Aim. Fungal periprosthetic joint infections are difficult to treat and often associated with a limited outcome for patients. Candida species account for approximately 90% of all fungal infections. In vivo biofilm models play major role to study biofilm development, morphology, and regulatory molecules for bacteria. However, in vivo modeling of biofilm-associated fungi models are very rare. Furthermore, due to ethical restrictions, mammalian models are replaced with other alternative models in basic research. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections with bacteria. This model organism was not used for fungi biofilm infection yet. Thus, we aimed to establish G. mellonella as in vivo model to study fungal implant infections using Candida albicans as model organism and to test anti-fungal medication. Method. Titanium and Stainless steel K-wires were cut into small pieces with size of 4mm. For the infection process, implants were pre-incubated in specified fungal growth culture Candida albicans at 1×10. 7. 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. To analyze the susceptibility of the implant-associated fungal infections towards anti fungal compounds, the larvae were treated with amphotericin B, fluconazole and voriconazole after 24h of implantation. The effect of anti-fungal compounds was measured in terms of survival observation for 5 days and fungal load in larvae on 2. nd. day. To reveal the fungal biofilm formation on implant, the implants were removed on day 3 and processed for SEM analysis. Results. Pre-incubated K-wire caused the Candida infection and observed the death of the larvae. The treatment with antifungal compounds recovered the larvae from the implant-infection, except in case of Voriconazole. However, the recovery with treatment of anti fungal compounds was not effective as the larvae with planktonic infection, which highlights typical biofilm phenotype. Further, the treatment with anti-fungal compounds with Amphotericin B and Fluconazole reduced the fungal load in larvae tissue. The SEM analysis revealed the formation fungal biofilm with hyphae and spores associated with larvae tissue on implant surface. Conclusions. The results from survival analysis, antifungal treatment and SEM analysis are very promising to use of G. mellonella as in vivo model to study fungal infections on implanted materials. Our study highlights the use of G. mellonella larvae as alternative in vivo model to study implant-associated fungal infections that reduces the use of the higher mammals

3D printing and Bioprinting technologies are becoming increasingly popular in surgery to provide a solution for the regeneration of healthy tissues. The aim of our project is the regeneration of articular cartilage via bioprinting means, to manage isolated chondral defects. Chrondrogenic hydrogel (chondrogel: GelMa + TGF-b3 and BMP6) was prepared and sterilised in our lab following our standard protocols. Human adipose-derived mesenchymal stem cells were harvested from the infrapatellar fat pad of patients undergoing total knee joint replacements and incorporated in the hydrogel according to our published protocols. The chondrogenic properties of the chondrogel have been tested (histology, immunohistochemistry, PCR, immunofluorescence, gene analysis and 2. nd. harmonic generation microscopy) in vitro and in an ex-vivo model of human articular defect and compared with standard culture systems where the growth factors are added to the media at repeated intervals. The in-vitro analysis showed that the formation of hyaline cartilage pellet was comparable between the two strategies, with a similar metabolic activity of the cells. These results have been confirmed in the ex-vivo model: hyaline-like cartilage was observed within the chondral defect in both the chondrogel group and the control group after 28 days in culture. The use of bioprinting techniques in vivo requires the ability of stem cells to access growth factors directly in the environment they are in, as opposed to in vitro techniques where these factors are provided externally at recurrent intervals. This study showed the successful strategy of incorporating chondrogenic growth factors for the formation of hyaline-like cartilage in vitro and in an ex-vivo model of chondral loss. The incorporation of chondrogenic growth factors in a hydrogel is a possible strategy for articular cartilage regeneration

Aim. To provide proof of concept in an in vivo animal model for the prevention of prosthetic joint infection prevention using electric fields along with conventional antibiotic prophylaxis. Corresponding Author: Marti Bernaus. Method. First, we standardized the animal model to simulate implant contamination during the surgical procedure. We then implanted cobalt-chrome prostheses adapted to both knees of two New Zealand White rabbits, under standard aseptic measures and antibiotic prophylaxis with cefazolin. Prior to implantation, we immersed the prostheses in a 0.3 McFarland inoculum of S. aureus (ATCC 25923) for 30 seconds. In the first animal (control), the joint was directly closed after washing with saline. In the second animal (case), both prostheses were treated with electric current pulses for 30 seconds, washed with saline, and the joint was closed. After 72 hours, both animals were reoperated for the collection of periprosthetic tissue and bone samples, and prosthesis removal. In all samples, we performed quantitative cultures prior to vortexing and sonication, as well as prolonged cultures of the sonication broth. We confirmed the absence of contamination by identification with MALDI-TOF (VITEK-MS) and automated antibiotic susceptibility testing of the isolated colonies (VITEK-2). Results. In the “control” animal, we isolated S. aureus in all studied samples. The bacterial count expressed as log10 (cfu/cm2) in the prostheses of the right and left legs was 9.38 and 8.86, respectively. The bacterial count expressed as log10 (cfu/mL) in bone and periprosthetic tissue biopsies was 2.70 and 2.72 in the right leg and 3.24 and 3.87 in the left leg, respectively. In the “case” animal, where an electric field was applied to the implant after placement in addition to cefazolin prophylaxis, all samples (prosthesis, bone, and periprosthetic tissue) were negative, and no isolation of the inoculated strain of S. aureus was obtained after incubation of the sonication broth for 14 days. Conclusions. This in vivo model suggests the potential effectiveness of applying an electric field to a prosthetic implant in combination with cefazolin for the prevention of PJI development, after exposure of the implant to an inoculum of S. aureus (ATCC 25923). Our findings need to be confirmed using a larger sample size

