Yutaka Yonekura

Development of novel thermal sprayed antibacterial coating and evaluation of release properties of silver ions

Several studies have addressed the use of antibacterial coating to reduce implant-associated infections. In this study, novel silver (Ag)-containing calcium-phosphate (CP) coating technology based on the thermal spraying method was developed. The coatings physical and chemical properties, in vitro antibacterial activity, hydroxyapatite (HA)-forming ability, and release of Ag ions were evaluated. An amorphous structure of the coating was confirmed by X-ray diffraction, and Ag residue in the coating was determined by elementary analysis. The coating showed strong antibacterial activity to methicillin-resistant Staphylococcus aureus in fetal bovine serum (FBS) along with HA-forming ability in simulated body fluid. Therefore, it is expected that the coating would confer antibacterial and bone bonding abilities to the implant surface. Time course release testing of Ag ions from the coating on immersion in FBS showed pronounced Ag release for up to 24 h after immersion, with consistent strong antibacterial activity at the early postoperative stage. In repeated testing, the amount of released Ag ions was about 6500 parts per billion (ppb, microg/L) for the first release test, after which it gradually decreased. However, retention of significant release of Ag ions after a sixth repeat implies that Ag release from the coating is slow in FBS.

In vivo antibacterial and silver-releasing properties of novel thermal sprayed silver-containing hydroxyapatite coating.

One of the serious postoperative complications associated with joint replacement is bacterial infection. In addressing this problem, we have previously described the development of a novel thermal spraying technology combining silver (Ag) showing antibacterial activity with hydroxyapatite (HA) displaying good biocompatibility and osteoconductivity, and reported the in vitro properties. This study evaluated serum Ag ion concentrations and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) using a subcutaneous rat model. HA loaded with 3 wt % of silver oxide (Ag-HA) and plain HA were sprayed on the surface of titanium disks. Ag-HA- or HA-coated samples were implanted into the back subcutaneous pockets of male Sprague-Dawley rats. Mean serum Ag ion concentration in the Ag-HA group increased to more than 50 ppb by 48 h after implantation, then decreased gradually to baseline levels. Mean (+/- standard error of the mean) number of viable MRSA on HA coating was (1.5 +/- 0.5) x 10(5), which is significantly more than the (1.1 +/- 0.4) x 10(4) on Ag-HA coating (p < 0.001). Ag-HA coating offers good abilities to release Ag ions and kill MRSA in vivo.

Silver oxide-containing hydroxyapatite coating has in vivo antibacterial activity in the rat tibia

Bacterial infection is a serious postoperative complication of joint replacement. To prevent infections related to implantation, we have developed a novel antibacterial coating with Ag‐containing hydroxyapatite (Ag‐HA). In the present study, we examined the antibacterial activity of Ag‐HA implant coatings in the medullary cavity of rat tibiae. Forty 10‐week‐old rats received implantation of Ag‐HA‐ or HA‐coated titanium rods, then were inoculated with ∼1.0 × 102 colony‐forming units of methicillin‐resistant Staphylococcus aureus. Bacterial counts were calculated for rats euthanized at 24, 48, and 72 h postoperatively. Serum levels of Ag (in the Ag‐HA group only) were calculated for rats euthanized at 24, 48, 72 h and 4 weeks. Radiographic evaluations of bone infection were also performed at 4 weeks. Tibiae from both groups showing infection were evaluated histologically. Significant differences in bacterial counts were seen at 24, 48, and 72 h. Mean concentrations of Ag in serum peaked about 48 h after implantation, then gradually decreased. Mean radiographic scores for infection were significantly lower with Ag‐HA implants than with HA implants. Histological examination showed better results for abscesses, bone resorption, and destruction of cortical bone around Ag‐HA‐coated implants. These results indicate that Ag‐HA coatings may help prevent surgical‐site infections associated with joint replacement.

Osteoconductivity of thermal-sprayed silver-containing hydroxyapatite coating in the rat tibia

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.

Acute and subacute toxicity in vivo of thermal-sprayed silver containing hydroxyapatite coating in rat tibia.

To reduce the incidence of implant-associated infection, we previously developed a novel coating technology using hydroxyapatite (HA) containing silver (Ag). This study examined in vivo acute and subacute toxicity associated with the Ag-HA coating in rat tibiae. Ten-week-old rats received implantation of HA-, 2% Ag-HA-, or 50% Ag-HA-coated titanium rods. Concentrations of silver in serum, brain, liver, kidneys, and spleen were measured in the acute phase (2–4 days after treatment) and subacute phase (4–12 weeks after treatment). Biochemical and histological examinations of those organs were also performed. Mean serum silver concentration peaked in the acute phase and then gradually decreased. Mean silver concentrations in all examined organs from the 2% Ag-HA coating groups showed no significant differences compared with the HA coating group. No significant differences in mean levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, creatinine, or blood urea nitrogen were seen between the three groups and controls. Histological examinations of all organs revealed no abnormal pathologic findings. No acute or subacute toxicity was seen in vivo for 2% Ag-HA coating or HA coating. Ag-HA coatings on implants may represent biologically safe antibacterial biomaterials and may be of value for reducing surgical-site infections related to implantation.

Transpositional Periacetabular Osteotomy with Allografting in Patients with Severe Dysplasia: Mid-Term Results

Aim The purpose of this study was to analyse the extent of surgical correction and the early clinical results obtained using periacetabular osteotomy with allogenic bone grafting in patients with severe acetabular dysplasia. Methods 44 hips in 38 patients were confirmed to have severe acetabular dysplasia and underwent this procedure. The mean follow-up period was 4.2 (range 1.5-8.2) years. Severe acetabular dysplasia was defined as a centre-edge angle less than 0°, an acetabular-head index less than 50% and an acetabular roof obliquity greater than 30°. Periacetabular osteotomy was performed with transpositional osteotomy of the acetabulum. The patients were divided into 2 groups according to the radiographic appearance: 34 hips in the early stage group and 10 hips in the advanced stage group. Postoperatively, the hips were radiographically assessed for dysplasia correction. The clinical results and hip function were measured using the Harris Hip Score. Results The average pre-operative Harris Hip Score improved from 70 to 91 points at the latest follow-up. The average centre-edge angle, acetabular-head index and acetabular roof obliquity improved from −9° to 36°, 41% to 91% and 31° to 2°, respectively. Continuity of the Shenton line improved from 15 to 35 hips. No instances of nonunion or of transported segment collapse were encountered in this series; however, a grafted allogenic bone was absorbed in 1 case. Conclusions The usage of allogenic bone grafting combined with periacetabular osteotomy is an effective technique for treating severe acetabular dysplasia. In this series, the early clinical and radiographic results were excellent.