Bacterial infection related to prosthetic replacement is one of the serious types of complications. Recently, there has been a greater interest in antibacterial biomaterials. In order to reduce the incidence of replacement-associated infections, we developed a novel coating technology of Hydroxyapatite (HA) containing silver (Ag). We reported the Ag-HA coating showed high antibacterial activity against E. coli, S. aureus and methicillin-resistant S. aureus (MRSA) under static condition. However, human bodies have a circulating body fluid, which is not a static condition. And the growth and the maturation of biofilm, which is said that a common course of persistent infections at a surgical site, are enhanced by the flow of broth in culture environment. Therefore, we evaluated whether the Ag-HA coating inhibits the biofilm formation on its surface or not by a biofilm-forming test under flow condition in this study.

Ag-HA or HA powder was sprayed onto the commercial pure titanium disks using a flame spraying system. The HA coating disks were used as negative control. The biofilm-forming methicillin sensitive S. aureus (BF-MSSA; Seattle 1945) strain and the BF-MRSA (UOEH6) strain were used. The pre-culture bacterial suspension (about 10⁵ colony forming units; CFU) was inoculated onto the Ag-HA and HA coating disks. After cultivation at 37 °C for 1 h, the disks were rinsed twice with 500 μL sterile PBS (-) to eliminate the non-adherent bacteria. The number of the adherent bacteria on these disks was counted using culture method. After rinsing, the disks were transferred into petri-dish containing Trypto–Soy Broth (TSB) + 0.25% glucose with a stirring bar on the magnetic stirrer and they were cultured at 37°C for 7 days. In the meantime, the stirring bar was spun at 60 rounds per minute. Then, the disks were immersed in a fluorescent reagent to stain the biofilm. Finally, the biofilm on each disk was observed by a fluorescence microscope and the biofilm-covered rate on the surfaces of them was calculated using the NIH image software.

The number of the bacteria on these disks was not so different between Ag-HA and HA coating after rinsing. After biofilm-forming test, the coverage of the biofilm of BF-MSSA was 2.1% and 81.0% on the Ag-HA and HA coatings, respectively. Similarly, in the case of BF-MRSA, it was 7.7% and 72.0% on the Ag-HA and HA coatings, respectively. Though bacteria slightly adhered, biofilm was hardly observed on the Ag-HA coating. The biofilm on the HA coating was extensive and mature. The inhibition effect of biofilm formation on the Ag-HA coating might be ascribed to the antibacterial effect by Ag ions released from the coating. Because Ag ions have a broad spectrum of antibacterial activity against pathogens, including biofilm forming bacteria, they inhibited the biofilm formation on the Ag-HA coating by killing adherent bacteria. Even in a flow condition, it was suggested that the AgHA shows the antibacterial activity, though the conditions in this work are different from those in living body.

The objective of this study is to introduce the forces acting on the knee joint while ascending from kneeling. Our research group has developed a new type of knee prosthesis which is capable of attaining complete deep knee flexion such as a Japanese style sitting, seiza. Yet we could not set up various kinds of simulation or experiment to assess the performance of our prosthesis because the data about joints' forces during the ascent from deep knee flexion are lacking. Considering this circumstance, we created a 2D mathematical model of lower limb and determined knee joint force during ascent from kneeling to apply them for the assessment of our prosthesis.

Ten male and five female healthy subjects participated in the measurement experiment. Although the measurement of subjects' physical parameters was non-invasive and direct, some parameters had to be determined by referring to the literature. The data of ground reaction force and each joint's angle during the motion were collected using a force plate and video recording system respectively. Then the muscle forces and the joints' forces were calculated through our mathematical model. In order to verify the validity of our model approach, we first introduced the data during the activities with small/middle knee flexion such as level walking and rising from a chair; these kinds of data are available in the literature. Then we found our results were in good agreement with the literature data. Next, we introduced the data during the activities with deep knee flexion; double leg ascent [Fig.1 (a)] and single leg ascent [Fig.1 (b)] from kneeling without using the upper limbs.