Aim. In vivo biofilm models play major role to study biofilm development, morphology, and regulatory molecules involve in biofilm. Due to ethical restrictions, the use mammalian models are replaced with other alternative models in basic research. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections. This model organism is easy to handle, cheap and ethical restriction free and could be used for the high through put screening of antimicrobial compounds to treat biofilm. To promote the use of this model in basic research we aimed to validate this based on the typical biofilm features such as less susceptible to the antibiotics, complexity of the biofilm structure and gene expression profile of biofilms. Method. G. mellonella larvae are maintained at 30oC on artificial diet in an incubator. Titanium and Stainless steel K-wires were cut into small pieces with size of 4mm. After sterilization with 100% alcohol, these K-wires were pre-incubated in S. aureus bacterial suspension (5×10. 6. CFU/ml) for 30 min, washed in PBS and implanted inside the larva after with help of scalpel. The larvae were incubated at 37. o. C for two day for the survival analysis. To analyze the less susceptibility of the biofilms towards antibiotics, the larvae were treated with gentamicin and compared survival with planktonic infection in G. mellonella. To reveal the complex structure of biofilm, the implants were removed and processed for the MALDI analysis. Whole genome-based transcriptome of biofilm was performed to explore the changes in transcriptional landscapes. Results. The results are very promising to validate the use of G. mellonella as in vivo model to study the biofilm formation on implanted materials. The gentamicin treatment could rescue the larvae from the planktonic infection, but not from the biofilm infection on the implants. Further, the MALDI analysis could reveal the complex structure and components of S. aureus biofilm formed on the implant inside the larvae. Finally, the transcriptomic analysis revealed the gene expression changes that can be compared to normal biofilm expression profile. Conclusions. Further, comparison of these results with other in vivo models such as rat and mouse as well as acute and chronic clinical samples from patients with implant-associated bone infections could validate and relevant use of this model to study S. aureus biofilm infections

Introduction. Recent technological advancements have led to the introduction of robotic-assisted total knee arthroplasty to improve the accuracy and precision of bony resections and implant position. However, the in vivo accuracy is not widely reported. The primary objective of this study is to determine the accuracy and precision of a cut block positioning robotic arm. Method. Seventy-seven patients underwent total knee arthroplasty with various workflows and alignment targets by three arthroplasty-trained surgeons with previous experience using the ROSA® Knee System. Accuracy and precision were determined by measuring the difference between various workflow time points, including the final pre-operative plan, validated resection angle, and post-operative radiographs. The mean difference between the measurements determined accuracy, and the standard deviation represented precision. Results. The accuracy and precision for all angles comparing the final planned resection and validated resection angles was 0.90° ± 0.76°. The proportion within 3° ranged from 97.9% to 100%. The accuracy and precision for all angles comparing the final intra- operative plan and post-operative radiographs was 1.95 ± 1.48°. The proportion of patients within 3° was 93.2%, 95.3%, 96.6%, and 71.4% for the distal femur, proximal tibia, femoral flexion, and tibial slope angles when the final intra-operative plan was compared to post-operative radiographs. No patients had a postoperative complication requiring revision at the final follow-up. Conclusions. This study demonstrates that the ROSA Knee System has accurate and precise coronal plane resections with few outliers. However, the tibial slope demonstrated decreased accuracy and precision were measured on post-operative short-leg lateral radiographs with this platform

Despite the increasing availability of bone grafting materials, the regeneration of large bone defects remains a challenge. Especially infection prevention while fostering regeneration is a crucial issue. Therefore, loading of grafting material with antibiotics for direct delivery to the site of need is desired. This study evaluates the concept of local delivery using in vitro and in vivo investigations. We aim at verifying safety and reliability of a perioperative enrichment procedure of demineralized bone matrix (DBM) with gentamicin. DBM (DBMputty, DIZG, Germany) was mixed with antibiotic using a syringe with an integrated mixing propeller (Medmix Systems, Switzerland). Gentamicin, as powder or solution, was mixed with DBM at different concentrations (25 −100 mg/g DBM), release and cytotoxicity was analyzed. For in vivo analysis, sterile drill hole defects (diameter: 6 mm, depth: 15 mm) were created in diaphyseal and metaphyseal bones of sheep (Pobloth et al. 2016). Defects (6 – 8 per group and time point) were filled with DBM or DBM enriched with gentamicin (50 mg/g DBM) or left untreated. After three and nine weeks, defect regeneration was analyzed by µCT and histology. The release experiments revealed a burst release of gentamicin from DBM independent of the used amount, the sampling strategy, or the formulation (powder or solution). Gentamicin was almost completely released after three days in all set-ups. Eluates showed an antimicrobial activity against S. aureus over at least three days. Eluates had no negative effect on viability and alkaline phosphatase activity of osteoblast-like cells (partially published Bormann et al. 2014). µCT and histology of the drill hole defects revealed a reduced bone formation with gentamicin loaded DBM. After nine weeks significantly less mineralized tissue was detectable in metaphyseal defects of the gentamicin group. Histological evaluation revealed new bone formation starting at the edges of the drill holes and growing into the center over time. The amount of DBM decreased over time due to the active removal by osteoclasts while osteoblasts formed new bone. Using this mixing procedure, loading of DBM was fast, reliable and possible during surgical setting. In vitro experiments revealed a burst and almost complete release after three days, antimicrobial activity and good biocompatibility of the eluates. Gentamicin/DBM concentration was in the range of clinically used antibiotic-loaded-cement for prophylaxis and treatment in joint replacement (Jiranek et al. 2006). The delayed healing seen in vivo was unexpected due to the good biocompatibility found in vitro. A reduced healing was also seen in spinal fusion where DBM was mixed with vancomycin (Shields et al. 2017), whereas DBM with gentamicin or DBM/bioactive glass with tobramycin had no negative effect on osteoinductivity or femur defect healing, respectively (Lewis et al. 2010, Shields et al. 2016). In conclusion, loading of DBM with gentamicin showed a proper antibiotic delivery over several days, covering the critical phase shortly after surgery. Due to the faster and complete release of the antibiotic compared to antibiotic loaded cement, the amount of antibiotic should be much lower in the DBM compared to cement

