implantation in G. mellonella model. The bone cement with gentamicin showed better survival of larvae infected with S. aureus compared to control. Finally, the gentamicin also affected the biofilm formation on the bone cement surface with S. aureus. Conclusions. Thus, our work showed G. mellonella is a rapid, cheap economical pre-clinical model to study the bone cement associate bacterial infections as well as screening of the various antimicrobial compounds

Background. Additive manufacturing (AM) has created many new avenues for material and manufacturing innovation. In orthopaedics, metal additive manufacturing is now widely used for production of joint replacements, spinal fusion devices, and cranial maxillofacial reconstruction. Plastic additive manufacturing on the other hand, has mostly been utilized for pre-surgical planning models and surgical cutting guides. The addition of pharmaceuticals to additively manufactured plastics is novel, particularly when done at the raw material level. The purpose of this study was to prove the concept of antibiotic elution from additively manufactured polymeric articles and demonstrate feasibility of application in orthopaedics. Methods. Using patented processes, three heat-stable antibiotics commonly used in orthopaedics were combined with six biocompatible polymers (2 bioresorbable) into filament and powder base materials for fused deposition modeling (FDM) and selective laser sintering (SLS) AM processes. Raw materials of 1%, 2%, and 5% antibiotic concentrations (by mass) were produced as well as a blend of all three antibiotics each at 1% concentration. Thin disks of 25 mm diameter were manufactured of each polymer with each antibiotic at all concentrations. Disks were applied to the center of circular petri dishes inoculated with a bacterium as per a standard zone of inhibition, or Kirby-Bauer disk diffusion tests. After 72 hours incubation, the zone of inhibited bacterial growth was measured. Periprosthetic joint infection (PJI) of the knee was selected as the proof-of-concept application in orthopaedics. A series of tibial inserts mimicking those of a common TKR system were manufactured via SLS using a bioresorbable base material (Figure 1). Three prototype inserts were tested on a knee wear simulator for 333,000 cycles following ISO 14242–1:2014 to approximate 2–4 months of in vivo use between surgeries of a 2-stage procedure for PJI. Gravimetric measurement and visual damage assessment was performed. Results. Bacterial growth was inhibited to a mean diameter of 32.3 mm (FDM) and 42.2 mm (SLS) for nearly all combinations of polymers and concentrations of antibiotics. Prototype tibial inserts experienced an average of 200 mg of wear during testing and demonstrated no evidence of cracking, delamination or significant deformation (Figure 2). Conclusion. Bench-level testing of these novel antibiotic-eluting polymers demonstrates feasibility for their application in orthopaedic medicine. In particular, treatment of stubborn PJI with potential for increased and sustained antibiotic elution, patient-specific cocktailing, and maintenance of knee joint structure and function compared to existing PJI products and practices. Subsequent testing for these novel polymers will determine static and dynamic (wear-induced) antibiotic elution rates. For any figures or tables, please contact the authors directly

The spine is one of the most common sites of bony metastasis, with 80% of prostate, lung, and breast cancers metastasizing to the vertebrae resulting in significant morbidity. Current treatment modalities are systemic chemotherapy, such as Doxorubicin (Dox), administered after resection to prevent cancer recurrence, and systemic antiresorptive medication, such as Zolendronate (Zol), to prevent tumor-induced bone destruction. The large systemic doses required to elicit an adequate effect in the spine often leads to significant side-effects by both drugs, limiting their prolonged use and effectiveness. Recently published work by our lab has shown that biocompatible 3D-printed porous polymer scaffolds are an effective way of delivering Dox locally over a sustained period while inhibiting tumor growth in vitro. Our lab has also generated promising results regarding antitumor properties of Zol in vitro. We aim to develop 3D-printed scaffolds to deliver a combination of Zol and Dox that can potentially allow for a synergistic antitumor activity while preventing concurrent bone loss locally at the site of a tumor, avoiding long systemic exposure to these drugs and decreasing side effects in the clinical setting. The PORO Lay polymer filaments are 3D-printed into 5mm diameter disks, washed with deionized water and loaded with Dox or Zol in aqueous buffer over 7 days. Dox or Zol-containing supernatant was collected daily and the drug release was analyzed over time in a fluorescence plate reader. The polymer-drug (Dox or Zol) release was tested in vitro on prostate and lung cancer cell lines and on prostate- or lung-induced bone metastases cells. Alternatively, direct drug treatment was also carried out on the same cells in vitro. Following treatment, all cells were subject to proliferation assay (MTT and alamar blue), viability assay (LIVE/DEAD), migration assay (Boyden chamber) and invasion assay (3D gel matrix). 3D-printed scaffolds loaded with both Dox and Zol will also be tested on cells. We have established an effective dose (EC50) for prostate and lung cancer cell lines and bone metastases cells with direct treatment with Zol or Dox. We have titrated the drug loading of scaffolds to allow for a release amount of Dox at the EC50 dose over 7 days. In ongoing experiments, we are testing the release of Zol. We have shown Dox releasing scaffolds inhibit cancer cell growth in a 2D culture over 7 days using the above cellular assays and testing the scaffolds with Zol is currently being analyzed. 3D-printed porous polymers like the PORO Lay series of products offer a novel and versatile opportunity for delivery of drugs in future clinical settings. They can decrease systemic exposure of drugs while at the same time concentrating the drugs effect at the site of tumors and consequently inhibit tumor proliferation. Their ability to be loaded with multiple drugs can allow for achieving multiple goals while taking advantage of synergistic effects of different drugs. The ability to 3D-print these polymers can allow for production of custom implants that offer better structural support for bone growth