The statistics of the maximum values on the single knee joint for all the subjects were; during double leg ascent, F_max = 4.6±0.6 (4.3-5.2) [BW: (force on the knee joint)/(body weight)] at knee flexion angle of b =140±8 (134-147)°, during double leg ascent, F_max = 4.9±0.5 (4.0-5.6) [BW] at b = 62±33 (28-110)° for the dominant leg, and F_max = 3.0±0.5 (22.2-3.8) [BW] at b = 138±6 (130-150)° for the supporting leg respectively. We found that the moment arm length, i.e., the location of muscle insertion significantly affected the results, while ascending speeds did not affect the results much. We may conclude that the single leg ascent should be recommended since F_maxdid not become large while deep knee flexion. The values could be used for assessing the strength of our knee prosthesis from the risk analysis view point.

A silver-containing hydroxyapatite (Ag-HA) coating has been developed using thermal spraying technology. We evaluated the osteoconductivity of this coating on titanium (Ti) implants in rat tibiae in relation to bacterial infection in joint replacement.

At 12 weeks, the mean affinity indices of bone formation of a Ti, an HA, a 3%Ag-HA and a 50%Ag-HA coating were 97.3%, 84.9%, 81.0% and 40.5%, respectively. The mean affinity indices of bone contact of these four coatings were 18.8%, 83.7%, 77.2% and 40.5%, respectively. The indices of bone formation and bone contact around the implant of the 3%Ag-HA coating were similar to those of the HA coating, and no significant differences were found between them (bone formation, p = 0.99; bone contact, p = 0.957). However, inhibition of bone formation was observed with the 50%Ag-HA coating.

These results indicate that the 3%Ag-HA coating has low toxicity and good osteoconductivity, and that the effect of silver toxicity on osteoconductivity depends on the dose.

We have developed a new type of knee prosthesis which is capable to make 180° knee flexion, and have designated it as Complete flexion knee (CFK). Since the kinematics and kinetics of knee prosthesis vary depending not only on its articulating surface shapes but also on the stiffness of soft tissues, its performance should be assessed under various kinds of lower limb activities.

The objective of this study is to perform simulation analysis of various lower limb activities to evaluate the performance of CFK using the 2D and the 3D mathematical models. Kinematic analyses using X-ray picture or stress analyses using FEM are extensive however, kinematic analyses can not introduce stresses and FEM can not introduce kinematics. Mathematical model analyses can introduce vital information about kinematics and kinetics at the same time.

First, we carried out an in-vitro experiment using cadaver knee under the condition of passive knee flexion-extension. After that, we performed a simulation using the same parameter variables as the in-vitro experiment in order to assess the validity of our 2D and 3D models by comparing the results about the joint contact forces and kinematics with those from the experiment.

In the in-vitro experiment, the femoral bone of a cadaver knee was fixed on a jig. In order to secure the tibiofemoral contact, each muscle was pulled with constant force respectively. Then the tibia was carried through from 40° to 140° of knee flexion. The contact forces between the femur and the tibia were measured by a load sensor. During the process, fluoroscopic images were taken, and then 3D positions/orientations of the tibia relative to the femur were introduced from the images using the pattern matching method.

Our 2D and 3D models of total knee arthroplastic joint included the tibio-femoral and patello-femoral compartments, incorporating major muscles, patella tendon and primary ligaments. The patella tendon and primary ligaments were represented with non-linear springs, whose mechanical properties were determined from the literature. In our 2D model, “thigh and calf” contact was taken into account at deep knee flexion.

Using our 3D model, the simulation was performed up to 100° of knee flexion. After that we had to alternate the model from the 3D to the 2D because the patella stacked into the femoral intercondylar, the thigh-calf contact occurred and the 3D model did not introduce the converged solution.

Over all, both the experimental and simulation results were in good agreement with each other. The results from the simulation showed that the contact points were located unusually anteriorly. The post-cam contact occurred at 44° of knee flexion, indicating that the tibia was strongly pulled to the posterior. As for the contact resultant force, large differences between simulation and experiment were found. This may be because the soft tissues of the cadaver were not intact, while we determined their properties from the literature in the simulation.