Introduction: The mechanobiology and response of bone formation to strain under physiological loading is well established, however investigation into exceedingly soft scaffolds relative to cancellous bone is limited. In this study we designed and 3D printed mechanically-optimised low-stiffness implants, targeting specific strain ranges inducing bone formation and assessed their biological performance in a pre-clinical in vivo load-bearing tibial tuberosity advancement (TTA) model. The TTA model provides an attractive pre-clinical framework to investigate implant osseointegration within an uneven loading environment due to the dominating patellar tendon force. A knee finite element model from ovine CT data was developed to determine physiological target strains from simulated TTA surgery. We 3D printed low-stiffness Ti wedge osteotomy implants with homogeneous stiffness of 0.8 GPa (Ti1), 0.6 GPa (Ti2) and a locally-optimised design with a 0.3 GPa cortex and soft 0.1 GPa core (Ti3), for implantation in a 12-week ovine tibial advancement osteotomy (9mm). We quantitatively assessed bone fusion, bone area, mineral apposition rate and bone formation rate. Optimised Ti3 implants exhibited evenly high strains throughout, despite uneven wedge osteotomy loading. We demonstrated that higher strains above 3.75%, led to greater bone formation. Histomorphometry showed uniform bone ingrowthin optimised Ti3 compared to homogeneous designs (Ti1 and Ti2), and greater bone-implant contact. The greatest bone formation scores were seen in Ti3, followed by Ti2 and Ti1. Results from our study indicate lower stiffness and higher strain ranges than normally achieved in Ti scaffolds stimulate early bone formation. By accounting for loading environments through rational design, implants can be optimised to improve uniform osseointegration. Design and 3D printing of exceedingly soft titanium orthopaedic implants enhance strain induced bone formation and have significant importance in future implant design for knee, hip arthroplasty and treatment of large load-bearing bone defects

Introduction. Friction between head and cup is a primary factor for survival of total hip joint replacement (THR) and its gliding surfaces. In up to 40% of all revisions, the cup or inlay must be replaced as result of friction-induced wear [1]. Aim of the study was to measure the friction-induced temperature increase in vivo in THR and to identify possible individual parameters of influence. Methods. For the in vivo measurement, an instrumented implant with an Al. 2. O. 3. /XPE-pairing and an integrated temperature sensor was used [Fig. 1] [2]. Ten patients were provided with such an instrumented implant. Up to now, long time measurements were performed on six of these patients (Ø63y, Ø89kg). During these measurements, the subjects walked Ø60min on a treadmill with 4km/h. The investigation was performed Ø61 (43–70) months post operatively. Short time (Ø3min) in vivo load measurements during walking on treadmill were already available from the other four patients. These data were used to calculate the peak temperatures after 60mins of walking by using a model, based on the long time measurements. Results. The peak values of the friction-induced temperature increase were achieved in vivo after 30min (H7R) to 70min (H2R), with peak temperatures between 1.5°C (H6R) to 4.8°C (H7R) [Fig. 2]. These maximum values were similar to those already observed in other patients [3]. The in vivo measured peak values of the friction-induced temperature increase after long time walking on a treadmill with respect to the implant orientation are shown in Fig. 3 as points and the calculated peak values as circles. First analyses have shown that the individual implant orientations seem to have an influence [Fig. 3] on the friction-induced increase of the joint temperature during walking, but also the patient's age. Discussion. The gliding partners and joint lubrication directly influence friction in artificial hip joint replacements and thus the friction- induced temperature increase. Analyses of the in vivo acting joint friction during walking have shown that there is an increase in friction over the course of each gait cycle after contralateral toe off [4]. This can be explained by a decrease in the lubricating film thickness due to the pressing out of the synovia from the joint space. During load reduction of the joint in the swing phase, the fluids are transported back into the joint space. Thus, the level of joint friction at the beginning of the next gait cycle depends on the return transport of the synovia. The influence of the sum anteversion angle (ΣAV) on friction-induced temperature increase (Fig. 3) can therefore be explained mechanically: The ΣAV determines the functional joint roofing and the position of the load-transferring zone into the joint socket. The larger the ΣAV, the more it shifts towards the edge of the socket, and the shorter the path for the return transport of the synovium