Aim. Treatment of prosthetic joint infection (PJI) by systemic administration of high doses of long-term antibiotics often proves ineffective, causing severe side effects. Thus, we presented the phage Sb-1, which coding extracellular polymeric substances (EPS) degradation depolymerases, conjugated with rifampicin-loaded liposomes (Lip-RIF@Phage) by bio-orthogonal functionalization strategy to target biofilm (Figure1). Method. Methicillin-resistant Staphylococcus aureus (MRSA) biofilm was grown on porous glass beads for 24 h in vitro. After the biofilm formation, beads were exposed to 0.9% saline, then sonication. Quantitative and qualitative biofilm analyses were performed by colony counting, scanning electron microscopy and isothermal microcalorimetry. A rat model of total knee arthroplasty infected with the bioluminescent MRSA strain was developed as the PJI model to evaluate the efficacy of Lip-RIF@Phage anti-biofilm therapy in vivo, then the creatinine, alanine transaminase, and aspartate transaminase values were evaluated throughout the entire treatment process. Results. After treatment with Lip-RIF@Phage, no bacterial colonies were observed, consistent with findings from scanning electron microscopy. Similarly, isothermal microcalorimetry revealed no detectable heat following Lip-RIF@Phage treatment, aligning with these observations. In vivo experiments demonstrated a significant reduction in biofilm cell load compared to all other tested conditions, with no evidence of systemic toxicity on renal and liver functions attributed to Lip-RIF@Phage. Conclusions. The innovative depolymerase-phagobot nanosystem (Lip-RIF@Phage) exhibits remarkable efficacy in completely eliminating biofilm cells in vitro. It serves as an excellent carrier for antibiotic delivery, enhancing antibiotic penetration through biofilms and improving biofilm eradication efficacy. Furthermore, it enables personalized treatment strategies against biofilm-associated multidrug-resistant (MDR) infections by maximizing the effectiveness of any remaining sensitive antibiotics. For any tables or figures, please contact the authors directly

Conventional fracture courses utilise prefabricated sawbones that are not realistic or patient specific. The aim of this study is to determine the feasibility of creating 3D fracture models and utilising them in fracture courses to teach surgical technique. We selected an AO type 2R3C2 fracture that underwent open reduction internal fixation. De-identified CT scan images were converted to a stereolithography (STL) format. This was then processed using Computer Aided Design (CAD) to create a virtual 3D model. The model was 3D printed using a combination of standard thermoplastic polymer (STP) and a porous filler to create a realistic cortical and cancellous bone. A case-based sawbone workshop was organised for residents, unaccredited registrars, and orthopaedic trainees comparing the fracture model with a prefabricated T-split distal radius fracture. Pre-operative images aided discussion of fixation, and post-operative x-rays allowed comparison between the participants fixation. Participants were provided with identical reduction tools. We created a questionnaire for participants to rate their satisfaction and experience using a Likert scale. The 3D printed fracture model aided understanding and appreciation of the fracture pattern and key fragments amongst residents and unaccredited trainees. Real case-based models provided a superior learning experience and environment to aid teaching. The generic sawbone provided easier drilling and inserting of screws. Preliminary results show that the cost of 3D printing can be comparable to generic sawbones. It is feasible to create a fracture model with a real bone feel. Further research and development is required to determine the optimum material to use for a more realistic feel. The use of 3D printed fracture models is feasible and provides an alternative to generic sawbone fracture models in providing surgical training to residents