Surgical site infection related to orthopaedic implants is one of the serious complications. In the previous works, we developed a novel thermal spraying technology combined silver with hydroxyapatite (HA) in order to resolve such problems, and reported the property and antibacterial effect of them in vitro. However, no previous reports have investigated in vivo. Therefore, we monitored serum silver level in rats to clarify in vivo kinetics of silver released from the coating.

HA loaded with 3 wt % of silver oxide (HA-Ag) and plain HA powder were sprayed on surface of titanium disks (20 mm diameter × 1 mm thick) by the flame spraying, which is a kind of thermal spraying method with acetylene torch. All these test pieces were obtained from Japan Medical Materials Corporation (JMM, Osaka, Japan). Both samples were implanted singly into the back subcutaneous pockets of male Sprague-Dawley rats (150–200 g). Rats were housed individually and given ad libitum access to food and water. After 24 h, 48 h, 7 d, 14 d and 28 d, the rats were sacrificed, and then the blood was drawn from common iliac vein. All procedures were operated under anesthesia. These blood samples were spun down and serum silver levels were measured by an inductively coupled plasma mass spectrometry.

The average serum silver level in HA-Ag group had increased to more than 40 ppb until 48 h after implantation, and then decreased rapidly to normal level. There were significant differences (p < 0.05) between HA-Ag and HA group, at each measurement period.

This is the first report to elucidate the serum silver level in rats implanted HA-Ag coatings. To date, reported coating technologies have included direct-loading antibacterial agents or heavy metals including silver with prosthesis base. The combine technology HA with silver would be effective in not only antibacterial but also osteoconductive respect. Our experimental results highlight the following 2 features: the serum silver levels peaked relatively early, and the levels reduced immediately to normal level after the peak. Therefore, we speculate that the released silver would not be accumulated generally, which not contribute long-term toxicity, and the coating would be suitable for prevention of early surgical site infections.

This study provides novel and important information on in vivo release- property for HA-Ag coating, and suggests this coating is effective against not late but rather early infection related to orthopaedic implants.

Binary Surface type knee prosthesis (bisurface knee) has successfully been utilized in total knee arthroplasty (TKA) in order to improve flexional motion, especially, deep flexion. Binary surface means that the knee prosthesis has two different bearing structures, that is, normal condylar surfaces and ball-socket structure. The ball and the socket are placed between the condylar surfaces of the femoral component and the tibial insert, respectively. Two different designs of bisurface knee have been proposed so far and only one model called KU has been utilized in clinical applications. The other model called CFK is still under development and characterized to have a post-cam structure to stabilize the knee motion. These bisurface knees are expected to attain deep flexional motion and therefore, it is important to understand their safety and durability at high flexion angles. In the present study, the finite element analysis (FEA) is conducted to characterize the mechanics of the bisurface knees under deep knee flexion. Risk assessment of the bisurface knees are then performed based on the FEA results.

Detailed 3D-FEA models are constructed using CAD data and deep knee flexion corresponding to a squatting motion is reproduced by using spring models and proper boundary conditions. The spring models attached to the tibial component are used to express the mechanical effects of soft tissues. Internal rotational motion is also considered with the flexional motion. The femoral and the tibial components are assumed to be rigid and the tibial insert made of UHMWPE is an elastic-plastic solid having a nonlinear constitutive relation determined from experiments. The femoral component is rotated continuously from 0° to 135° to express the flexional motion and the tibial component is also rotated to express internal rotation.

The equivalent stress of the condylar surface of the new CFK model is almost equivalent to that of the KU model during flexion from 0° to 90°, however, the stress values are different at the angles higher than 90°. At higher angles of flexion than 90°, the bearing surface of the KU consists of the condylar and the socket surfaces, while the bearing surface of the CFK consists of the socket surface only. Therefore, the CFK exhibits higher stress than the KU at these high angles. The ball-socket bearing system enables these bisurface knees to be adapted to deep flexional motion. The CFK is trying to achieve higher flexion angles than the KU by employing the modified ball-socket bearing structure, however, higher stress concentration on the socket surface of the CFK may hasten degradation of the tibial insert. It is also found that the stress concentration on the socket surfaces increase with increase of the internal rotation angle and therefore, the risk of damage of the tibial insert becomes higher with internal rotation.

