Iwao Noda

Hydroxyapatite‐coating on titanium arc sprayed titanium implants

We developed a new titanium spray technique using an inert gas shielded arc spray (titanium arc spray). Hydroxyapatite (HA)-coating can be applied to the implant without any surface pore obstruction after the rough surface is made by this technique. Scanning electron microscopy (SEM) of various porous implant surfaces after HA-coating revealed that the bead and fiber metal-coated implants had either a pore obstruction or an uneven HA-coating. On the other hand, the titanium arc sprayed implant demonstrated an even HA-coating all the way to the bottom of the surface pore. In the first set of animal experiments (Exp. 1), the interfacial shear strength to bone of four kinds of cylindrical Ti-6A1-4V (Ti) implants were compared using a canine transcortical push-out model 4 and 12 weeks after implantation. The implant surfaces were roughened by titanium arc spray (group A-C) and sand blasting (group D) to four different degrees (roughness average, Ra = group A: 56.1, B: 44.9, C: 28.3, D: 3.7 microns). The interfacial shear strength increased in a surface roughness-dependent manner at both time periods. However, the roughest implants (group A) showed some failed regions in the sprayed layers after pushout test. In the second set of animal experiments (Exp. 2), four kinds of Ti implants; HA-coated smooth Ti (sHA) with Ra of 3.4 microns, bead-coated Ti (Beads), titanium arc sprayed Ti (Ti-spray) with Ra of 38.1 microns and HA-coated Ti-spray (HA + Ti-spray) with Ra of 28.3 microns were compared using the same model as that in Exp. 1. The interfacial shear strength of HA + Ti-spray was significantly greater than that of sHA and Beads at both time periods, and that of Ti-spray at 4 weeks. Although a histological examination revealed that HA-coating enhanced bone ingrowth, sHA showed the lowest shear strength at both time periods. SEM after pushout test showed that sHA consistently demonstrated some regional failure at the HA-implant substrate interface. HA + Ti-spray had many failed regions either at the HA-bone interface or within the bone tissue rather than at the HA-implant substrate interface. These results suggested that the HA-coated smooth surfaced implants had a mechanical weakness at the HA-substrate interface. Therefore, HA should be coated on the rough surfaced implants to avoid a detachment of the HA-coating layer from the substrate and thus obtain a mechanical anchoring strength to bone. HA-coating on this new type of surface morphology may thus lead to a solution to the problems of conventional HA-coated and porous-coated implants.

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.

The development of new titanium arc-sprayed artificial joints

Abstract The authors developed the new method of titanium porous coating onto Ti-6Al-4V and the coating layers and the substrates were evaluated in this study. The new method is inert gas-shielded arc spraying (ISAS), operated in an inert gas stream at atmospheric pressure, and the coatings showed far fewer voids and cracks in the layers and interfacial areas between the layer and the substrate compared with low-pressure plasma spray (LPPS) coatings commercially available currently. Wear of ISAS coatings by the blast erosion test was one sixth that of LPPS coatings, so the bonding strength between titanium porous particles is six times higher for ISAS coatings than for LPPS. The temperature of the heat treatment after ISAS coating process is 650 °C, which is below the beta transus and far lower than that of beads or wire mesh coatings, and the fatigue strength of the substrates is 38.2% relative to uncoated materials. Chemical analysis and X-ray diffraction analysis revealed that very few titanium reactants with oxygen and nitrogen were produced during the ISAS coating process. The new method of HA flame spray coating onto the surface of the ISAS coating (HA/ISAS) was also developed in this study. Animal experiments showed that the interfacial shear strength with surrounding bone was higher for the ISAS and HA/ISAS coatings than for the control smooth surface. From the histological findings, sound new bone formation was recognized around the HA/ISAS coatings at an early stage compared with ISAS coatings. The results indicate that ISAS and HA/ISAS coatings can be successfully used clinically for cementless joint replacements, and HA/ISAS coatings are expected to contribute more satisfactory clinical results in the long term.

Silver oxide-containing hydroxyapatite coating supports osteoblast function and enhances implant anchorage strength in rat femur.