The purpose of this study was to examine the influence of weight-bearing on the measurement of in vivo wear of total knee replacements using model-based RSA at 1 and 2 years following surgery. Model-based RSA radiographs were collected for 106 patients who underwent primary TKR at a single institution. Supine RSA radiographs were obtained post-operatively and at 6-, 12-, and 24-months. Standing (weight-bearing) RSA radiographs were obtained at 12-months (n=45) and 24-months (n=48). All patients received the same knee design with a fixed, conventional PE insert of either a cruciate retaining or posterior stabilized design. Ethics approval for this study was obtained. In order to assess in vivo wear, a highly accurate 3-dimensional virtual model of each in vivo TKA was developed. Coordinate data from RSA radiographs (mbRSA v3.41, RSACore) were applied to digital implant models to reconstruct each patient's replaced knee joint in a virtual environment (Geomagic Studio, 3D Systems). Wear was assessed volumetrically (digital model overlap) on medial and lateral condyles separately, across each follow-up. Annual rate of wear was calculated for each patient as the slope of the linear best fit between wear and time-point. The influence of weight-bearing was assessed as the difference in annual wear rate between standing and supine exams. Age, BMI, and Oxford-12 knee improvement were measured against wear rates to determine correlations. Weight bearing wear measurement was most consistent and prevalent in the medial condyle with 35% negative wear rates for the lateral condyle. For the medial condyle, standing exams revealed higher mean wear rates at 1 and 2 years, supine, 16.3 mm3/yr (SD: 27.8) and 11.2 mm3/yr (SD: 18.5) versus standing, 51.3 mm3/yr (SD: 55.9) and 32.7 mm3/yr (SD: 31.7). The addition of weight-bearing increased the measured volume of wear for 78% of patients at 1 year (Avg: 32.4 mm3/yr) and 71% of patients at 2 years (Avg: 48.9 mm3/yr). There were no significant (95% CI) correlations between patient demographics and wear rates. Volumetric, weight-bearing wear measurement of TKR using model-based RSA determined an average of 33 mm3/yr at 2 years post-surgery for a modern, non-cross-linked polyethylene bearing. This value is comparable to wear rates obtained from retrieved TKRs. Weight-bearing exams produced better wear data with fewer negative wear rates and reduced variance. Limitations of this study include: supine patient imaging performed at post-op, no knee flexion performed, unknown patient activity level, and inability to distinguish wear from plastic creep or deformation under load. Strengths of this study include: large sample size of a single TKR system, linear regression of wear measurements and no requirement for implanted RSA beads with this method. Based on these results, in vivo volumetric wear of total knee replacement polyethylene can be reliably measured using model-based RSA and weight-bearing examinations in the short- to mid–term. Further work is needed to validate the accuracy of the measurements in vivo

Polyethylene wear represents a significant risk factor for the long-term success of knee arthroplasty [1]. This work aimed to develop and in vivo validate an automated algorithm for accurate and precise AI based wear measurement in knee arthroplasty using clinical AP radiographs for scientifically meaningful multi-centre studies. Twenty postoperative radiographs (knee joint AP in standing position) after knee arthroplasty were analysed using the novel algorithm. A convolutional neural network-based segmentation is used to localize the implant components on the X-Ray, and a 2D-3D registration of the CAD implant models precisely calculates the three-dimensional position and orientation of the implants in the joint at the time of acquisition. From this, the minimal distance between the involved implant components is determined, and its postoperative change over time enables the determination of wear in the radiographs. The measured minimum inlay height of 335 unloaded inlays excluding the weight-induced deformation, served as ground truth for validation and was compared to the algorithmically calculated component distances from 20 radiographs. With an average weight of 94 kg in the studied TKA patient cohort, it was determined that an average inlay height of 6.160 mm is expected in the patient. Based on the radiographs, the algorithm calculated a minimum component distance of 6.158 mm (SD = 81 µm), which deviated by 2 µm in comparison to the expected inlay height. An automated method was presented that allows accurate and precise determination of the inlay height and subsequently the wear in knee arthroplasty based on a clinical radiograph and the CAD models. Precision and accuracy are comparable to the current gold standard RSA [2], but without relying on special radiographic setups. The developed method can therefore be used to objectively investigate novel implant materials with meaningful clinical cohorts, thus improving the quality of patient care

HXLPE acetabular liners were introduced to reduce wear-related complications in THA. However, post-irradiation thermal free radical stabilization can compromise mechanical properties, leave oxidation-prone residual free radicals, or both. Reports of mechanical failure of HXLPE acetabular liner rims raise concerns about thermal free radical stabilization and in vivo oxidization on implant properties. The purpose of this study is to explore the differences in the mechanical, physical and chemical properties of HXLPE acetabular liner rims after extended time in vivo between liners manufactured with different thermal free radical stabilization techniques. Remelted, single annealed and sequentially annealed retrieved HXLPE acetabular liners with in vivo times greater than 4.5 years were obtained from our implant retrieval laboratory. All retrieved liners underwent an identical sanitation and storage protocol. For mechanical testing, a total of 55 explants and 13 control liners were tested. Explant in vivo time ranged from 4.6 – 14 years and ex vivo time ranged from 0 – 11.6 years. Rim mechanical properties were tested by microindentation hardness testing using a Micromet II Vickers microhardness tester following ASTM standards. A subset of 16 explants with ex vivo time under one year along with five control liners were assessed for oxidation by FTIR, crystallinity by Raman spectroscopy, and evidence of microcracking by SEM. No significant difference in in vivo or ex vivo was found between thermal stabilization groups in either set of explants studied. In the mechanically tested explants, there was no significant correlation between in vivo time and Vickers hardness in any thermal stabilization group. A significant correlation was found between ex vivo time and hardness in remelted liners (r=.520, p = .011), but not in either annealed cohort. ANCOVA with ex vivo time as a covariate found a significant difference in hardness between the thermal free radical stabilization groups (p 0.1) was found in retrieved remelted (25%), single annealed (100%) and sequentially annealed (75%) liner rims. Crystallinity was increased in the subsurface region relative to control liners for both annealed, but not remelted, liner rims. Hardness was increased in oxidized rims for both annealed cohorts but not in the remelted cohort. Microcracking was only found along the surface of one unoxidized remelted liner rim. Mechanical properties were reduced at baseline and worsened after in vivo time for remelted HXLPE liner rims. Rim oxidation was detected in all groups. Oxidation was associated with increased crystallinity and hardness in annealed cohorts, but not remelted liners. Increased crystallinity and oxidation do not appear to be directly causing the worsened mechanical behavior of remelted HXLPE liner rims after extended in vivo time