In summary, 3D dynamic FEA is utilized to make a risk assessment of the bisurface knees and the computational results suggest that the design of the ball-socket structure is one of the most important factors to determine the safety and durability of the knees.

Bacterial infections related to orthopaedic implants is one of the serious types of complications. Recently, there has been a greater interest in antibacterial biomaterials. However, antibacterial evaluations of each material are inconsistant, so intercomparison of the antibacterial performance is difficult. This study focused on the Japanese Industrial Standards test (JIS Z2801), which is used for antibacterial evaluation of commodities. The study investigated a suitable evaluation method for in vitro antibacterial activity of biamaterials. In 2007, JIS Z2801 test was approved as international standard ISO 22196.

Hydroxyapatite (HA) powder containing 3 wt % of silver oxide (Ag) was sprayed on the surface of titanium disks with the thermal spraying method, using an acetylene torch. This coating has been proved to generate strong antibacterial activity in previous studies. The antibacterial activity was examined with the JIS Z 2801 test and modified JIS Z2801 test. The bacterial strains used in JIS Z2801 test were Escherichia coli (E.coli), Staphylococcus aureus (S.aureus). Bacterial culture medium was instilled onto the surface of the test disks (about 106 cells/ml) and covered with polystyrene films. After cultivation in 1/500 Nutrient Broth for 24 h at 35°C, the bacteria was washed out with the broth. The numbers of viable bacteria in the broth were counted with the agar plate culture method. Additionally, Modified JIS Z2801 test was performed. Modified points were added to the bacterial strain of biofilm-forming methicillin-resistant S.aureus (BF-MRSA), using Fetal Bovine Serum (FBS) as a culture medium, and cultivated at 37°C.

In the JIS Z2801 test, Antibacterial activity values of the HA-Ag disk were composed against E.coli 4.1 and S.aureus 5.0. In the modified JIS Z2801 test, antibacterial activity values against E.coli, S.aureus and BF-MRSA were 8.2, 5.5, and 7.1. When this value is greater than 2.0, it shows there is antibacterial activity. The titanium disk coated with HA-Ag showed antibacterial activity in both tests.

The JIS Z2801 test is designed to evaluate comodities in poor nutritional environment. However, the environment in the body is eutrophic. It is easy to make bacterial growth. For this reason, it is necessary to consider evaluating for biomaterials with suitable method considered in vivo. In this study, to examine the condition like that found in the body, we cultivated FBS at 37°C. In addition, the antibacterial activity against BF-MRSA was examined to consider the bacterial infection related to orthopaedic implants. The modified JIS Z2801 test showed that it is a suitable evaluation method for in vitro antibacterial activity of biomaterials.

Bacterial infection related to orthopaedic implants is a significant complication today. One of the ways to reduce the incidence of implant-associated infections is assumed to give antibacterial activity to surface of implant itself. We focused attention on Ag, because it has a broad antibacterial spectrum, strong antimicrobial activity and low toxicity. In the previous works, sputtering, electrochemically deposition and sol-gel coating of Ag-containing hydroxyapatite (HA) have been reported. However, since practical technique of HA coating widely used for medical and dental implants has been the “thermal spraying” technique over the last two decades, we aimed at developing the novel thermal spraying technology for Ag-HA coating with antibacterial activity. In this study, physical and chemical properties, in vitro antibacterial activity, inhibition activity of bacterial attachment, HA-forming ability, cytotoxicity and release of Ag ions of the thermal-sprayed Ag-HA coating were evaluated.

HA powder containing 3wt % of silver oxide (Ag2O) was sprayed on surface of titanium disks by the thermal spraying method using acetylene torch. SEM images showed a typical structure of the thermal-sprayed coating and the X-ray diffraction (XRD) pattern of the coating showed an amorphous structure. Ag residue in the coating was determined by the elementary analysis. The coating showed strong antibacterial activity and inhabitation activity of bacterial attachment to the methicillin-resistant Staphylococcus aureus (MRSA) in fetal bovine serum (FBS). On the other hand, the coating showed fast HA-forming ability in simulated body fluid (SBF) and no cytotoxicity related to Ag contained in the coating. Therefore, it is expected that the thermal-sprayed Ag-HA coating provides antibacterial and bone-bonding ability on the surface of the implant itself. In addition, though the HA coating is generally liable to adhere bacteria, the thermal-sprayed Ag-HA coating overcomes this problem.