Antibacterial silver with hydroxyapatite (Ag–HA) is a promising coating material for imparting antibacterial properties to implants. We previously reported that 3% (w/w) silver with HA (3% Ag–HA) has both antibacterial activity and osteoconductivity. In this study, we investigated the effects of Ag–HA on the in vitro osteoblast function and the in vivo anchorage strength and osteoconductivity of implants. Production of the osteoblast marker alkaline phosphatase, but not cytotoxicity, was observed in cells of the osteoblast cell line MC3T3‐E1 cultured on the 3% Ag–HA‐coated surface. These results were similar to those observed with silver‐free HA coating. In contrast, a significant high level of cytotoxicity was observed when the cells were cultured on a 50% Ag–HA‐coated surface. The anchorage strength of implants inserted into the femur of Sprague–Dawley (SD) rats was enhanced by coating the implants with 3% Ag–HA. On the 3% Ag–HA‐coated surface, both metaphyseal and diaphyseal areas were largely covered with new bone and had adequate osteoconductivity. These results suggest that 3% Ag–HA, like conventional HA, promotes osteogenesis by supporting osteoblast viability and function and thereby contributes to sufficient anchorage strength of implants. Application of 3% Ag–HA, which combines the osteoconductivity of HA and the antibacterial activity of silver, to prosthetic joints will help prevent postoperative infections.

Silver-Containing Hydroxyapatite Coating Reduces Biofilm Formation by Methicillin-Resistant Staphylococcus aureus In Vitro and In Vivo

Biofilm-producing bacteria are the principal causes of infections associated with orthopaedic implants. We previously reported that silver-containing hydroxyapatite (Ag-HA) coatings exhibit high antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In the present study, we evaluated the effects of Ag-HA coating of implant surfaces on biofilm formation. Titanium disks (14-mm diameter, 1-mm thickness), one surface of which was coated with HA or 0.5%–3.0% Ag-HA with a thermal spraying technique, were used. In vitro, the disks were inoculated with an MRSA suspension containing 4 × 105 CFU and incubated for 1-2 weeks. In vivo, MRSA-inoculated HA and 3% Ag-HA disks (8.8–10.0 × 108 CFU) were implanted subcutaneously on the back of rats for 1–7 days. All disks were subsequently stained with a biofilm dye and observed under a fluorescence microscope, and biofilm coverage rates (BCRs) were calculated. The BCRs on the Ag-HA coating were significantly lower than those on the HA coating at all time points in vitro (p < 0.05). Similar results were observed in vivo (p < 0.001) without argyria. Ag-HA coating reduced biofilm formation by MRSA in vitro and in vivo; therefore, Ag-HA coating might be effective for reducing implant-associated infections.

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.

Antibacterial properties of titanate nanofiber thin films formed on a titanium plate

A sodium titanate nanofiber thin film and a silver nanoparticle/silver titanate nanofiber thin film formed on the surface of a titanium plate exhibited strong antibacterial activities against methicillin-resistant Staphylococcus aureus, which is one of the major bacteria causing in-hospital infections. Exposure of the sodium titanate nanofiber thin film to ultraviolet rays generated a high antibacterial activity due to photocatalysis and the sodium titanate nanofiber thin film immediately after its synthesis possessed a high antibacterial activity even without exposure to ultraviolet rays. Elution of silver from the silver nanoparticle/silver titanate nanofiber thin film caused by the silver ion exchange reaction was considered to contribute substantially to the strong antibacterial activity. The titanate nanofiber thin films adhered firmly to titanium. Therefore, these titanate nanofiber thin film/titanium composites will be extremely useful as implant materials that have excellent antibacterial activities.

Comparison of Hydroxyapatite-Coated with Harris/Galante Porous Uncemented Total Hip Replacement – A Retrospective Matched Study and Experimental Study for the Improvement of HA-Coating

We compared the clinical results of Harris/Galante Porous (HGP) uncemented total hip replacement (THR) with that of hydroxyapatite (HA)-coated THR (HA-coating onto flat titanium) using a matched study (sex, age, weight, duration of follow-up, and diagnosis). Incidence of postoperative thigh pain was 31% in HGP and 6% in HA (p<0.005). Incidence of clear zone of zone 1 was 94% in HGP and 22% in HA (p<0.001), and that of zone 4 was 91% in HGP and 44% in HA (N.S.). HA-coating onto the porous titanium created by the Shielded Arc spray technique did not obstruct the pores of the surface and the sprayed layer was more tightly attached to the titanium substrate because of the lack of cracks or voids of the sprayed titanium layer commonly created by the plasma spray technique.