Tissue engineering by self-assembly is a technique that consists of growing cells on surfaces made of thermoresponsive polymers, that allow the production of contiguous cell sheets by simply lowering the temperature below the polymer's low critical solution temperature. In this approach cell-cell junctions and deposited extracellular matrix (ECM) remain intact, which provides a better cell localisation at the site of injury. However, these systems lack the possibility to fabricate multi-layered and three-dimensional cell sheets that would better recapitulate native tissues. Moreover, the fabrication of ECM-rich cell sheets would be highly desirable. This limitation could be overcome by inducing macromolecular crowding (MMC) conditions. Herein we venture to fabricate electrospun thermoresponsive nanofibres to sustain the growth and detachment of ECM-rich tissue substitutes in the presence of a MMC microenvironment. A copolymer of 85% poly-N-isopropylacrylamide and 15% N-tert-butylacrylamide (pNIPAAm/NTBA) were used for all experiments. To create aligned nanofibers, the polymer was electrospun and collected on a mandrel rotating at 2000 rpm. Human adipose derived stem cells (hADSC) were treated with media containing macromolecular crowders to enhance matrix deposition. Cell viability and morphology were assessed, and immunocytochemistry was conducted in order to estimate matrix deposition and composition. Adipogenic, osteogenic and chondrogenic assays were performed both with and without the presence of MMC. Non-invasive cell detachment was enabled by decreasing the temperature of culture to 10 °C for 20 minutes. The electrospinning process resulted in the production of pNIPAm/NTBA fibres in the diameter range from 1 to 2 µm and an overall alignment of 80%. Cell viability, proliferation and metabolic activity revealed that hADSCs were able to grow on the thermoresponsive scaffold. The cells were able to detach as an intact cell sheet in presence of MMC. Moreover, it was demonstated that MMC, by a volume extrusion effect, enhances Collagen type I deposition, which is one of the main components of the ECM. Histological analysis revealed that in the presence of MMC the cells were able to self-assembled into three dimensional multi-layers. The cells were able to differentiate towards the osteogenic and adipogenic lineage in the presence of MMC. Interestingly we were able to fabricate three-dimensional chondrogenic cell sheet both with and without MMC. Collectively the pNIPAm/NTBA thermoresponsive fibres were able to sustain the growth and the detachment of ECM-rich multi-layered cell sheets. The pNIPAm/NTBA fibres were able to successfully sustain growth and detachment of ECM-rich tissue equivalents. We believe that replacement, repair and restoration of tissue function can be accomplished best using cells that create their own tissue-specific extracellular matrix with a precision and stoichiometric efficiency still unmatched by man-made devices

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

Aim. To develop a new system for antibacterial coating of joint prosthesis and osteosynthesis material. The new coating system was designed to release gentamicin immediately after insertion to eradicate surgical contamination. Method. Steel implants (2×15mm) were coated with a solid nanocomposite xerogel made from silica and the dendritic polymer, hyperbranched polyethyleneimine. The xerogel was anchored inside a porous surface made by pre-coating with titanium microspheres. Finally, gentamicin was encapsulated in the xerogel, i.e. no chemical binding. A total of 50 µg gentamicin was captured into each implant. The efficacy of the new coating was evaluated in a porcine model of implant associated osteomyelitis. In total, 30 female pigs were randomized into 3 study groups (n=10). Group A; plain implants + saline, Group B; plain implants + 10. 4. CFU of Staphylococcus aureus, and Group C; coated implants + 10. 4. CFU of S. aureus. Implant + inoculum was placed into a pre-drilled implant cavity of the right tibia and the pig was euthanized 5 days afterwards. Postmortem microbiology and pathology were performed. Two additional pigs were used in a pharmacokinetic study where microdialysis (MD) catheters were placed alongside coated implants. Extracellular fluid was sampled regularly for 24 hours from the MD catheters and analyzed for gentamicin content. Results. Within Groups A and C, all implants were found sterile by sonication and bacteria could not be identified within the surrounding bone tissue. In contrast, all Group B animals had S. aureus positive implant and tissue microbiology. Macroscopic and microscopic pathological examinations confirmed that Group A and C animals were complete identic, i.e. no pus around implants and only minor peri-implant inflammation related to insertion of implants per se. All Group B animals had pus around their implants and a massive peri-implant inflammatory response dominated by neutrophil granulocytes. Maximum gentamicin release (35 µg /mL) was measured in the first obtained MD sample, i.e. after 30 min, and the concentration stayed above the MIC level for the used S. aureus strain for 8 hours. Conclusions. The new xerogel coating prevented development of osteomyelitis. Prevention was due to a fast gentamicin release immediately following insertion and antimicrobial active concentrations were detectable several hours after implantation. This means that the critical time point of most relevant surgical procedures potentially could be protected by the novel coating. The new coating will be investigated on larger scale implants and full-size prosthesis in the future