Pre-evaluation of release of Ag ions from the Ag-containing ceramic powders indicated that the releasing behavior of Ag ions in SBFs is dependent on the existing form of Ag in the Ag-containing material. It is assumed that most of Ag components in the Ag-HA coating are not retained as metallic Ag but as Ag2O in the amorphous layer. Time-course release tests of Ag ions from the coating in FBS showed a large release rate of Ag ions until 24 h after the immersion. It is expected that the Ag-HA coating could show strong antibacterial activity at the early post-operative stage. In the repeated release testing, the amount of released Ag ions was about 6500 ppb for the first release test, after which it gradually decreased. However, a significant release amount of Ag ions was observed even after the sixth repeat test. Therefore, it was assumed that the thermal-sprayed Ag-HA coating has a slow-release property of Ag ions in FBS.

One third of the world population have a life style to sit sedentary on a floor. Thus far the patients who had undergone TKA surgery loose deep flexion of the knee and various designs of artificial knee joint capable of deep knee flexion have been proposed. Among them, Bi-surface knee prosthesis (Kyocera Inc., Japan) is of special interest because of its unique design with a ball-and-socket joint. Although some patients attained a sedentary sitting with this prosthesis, the X-ray studies revealed that the femoral condyles and tibial insert tended to separate at about 150° of knee flexion, indicating a risk of subluxation when standing up.

Thus we have developed CFK (Complete Flexion Knee, Japan Medical Material Co., Japan) by further improving Bi-surface knee to enable the patient to make knee flexion as much as 180°. Our CFK has a ball-and-socket joint and whose socket part is jutted to form a tibial post. Since the ball and the cam become into a single sphere and the ball-socket and post-cam joints form a spherical bearing, CFK can provide high stability and mobility at the same time.

Besides its kinematic performance, CFK has to be assessed with its strength and durability. Since the durability of an artificial knee joint is attributed to wear of the polyethylene insert, it is essential to focus on determining the stress on it. Although the FEM analyses have been most extensive for stress analysis, whose results greatly depend upon the way how to create the meshes. The stress values introduced from the FEM are the Von Misses stresses; while wear is mainly attributed to the shear stresses. For these reasons, we employed a photoelasticity for determining the magnitude and distributions of stresses on the insert.

The models of Bi-surface, CFK and a conventional posterior stabilizer knee, Scorpio NRG (Stryker Co., USA) were used for the experiments. Epoxy resins (Araldite AER 250, 2400, Ciba Geigy Co., Japan) were selected to fabricate the tibial insert models. Special equipment was used to apply 2 kg force on the model by setting knee flexion angle at 0°, 30°, 60°, 90° and 120° respectively. After that the stressed model was sliced along the anterio-posterior direction and photoelastic fringes in each slice were observed. The results demonstrated that while knee angle was smaller than 90°, shear stress on the lateral slice became higher in the order, NRG, CFK, and Bi-surface, indicating NRG has high conformity in the condylar surface. After knee angle bacame larger than 90°, shear stress on the mid-posterior slice became higher in the order, CFK, Bi-surface and NRG. We may conclude that CFK has optimal configuration at deep knee flexion not only for kinematic but also for load bearing viewpoints.

In the case of a complete dislocated hip or a severe deformity of the proximal femur, total hip arthroplasty (THA) can still be combined with a proximal femoral osteotomy for shortening femur or correcting the deformity if needed. Subtrochanteric femoral shortening and a corrective osteotomy are considered to be an integral part of THA for such cases. A precise osteotomy is mandatory to achieve good results. Although, the freehand excision of V-shaped subtrochanteric osteotomy used to be performed frequently, this procedure was also subject to some pitfalls, such as poor coaptation of the osteotomy surface. A new device was thus developed to perform a V-shaped osteotomy in an identical central axis between the distal and proximal femur. The purpose of this study was to evaluate the efficacy of the device by comparing the perioperative results with those of a free-hand subtrochanteric osteotomy.