Background. Although early TKA designs were symmetrical, during the past two decades TKA have been designed to include asymmetry, pertaining to either the trochlear groove, femoral condylar shapes or the tibial component. More recently, a new TKA was designed to include symmetry in all areas of the design, in the hopes of reducing design and inventory costs. Objective. The objective of this study was to determine the in vivo kinematics for subjects implanted with this symmetrical TKA during a weight-bearing deep knee bend activity. Methods. In vivo deep knee bend (DKB) kinematics for 21 subjects implanted with symmetrical posterior cruciate sacrificing (PCS) fixed bearing TKA were obtained using fluoroscopy. A 3D-to-2D registration technique was used to determine each subjects anteroposterior translation of lateral (LAP) and medial (MAP) femoral condyles and tibiofemoral axial rotation and their weight-bearing knee flexion. Results. During the DKB, the average maximum weight-bearing flexion was 111.7° ± 13.3°. On average, from full extension to maximum knee flexion, subjects experienced 2.5 mm ± 2.0 mm femoral rollback on lateral condyle −2.5 mm ± 2.2 mm of medial condyle motion in the anterior direction (Figure 1). This medial condyle motion was consistent for the majority of the subjects with the lateral condyle exhibiting rollback from 0° to 60° of flexion and then an average anterior slide of 0.3 mm from 60° to 90° of flexion. On average, the subjects in this study experienced 6.6° ± 3.3° of axial rotation, with most of rotation occurring in early flexion, averaging 4.9° (Figure 2). Discussion. Although subjects in this study were implanted with a symmetrical TKA, they did experience femoral rollback of the lateral condyle and positive axial rotation. Both of these kinematic parameters were normal-like in pattern, compared to the normal knee in early flexion, but in deeper flexion the pattern of motion varied from the normal knee. Also, the magnitude of posterior femoral rollback and axial rotation revealed similarities to previous fluoroscopy studies on subjects implanted with an asymmetrical TKA design. This was only a single surgeon study, so it is unclear if the results are TKA or surgeon influenced. Therefore, it is proposed that more patients be analyzed having this TKA implanted by other surgeons. For any figures or tables, please contact the authors directly

Introduction. HXLPE acetabular liners were introduced to reduce wear-related complications in THA. However, post-irradiation thermal free radical stabilization can compromise mechanical properties, leave oxidation-prone residual free radicals, or both. Reports of mechanical failure of HXLPE acetabular liner rims raise concerns about thermal free radical stabilization and in vivo oxidization on implant properties. The purpose of this study is to explore the differences in the mechanical, physical and chemical properties of HXLPE acetabular liner rims after extended time in vivo between liners manufactured with different thermal free radical stabilization techniques. Material and Methods. Remelted, single annealed and sequentially annealed retrieved HXLPE acetabular liners with in vivo times greater than 4.5 years were obtained from our implant retrieval laboratory. All retrieved liners underwent an identical sanitation and storage protocol. For mechanical testing, a total of 55 explants and 13 control liners were tested. Explant in vivo time ranged from 4.6 – 14.0 years and ex vivo time ranged from 0 – 11.6 years. Rim mechanical properties were tested by microindentation hardness testing using a Micromet II Vickers microhardness tester following ASTM standards. A subset of 16 explants with ex vivo time under one year along with five control liners were assessed for oxidation by FTIR, crystallinity by Raman spectroscopy, and evidence of microcracking by SEM. Results. No significant difference in in vivo or ex vivo time was found between thermal stabilization groups in either set of explants studied. In the mechanically tested explants, there was no significant correlation between in vivo time and Vickers hardness in any thermal stabilization group. A significant correlation was found between ex vivo time and hardness in remelted liners (r=.520, p=.011), but not in either annealed cohort. ANCOVA with ex vivo time as a covariate found a significant difference in hardness between the thermal free radical stabilization groups (p<.0005, η. 2. = 0.322). Post hoc analysis revealed hardness was significantly lower in the retrieved remelted group compared to both the single annealed (p=.001) and sequentially annealed (p<.0005) cohorts. Hardness was significantly higher in the retrieved remelted liners compared to controls (p=.007), with no different in either annealed cohort. Detectable subsurface oxidation (OI > 0.1) was found in retrieved remelted (25%), single annealed (100%) and sequentially annealed (75%) liner rims. Crystallinity was increased in the subsurface region relative to control liners for both annealed, but not remelted, liner rims. Hardness was increased in oxidized rims for both annealed cohorts but not in the remelted cohort. Microcracking was only found along the surface of one unoxidized remelted liner rim. Conclusion. Mechanical properties were reduced at baseline and worsened after in vivo time for remelted HXLPE liner rims. Rim oxidation was detected in all groups. Oxidation was associated with increased crystallinity and hardness in annealed cohorts, but not remelted liners. Increased crystallinity and oxidation do not appear to be directly causing the worsened mechanical behavior of remelted HXLPE liner rims after extended in vivo time. For any figures or tables, please contact authors directly