Introduction. Total hip replacement with metal-on-polymer (MoP) hip prostheses is a successful treatment for late-stage osteoarthritis. However, the wear debris generated from the polymer acetabular liners remains a problem as it can be associated with osteolysis and aseptic loosening of the implant. This has led to the investigation of more wear resistant polymers in orthopaedics. Cross-linked polyethylene (XLPE) is now the gold-standard acetabular liner material. However, we asked if carbon fibre reinforced polyether ether ketone (CFR-PEEK) might be a lower wear material. In addition, we sought to understand the influence of contact stress on the wear of both XLPE and CFR-PEEK as this has not previously been reported. Materials and Methods. A 50-station circularly translating pin-on-disc (SuperCTPOD) machine was used to wear test both XLPE and CFR-PEEK pins against cobalt chromium (CoCr) discs to investigate the influence of contact stress on their wear rates. Fifty XLPE and 50 CFR-PEEK pins were articulated against CoCr discs. The pins, 9 mm in outer diameter and 12 mm in height, were drilled with different diameter holes to generate different sized annuli and thus, different contact areas. The pins were tested at 1.10, 1.38, 1.61, 2.00 and 5.30 MPa, which are typical contact stresses observed in the natural hip joint. An additional pin for every test group was used as a control to track the lubricant uptake. The discs were polished to 0.015 μm Sa prior to testing. The test stations contained 16 ml of diluted newborn calf serum (protein concentration: 22 g/L). Wear was measured gravimetrically with a balance (resolution: 10 μm) every 500,000 cycles. A standardised cleaning and weighing protocol was followed. Results and Discussion. The wear rates for the XLPE pins were calculated as 1.05, 0.90, 0.77, 0.48 and 0.28 mg/million cycles for the different pin stress groups respectively. The wear rates decreased with increasing contact stress, which was similar to what was observed for ultra-high molecular weight polyethylene (UHMWPE). The change in weight of the discs was insignificant (p-value:0.85). For the CFR-PEEK pin groups, the wear rates were calculated as 0.56, 0.65, 0.61, 0.58 and 0.65 mg/million cycles respectively. The difference between the wear rates was insignificant (p-value: 0.92). However, the weight of the discs decreased significantly (p-value: 0.00). At 1.11 MPa and taking data for UHMWPE tested in the same way, comparison of the three polymers showed that CFR-PEEK produced the lowest wear against CoCr. Although the wear rates for CFR-PEEK were found to be the lowest, the decrease in weight of the CoCr discs articulated against CFR-PEEK was indicative of metallic wear. Conclusion. CFR-PEEK should not be used against orthopaedic metals. XLPE articulating against CoCr was found to be the optimum combination, producing low wear without causing weight change from the counterface, under varying contact stresses

Contemporary crosslinked polymers didn't just happen. The material was, has, and continues to be studied more than any other bearing surface material used in the total hip and total knee replacement construct. Historical failures and successes provided the information needed to make it the success that it is today as we approach the end of the second decade of extensive use. Recognition that wear particles, not cement, was the major cause of osteolysis was important. Next, understanding that oxidation from free radical formation was deleterious to wear resistant polyethylene was understood and finally, that crosslinking was responsible for magnitude increases in wear resistance. Although manufacturers have developed multiple processes to develop their crosslinked polymers (gamma and e beam radiation, melting and annealing, and most recently the addition of antioxidants) there are excellent 10-year results demonstrating head penetration rates (indicative of wear and creep) in the 0.02 to 0.04 mm/year range for many materials with minimal if any detection of osteolysis on radiographs and close to 0% revised for wear at 10+ years. Are there any cautions? Recently, at 10- to 15-year follow up, some clinically insignificant osteolysis has been noted in one study and in that same study, 36 mm heads had twice the volumetric wear as 32 mm heads, but it was still a relatively low volume compared to the previous generation polyethylenes. We need further follow up, but at two decades of use, crosslinked polymers have dramatically reduced the osteolysis problem