From 1999 to 2002, THA combined with a double-chevron subtrochanteric osteotomy was performed by free hand (free hand group). From 2003 to 2007, THA combined with a double-chevron subtrochanteric osteotomy was performed using a new device (device group). The free hand group included 27 hips in 21 patients. The mean age of the patients (23 females and 3 males) at the time of the operation was 58 years. Fourteen were completely dislocated hips and 13 followed various proximal femoral osteotomies. The device group included 102 hips in 79 patients. The mean age of thepatients (70 females and 9 males) at the time of the operation was 62 years. Seventy two were completely dislocated hips and 26 followed various proximal femoral osteotomies. Four parameters were used to evaluate the efficacy of the device:

operation time,

The mean operation time, total blood loss, and C-reactive protein in the device group all significantly decreased in comparison to the free hand group. The decreases ranged from; 132 to 96 minutes (p< 0.01), 1346 to 999 g (p< 0.01), 4.9 to 3.0 mg/dl (p< 0.05), respectively. Two types of complications were observed at the osteotomy site. Pseudoarthrosis at the osteotomy site was observed one case in each group and both of these cases underwent a stem revision (4% in the freehand group and 1% in the device group). A femoral shaft split was observed in 3 cases in the freehand group (11%) and 3 cases in the device group (3%) and all 6 cases were treated conservatively. There were no instances of nerve palsy, infections, or thromboembolic events resulting from these procedures.

The above described new device allowed for the easy and accurate performance of a subtrochanteric V-shaped osteotomy with THA for either a completely dislocated hip or a severely deformed proximal femur.

Using thermal spraying technique, we developed a novel titanium material coated with hydroxyapatite (HA) containing silver (Ag). In this study, antibacterial activities of the material were examined both in vitro and in vivo.

Two different titanium test pieces were prepared. One is the test piece that was coated by HA containing Ag (HA-Ag) and the other is that was coated by HA only, used as a negative control. Antibacterial activity and efficacy of HA-Ag against Staphylococcus aureus, Escherichia coli, and biofilm-forming methicillin-resistant S. aureus (BF-MRSA) was examined by using the Japanese Industrial Standards test (JIS Z2801). Furthermore, surface area where BF-MRSA was attached and proliferated on the test pieces after 24 hours of incubation was calculated by means of scanning electron microscope (SEM). To investigate the antibacterial activity in vivo, the test pieces were inserted subcutisly into the back of SD rats, and BF-MRSA was inoculated into the inserted pieces. On the 7th day after the inoculation, the numbers of adherent bacteria to the pieces were countered by a sterile cotton-tipped swabs method.

By the JIS Z2801 test, HA-Ag showed 104 to 105 times stronger antibacterial activity than HA against all bacteria tested in this study. SEM studies revealed the HA-Ag coated material had 30 to 50 times smaller area of attached bacteria than control. In vivo study showed that viable bacterial numbers on surfaces of HA-Ag were 1000 times less than control. These results indicated that the HA-Ag coated materials have antibacterial activities both in vitro and in vivo.

Titanium coated with HA containing Ag has a possibility to be a novel antibacterial biomaterial.

Six major and seven minor diagnostic criteria have been developed by the Japanese Investigation Committee for osteonecrosis of the femoral head (ONFH). We have carried out a multicentre study to clarify these.

We studied prospectively 277 hips in 222 patients, from six hospitals, who had ONFH and other hip pathology and from whom histological material was available. We identified five criteria with high specificity: 1) collapse of the femoral head without narrowing of the joint space or acetabular abnormality on radiographs, including the crescent sign; 2) demarcating sclerosis in the femoral head without narrowing or acetabular abnormality; 3) a ‘cold-in-hot’ appearance on the bone scan; 4) a low-intensity band on T1-weighted images (band pattern); and 5) evidence of trabecular and marrow necrosis on histological examination. With any combination of two of these criteria, the sensitivity and specificity of the diagnosis were 91% and 99%, respectively.