Purpose. The purpose of this study was to examine the influence of weight-bearing on the measurement of in vivo wear of total knee replacements using model-based RSA at 1 and 2 years following surgery. Methods. Model-based RSA radiographs were collected for 106 patients who underwent primary TKR at a single institution. Supine RSA radiographs were obtained post-operatively and at 6-, 12-, and 24-months. Standing (weight-bearing) RSA radiographs were obtained at 12-months (n=45) and 24-months (n=48). All patients received the same knee design with a fixed, conventional PE insert of either a cruciate retaining or posterior stabilized design. Ethics approval for this study was obtained. In order to assess in vivo wear, a highly accurate 3-dimensional virtual model of each in vivoTKA was developed. Coordinate data from RSA radiographs (mbRSA v3.41, RSACore) were applied to digital implant models to reconstruct each patient's replaced knee joint in a virtual environment (Geomagic Studio, 3D Systems). Wear was assessed volumetrically (digital model overlap) on medial and lateral condyles separately, across each follow-up. Annual rate of wear was calculated for each patient as the slope of the linear best fit between wear and time-point. The influence of weight-bearing was assessed as the difference in annual wear rate between standing and supine exams. Age, BMI, and Oxford-12 knee improvement were measured against wear rates to determine correlations. Results. Weight bearing wear measurement was most consistent and prevalent in the medial condyle with 0–4% of calculated wear rates being negative compared to 29–39% negative wear rates for the lateral condyle. For the medial condyle, standing exams revealed higher mean wear rates at 1 and 2 years; supine, 16.3 mm. 3. /yr (SD: 27.8) and 11.2 mm. 3. /yr (SD: 18.5) versus standing, 51.3 mm. 3. /yr (SD: 55.9) and 32.7 mm. 3. /yr (SD: 31.7). The addition of weight-bearing increased the measured volume of wear for 78% of patients at 1 year (Avg: 32.4 mm. 3. /yr) and 71% of patients at 2 years (Avg: 48.9 mm. 3. /yr). There were no significant (95% CI) correlations between patient demographics and wear rates. Discussion and Conclusion. This study demonstrated TKA wear to occur at a rate of approximately 10 mm. 3. /year and 39 mm. 3. /year in patients imaged supine versus standing, respectively, averaged over 2 years of clinical follow-up. In an effort to eliminate the effect of PE creep and deformation, wear was also calculated between 12 and 24 months as 9.3 mm. 3. (standing examinations), This value is comparable to wear rates obtained from retrieved TKRs. Weight-bearing exams produced better wear data with fewer negative wear rates and reduced variance. Limitations of this study include: supine patient imaging performed at post-op, no knee flexion performed, and unknown patient activity level. Strengths of this study include: large sample size of a single TKR system, linear regression of wear measurements and no requirement for implanted RSA beads with this method. Based on these results, in vivo volumetric wear of total knee replacement polyethylene can be reliably measured using model-based RSA and weight-bearing examinations in the short- to mid–term. For any figures or tables, please contact authors directly

Periprosthetic infection remains a clinical challenge that may lead to revision surgeries, increased spending, disability, and mortality. The cost for treating hip and knee total joint infections is anticipated to be $1.62 billion by 2020. There is a need for implant surface modifications that simultaneously resist bacterial biofilm formation and adhesion, while promoting periprosthetic bone formation and osseointegration. In vitro research has shown that nanotextured titanium promotes osteoblast differentiation, and upregulates metabolic markers of osteoblast activity and osteoblast proliferation. In vivo rat studies confirmed increased bone-implant contact area, enhanced de novo bone formation on and adjacent to the implant, and higher pull-out forces compared to non-textured titanium. The authors have advanced a benign electrochemical anodization process based on ammonium fluoride that creates a nanotube surface in as little as 10 minutes (Fig. 1), which can also integrate antibacterial nanosilver (Fig. 2). The work reported here summarizes in vitro post-inoculation and in vivo post-implantation studies, showing inherent inhibition of methicillin-resistant Staphylococcus aureus (MRSA) by titanium surfaces with nanotubes (TiNT), nanotubes with nanosilver (TiNT+Ag), plain (Ti), and thermal plasma sprayed (TPS) titanium. Ti6Al4V was the base material for all surfaces. In vitro studies evaluated Ti, TPS, four TiNT groups with varying nanotube diameters (60nm, 80nm, 110nm, 150nm), and TiNT+Ag. After seeding with MRSA (10. 5. , 10. 6. , and 10. 8. CFU/mL), the 110nm diameter nanotubes showed MRSA inhibition up to three-orders of magnitude lower than the Ti and TPS surfaces at 2, 6, and 48 hours. Following on the in vitro results, New Zealand White rabbits underwent a bilateral implantation of intramedullary tibial implants of the four material groups (4 mm outside diameter; 110nm NT diameter on TiNT and TiNT+Ag implants). One intramedullary canal was inoculated with clinically-derived MRSA (10. 5. CFU in broth) at the time of implantation; one canal had only culture media introduced (control). At a 2-week endpoint, limbs were harvested for analysis, including implant sonication with sonicant bacterial cultured, histology, and microcomputed chromatography. In the sonicant analysis cohort, TPS showed the lowest average MRSA count, while TiNT and TiNT+Ag were the highest. There was one sample each of TPS, TiNT and TiNT+Ag that showed no MRSA. After an additional 24-hour implant incubation, the TiNT and TiNT+Ag samples had no bacteria, but the TPS grew bacteria; therefore, the authors hypothesize that MRSA more readily releases from the TiNT and TiNT+Ag implants during sonication, indicating weaker biofilm adhesion and development. Histologic analysis is currently underway. In a therapeutic experiment, rabbits underwent bilateral implantation, followed by 1 week of infection development, and then 1 week of vancomycin treatment. At the endpoint, implants were sonicated and bacteria was quantified from the sonicant. TiNT showed viable MRSA at only 30% that of TPS-coated levels, while TiNT+Ag implants showed viable MRSA at only 5% that of TPS-coated levels (Fig. 3). These early results indicate that the TiNT and TiNT+Ag surfaces have some inherent antibacterial activity against MRSA, which may increase the efficacy of systemic antibiotic treatments in the setting of periprosthetic joint infections

