In vivo and in vitro bioactivity of a "precursor of apatite" treatment on polyetheretherketone.

We recently developed a surface treatment, "precursor of apatite" (PrA), for polyetheretherketone (PrA-PEEK) via a simple, low-temperature process aiming to achieve stronger and faster adhesion to bone. The treatment involves three steps: H2SO4 immersion, exposure to O2 plasma discharge, and alkaline simulated body fluid (alkaline SBF) treatment. This method produces homogeneous fine particles of amorphous calcium phosphate on the PEEK, and we confirmed that PrA-PEEK had excellent apatite formation ability in an SBF immersion test. In the present study using PEEK implants in rabbit tibia, mechanical tests, and histological and radiological analyses revealed that PrA provided the PEEK substrate with excellent bone-bonding properties and osteo-conductivity at early stages (4 and 8 weeks), extending to 16 weeks. In vitro study using MC3T3-E1 cells revealed via XTT assay that PrA on the PEEK substrate resulted in no cytotoxicity, though PrA treatment seemed to suppress gene expression of integrin ß-1 and Alp after 7-day incubation as shown by real-time PCR. On the whole, PrA treatment succeeded in giving in vivo bone-bonding properties to the PEEK substrate, and the treatment is a safe and promising method that can be applied in clinical settings. There was an inconsistency between in vivo and in vitro bioactivity, and this discrepancy indicated that apatite formation does not always need activation of osteoblasts at very early stage and that optimal conditions at cell and organism level may be different. STATEMENT OF SIGNIFICANCE: Polyetheretherketone (PEEK) is an attractive engineering polymer used for spine and dental surgery. To further improve clinical outcome of PEEK-based materials, we developed "Precursor of apatite" (PrA) treatment on the PEEK surface to confer bone-bonding properties. The advantages of this treatment are that it does not require high-temperature processing or special chemicals, and it is inexpensive. The present study clarified excellent in vivo bone-bonding property of PrA treatment. In addition, the results revealed important insights indicating that optimal conditions, especially wettability and crystallinity in calcium phosphate, differ at cell and organism levels. Moreover, our results indicated that prediction of in vivo bioactivity should be done in combination with multiple in vitro tests.

Fabrication of Bioactive Fiber-reinforced PEEK and MXD6 by Incorporation of Precursor of Apatite.

We aimed to develop an effective process to provide bioactivity to carbon fiber-reinforced polyetheretherketone (PEEK), glass fiber-reinforced PEEK and glass fiber-reinforced poly(m-xylyleneadipamide)-6 (MXD6), possessing similar elastic modulus to cortical bone in this study. First, we formed fine pores on the surface of each substrate by a short-time sulfuric acid treatment. Second, in order to provide hydrophilic property, we treated the surfaces of each substrate with oxygen plasma. Finally, we deposited fine particles of amorphous calcium phosphate (PrAp) in the pores by soaking each substrate in SBF adjusted at pH 8.40, 25.0°C, and subsequently kept at 70.0°C for 24 h. By this treatment, we obtained the bioactive fiber-reinforced polymers. By soaking thus-obtained each material in SBF, apatite formation was induced on the whole surface of each substrate within 1 day by PrAp deposited in the pores and high apatite-forming ability was performed on each material. The adhesive strength between the apatite layer showed high value by mechanical anchoring effect generated by the apatite formed in the pores. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2254-2265, 2018.

Effect of pores formation process and oxygen plasma treatment to hydroxyapatite formation on bioactive PEEK prepared by incorporation of precursor of apatite.

When bioinert substrates with fine-sized pores are immersed in a simulated body fluid (SBF) and the pH value or the temperature is increased, fine particles of calcium phosphate, which the authors denoted as 'precursor of apatite' (PrA), are formed in the pores. By this method, hydroxyapatite formation ability can be provided to various kinds of bioinert materials. In this study, the authors studied fabrication methods of bioactive PEEK by using the above-mentioned process. First, the fine-sized pores were formed on the surface of the PEEK substrate by H2SO4 treatment. Next, to provide hydrophilic property to the PEEK, the surfaces of the PEEK were treated with O2 plasma. Finally, PrA were formed in the pores by the above-mentioned process, which is denoted as 'Alkaline SBF' treatment, and the bioactive PEEK was obtained. By immersing in SBF with the physiological condition, hydroxyapatite formation was induced on the whole surface of the substrate within 1day. The formation of PrA directly contributed to hydroxyapatite formation ability. By applying the O2 plasma treatment, hydroxyapatite formation was uniformly performed on the whole surface of the substrate. The H2SO4 treatment contributed to a considerable enhancement of adhesive strength of the formed hydroxyapatite layer formed in SBF because of the increase of surface areas of the substrate. As a comparative study, the sandblasting method was applied as the pores formation process instead of the H2SO4 treatment. Although hydroxyapatite formation was provided also in this case, however, the adhesion of the formed hydroxyapatite layer to the substrate was not sufficient even if the O2 plasma treatment was conducted. This result indicates that the fine-sized pores should be formed on the whole surface of the substrate uniformly to achieve high adhesive strength of the hydroxyapatite layer. Therefore, it is considered that the H2SO4 treatment before the O2 plasma and the 'Alkaline SBF' treatment is an important factor to achieve high adhesive strength of hydroxyapatite layer to the PEEK substrate. This material is expected to be a candidate for next-generation implant materials with high bioactivity.