Anterior cruciate ligament (ACL) reconstruction is the current standard of care for ACL tears. However, the results are not consistently successful, autografts or allografts have certain disadvantages, and synthetic grafts have had poor clinical results. The aim of this study was to determine the efficacy of tissue engineering decellularized tibialis tendons by recellularization and culture in a dynamic tissue bioreactor. To determine if recellularization of decellularized tendons combined with mechanical stimulation in a bioreactor could replicate the mechanical properties of the native ACL and be successfully used for ACL reconstruction in vivo. Porcine tibialis tendons were decellularized and then recellularized with human adult bone marrow-derived stem cells. Tendons were cultured in a tissue bioreactor that provided biaxial cyclic loading for up to 7 days. To reproduce mechanical stresses similar to hose experienced by the ACL within the knee joint, the tendons were subjected to simultaneous tension and torsion in the bioreactor. Expression of tendon-specific genes, and newly synthesized collagen and glycosaminoglycan (GAG) were used to quantify the efficacy of recellularization and dynamic bioreactor culture. The mechanical strength of recellularized constructs was measured after dynamic stimulation. Finally, the tissue-engineered tendons were used to reconstruct the ACL in mini-pigs and mechanical strength was assessed after three months. Dynamic bioreactor culture significantly increased the expression of tendon-specific genes, the quantity of newly synthesized collagen and GAG, and the tensile strength of recellularized tendons. After in vivo reconstruction, the tensile strength of the tissue-engineered tendons increased significantly up to 3 months after surgery and were within 80% of the native strength of the ACL. Our translational study indicates that the recellularization and dynamic mechanical stimuli can significantly enhance matrix synthesis and mechanical strength of decellularized porcine tibialis tendons. This approach to tissue engineering can be very useful for ACL reconstruction and may overcome some of the disadvantages of autografts and allografts

Background. Mobile-bearing (MB) total knee prostheses have been developed to achieve lower contact stress and higher conformity compared to fixed-bearing total knee prostheses. However, little is known about the in vivo kinematics of MB prostheses especially about the kinematics of polyethylene insert (PE). In vivo motion of PE during squatting still remains unclear. The objective of this study is to investigate the in vivo motion of MB total knee arthroplasty including PE during squatting. Patients and methods. We investigated the in vivo knee kinematics of 11 knees (10 patients) implanted with Vanguard Rotationg Platform High Flex (Biomet. (r). ). Under fluoroscopic surveillance, each patient did a wight-bearing deep knee bending motion. Motion between each component was analyzed using two- to three-dimensional registration technique, which uses computer-assisted design (CAD) models to reproduce the spatial position of the femoral, tibial components, and PE (implanted with five tantalum beads intra-operatively) from single-view fluoroscopic images. We evaluated the range of motion between the femoral and tibial components, axial rotation between the femoral component and PE, the femoral and tibial component, and the PE and tibial component, and AP translation of the nearest point between the femoral and tibial component and between the femoral component and PE. Results. The mean range of hyper-extension was 0.5±3.2° (range:-4.0 to 4.7°) and the mean range of flexion of 119.0±11.3°(range:98 to 137°). The external rotating femoral component relative to the tibial component demonstrated 8.6±3.2°(range:5.5 to 14.7°) for 0-120 degrees flexion. The PE rotated 9.6±4.5°(range:2.5 to 18.0°) externally relative to the tibial component, the femoral component rotated little relative to the PE. In upright standing position, the femoral component already rotated 1.2±9.8°(range:-16.5 to 15.9°) externally relative to the tibial component and the PE also rotated 0.8±9.8°(range:-16.1 to 16.0°) externally on the tibial tray. From 0°to 120°of flexion there was almost little A-P translation of the medial femoral condyle within 2 mm. The lateral condyle translated posteriorly with knee flexion. The average amount of posterior translation was 5.7±1.6 mm (range:2.5 to 7.5 mm). The femoral component relative to the tibial component exhibited a medial pivot pattern external rotation for 0-120 degrees flexion. Discussion and conclusion. In this study, we evaluated the in vivo motion of MB total knee arthroplasty including PE during squatting. About this total knee prosthesis, the mobile-bearing mechanism which advantages over fixed-bearing prosthesis to keep high comformity might work well, and arc of range of motion was maintained. Furthermore, in upright standing position, the femoral component and PE already rotated externally relative to the tibial component in almost equal measure. This indicated that, self-aligning mechanism, another characteristic of the MB prosthesis might also work well

Background. While posterior cruciate retaining (PCR) implants are a more common total knee arthroplasty (TKA) design, newer bi-cruciate retaining (BCR) TKAs are now being considered as an option for many patients, especially those that are younger. While PCR TKAs remove the ACL, the BCR TKA designs keep both cruciate ligaments intact, as it is believed that the resection of the ACL greatly affects the overall kinematic patterns of TKA designs. Various fluoroscopic studies have focused on determination of kinematics but haven't defined differentiators that affect motion patterns. This research study assesses the importance of the cruciate ligaments and femoral geometry for Bi-Cruciate Retaining (BCR) and Posterior Cruciate Retaining (PCR) TKAs having the same femoral component, compared to the normal knee. Methods. The in vivo 3D kinematics were determined for 40 subjects having a PCR TKA, 10 having a BCR TKA, and 10 having a normal knee, in a retrospective study. All TKA subjects had the same femoral component. All subjects performed a deep knee bend under fluoroscopic surveillance. The kinematics were determined during early flexion (ACL dominant), mid flexion (ACL/PCL transition) and deep flexion (PCL dominant). Results. During the first 30 degrees of flexion, the ACL played an important role, as subjects having a BCR TKA experienced kinematic patterns more similar to the normal knee. During mid flexion, both TKAs experienced random kinematic patterns, which could be due to the ACL and PCL being less active or resected in PCR TKA. In deeper flexion, both TKAs experienced kinematic patterns similar to the normal knee, thus supporting the assumption that the PCL played a dominant role [Fig. 1, Fig. 2]. All three groups generally experienced progressive axial rotation throughout flexion [Fig. 3]. On average, subjects having a PCR TKA experienced 112.3° of flexion, which was greater than the BCR subjects. Conclusions. Both the BCR TKA and normal groups experienced similar kinematic patterns, but the femoral geometrical differences from the anatomical condition may have influenced decreased motion compared to the normal knee. Both TKAs experienced similar kinematic patterns in deeper flexion, with the PCR TKA experiencing excellent weight-bearing flexion. Results from this study suggest that the cruciate ligaments can play a role in kinematics, but femoral geometry working with the ligaments may be an option to consider

Introduction. Reverse total shoulder arthroplasty (RTSA) is a semi-constrained joint replacement with an articulating cobalt-chromium glenosphere and ultra-high molecular weight polyethylene (PE). Because of its limited load bearing, surgeons and implant manufacturers have not elicited the use of highly cross-linked PE in the shoulder, and to date have not considered excessive PE wear in the reverse shoulder a primary concern. As the number of shoulder procedures is expected to grow exponentially in the next decade, however, it is important to evaluate how new designs and bearing materials interact and to have an understanding of what is normal in well-functioning joint replacements. Currently, no in vivo investigation into RTSA PE wear has been conducted, with limited retrieval and simulation studies. In vitro and in silico studies demonstrate a large range in expected wear rates, from 14.3 mm. 3. /million cycles (MC) to 126 mm. 3. /MC, with no obvious relationship between wear rate and polyethylene diameter. The purpose of this study is to evaluate, for the first time, both volumetric and linear wear rates in reverse shoulder patients, with a minimum six-year follow-up using stereo radiographic techniques. Methods. To date, seven patients with a self-reported well-functioning Aequalis Reversed II (Wright Medical Group, Edina, MN, USA) RTSA implant system have been imaged (mean years from surgery = 7.0, range = 6.2 to 9). Using stereo radiographs, patients were imaged at the extents of their range of motion in internal and external rotation, lateral abduction, forward flexion, and with their arm at the side. Multiple arm positions were used to account for the multiple wear vectors associated with activities of daily living and the shoulder's six degrees of motion. Using proprietary software, the position and orientation of the polyethylene and glenosphere components were identified and their transformation matrices recorded. These transformation matrices were then applied to the CAD models of each component, respectively, and the apparent intersection of the glenosphere into the PE recorded. Using previously validated in-house software, volumetric and maximum linear wear depth measurements were obtained. Linear regression was used to identify wear rates. Results. The volumetric and linear wear rates for the 36 mm PE liners (n = 5) were 39 mm. 3. /y (r. 2. = 0.86, range = 24 to 42 mm. 3. /y) and 0.09 mm/y (r. 2. = 0.96, range = 0.08 to 0.11 mm/y), respectively. Only two patients with 42 mm PE liners were evaluated. For these, volumetric and linear wear rates were 110 mm. 3. /y (r. 2. = 0.81, range = 83 to 145 mm. 3. /y) and 0.17 mm/y (r. 2. = 0.99, range = 1.12 to 1.15 mm/y), respectively. Conclusion. For the first time, PE wear was evaluated in the reverse shoulder in vivo. More patients are required for conclusive statements, but preliminary results suggest first order volumetric and linear wear rates within those predicted by simulation studies. It is interesting to note the increased wear with larger PE size, likely due to the increased contact area between congruent faces and the potential for increased sliding distance during arm motion

Introduction. Posterior cruciate ligament (PCL) preservation in total knee arthroplasty (TKA) is adovocated on the grounds that it provides better restoration of knee joint kinematics as opposed to PCL sacrifice. Mobile-bearing (MB) total knee prostheses have been in the market for a long time, but the PFC-Sigma Rotating Platform (RP) prosthesis (DePuy Orthopaedics, Inc, Warsaw, Ind) has been introduced in the market since 2000. Since, little is known about the in vivo kinematics of MB prostheses especially with cruciate retaining (CR). The objective of this study is to investigate the in vivo kinematics of MB RP-CR total knee arthroplasty during weight-bearing deep knee bending motion. Patients and methods. We investigated the in vivo knee kinematics of 20 knees (17 patients) implanted with PFC-Sigma RP-CR. All TKAs were judged clinically successful (Hospital for Special Surgery scores >90), with no ligamentous laxity or pain. Mean patient age at the time of operation was 78.0 ± 6.0 years. Mean period between operation and surveillance was 15.0 ± 9.0 months. Under fluoroscopic surveillance, each patient did a wight-bearing deep knee bending motion. Femorotibial motion was analyzed using 2D/3D registration technique, which uses computer-assisted design (CAD) models to reproduce the spatial position of the femoral, tibial components from single-view fluoroscopic images. We evaluated the range of motion, axial rotation, and antero-posterior (AP) translation of the nearest point between the femoral and tibial component. Results. Between the femoral and tibial components, the mean minimum flexion angle was on average 2.1±5.5 °. The mean maximum flexion angle was 118.0±9.9 °. The average range of motion was 115.8±12.8°. The femoral component relative to the tibial component demonstrated 5.5±3.7° external rotation for 0–120 degrees flexion. At full extension, the medial nearest point was −2.4±2.7 mm, and the lateral nearest point was −8.4±3.4 mm. The medial nearest point moved 1.3 mm anteriorly from full extension to 90° of knee flexion, and then moved 1.5mm posteriorly until maximum flexion. On the other hand, the lateral nearest point moved 0.4mm posteriorly from full extension to 90° of knee flexion, and then moved 3.6mm posteriorly until maximum flexion. At maximum flexion, the medial nearest point moved posteriorly to a final position of −2.6±3.3 mm and the lateral nearest point moved posteriorly to a final position of −12.5±3.6 mm [Fig.1]. From the results of bilateral contact positions at each flexion angle, patterns of kinematic pathways were determined. The kinematic pathway pattern was externally rotated due to a central pivot pattern from extension to 90° knee flexion. Subsequently from 90 to 120°, bilateral condyles moved backward. Discussion and conclusion. In this study, we have evaluated the in vivo kinematics of MB prostheses with cruciate retaining motion during deep knee bending motion under weight-bearing condition. The results in this study demonstrated that the kinematic pathway pattern was externally rotated due to a central pivot pattern from extension to 90° knee flexion. Subsequently from 90 to 120°, bilateral condyles moved backward. This indicated that PCL functions