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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2871132","sourcedb":"PMC","sourceid":"2871132","source_url":"http://www.ncbi.nlm.nih.gov/pmc/2871132","text":"3.3. Chemical, Electrochemical, and Thermal Modifications\nThere are several experimental results on chemical, electrochemical, thermal, and combinations of these with regard to altering the Ti surface to facilitate better surface chemical, mechanical, and biological reactions. Endo [140] treated NiTi in 30% NHO3, then heated at 400 °C for 0.75 h, and NHO3 treatment, followed by boiling in water for 6–14 h. The variously treated NiTi surfaces were tested for dissolution resistance in bovine serum. It was found that (i) those stems thermally treated were found to have significantly lower metal ion release due to stable rutile oxide (TiO2) formation, (ii) human plasma fibronection (an adhesive protein) was covalently immobilized onto an alkylaminosilane derivate of NiTi substrate with glutaraldehyde, and (iii) the XPS spectra suggested that gamma-aminopropyltriethoxysilane (γ-APS) was bonded to the surface through metallosiloxane bonds (Ti-O-Si) formed via a condensation reaction between the silanol end of γ-APS and the surface of the hydroxyl group, with a highly cross-linked siloxane network formed after heat treatment of the silanized surface at 100 °C. Based on these findings, it was concluded that human plasma fibronectin was immobilized at the surface, and significantly promoted fibroblast spreading, suggesting that this chemical modification offers an effective means of controlling metal/cell interactions [140]. In study done by Browne et al. [141], hip replacement stems manufactured from the Ti-6Al-4V alloy were surface-treated and tested for dissolution resistance in bovine serum. Specimens were degreased in 1,2-dichloroethane vapor and surface treated in one of four ways: (1) 35% nitric acid for 10 min-typical commercial treatment, (2) 35% nitric acid for 16 h and rinsed in distilled water, (3) thermal heating in a furnace for 0.75 h at 400 °C, and (4) 35% nitric acid, then aged in boiling distilled water in a silica beaker for various times, 6, 8, 10, and 14 h. It was found that thermal treatment and aging of surface oxides promote the formation of dense rutile structure. This is effective in reducing metal ion dissolution (up to 80%), particularly in the early stages of implantation where the stem surface is equilibrating with its surroundings. This benefit is further enhanced on rough surfaces with an increased surface area. It was, therefore, concluded that (i) the thermal treatment and aging of the surface oxides are important with respect to cementless and porous implants, and (ii) such treatments could be incorporated in commercial manufacturing procedures to reduce the risk of metal dissolution being a contributory factor towards revision surgery [141].\nKrozer et al. [142] investigated the possible influence of an amino-alcohol solution on machined Ti surface properties. Screw-shaped CpTi implants and CpTi studs were used. They were rinsed (1) in running deionized water for 2 min, (2) NaCl solution for 2 min followed by deionized water washing, and (3) rinsed in 5% H2O2 for 2 min followed by deionizd water washing, and rinsed in deionized water for 2 min. The amino-alcohol solution was supplied to the sample surfaces, and four methods were used in order to remove the adsorbed alcohol molecules. It was shown that (i) rinsing in water, saline solution, and 5% H2O2 did not remove the amino-alcohol from the surface; however (ii) exposure to ozone produced by using a commercial mercury lamp in ambient air resulted in complete removal of the adsorbed amino-alcohol, and (iii) the presence of such a film most likely prevents re-integration to occur at the implant-tissue interface in vivo [141]. In study done by Rupp et al. [142], CpTi was first blasted with 354–500 μm large grits, followed by (1) HCl/HF/HNO3 etching, (2) HCl/H2SO4 etching, (3) HCl/H2SO4/HF/ oxalic acid + neutralized, and (4) HCl/H2SO4/HF/oxalic acid + oxidized. It was reported that the Ti modifications which shift very suddenly from a hydrophobic (high surface contact angle) to a hydrophilic (low surface contact angle) state adsorbed the highest amount of immunologically assayed fibronectin [143]. This is suggesting that microtexturing greatly influenced both the dynamic wettability of Ti implant surfaces during the initial host contact and the initial biological response of plasma protein adsorption.\nMacDonald et al. [144] investigated the microstructure, chemical composition, and wettability of thermally, and chemically modified Ti-6Al-4V disks, and correlated the results with the degree of adsorption between the radiolabeled fibronectin and Ti-6Al-4V alloy surface and subsequent adhesion of osteoblast-like cells. It was found that (i) heating either in pure oxygen or atmosphere resulted in an enrichment of Al and V within the surface oxide, (ii) heating (in pure oxygen or atmosphere) and hydrogen peroxide treatment, both followed by butanol treatment, resulted in a reduction in content of V, but not in Al, (iii) heating (oxygen/atm) or hydrogen peroxide treatment resulted in a thicker oxide layer and a more hydrophilic surface when compared with chemically-passivated controls (in 40% NHO3); however, the post-treatment with butanol resulted in a less hydrophilic surface than heating or hydrogen peroxide treatment alone, and (iv) the greatest increases in the adsorption of radiolabeled fibronectin following treatment were observed with hydrogen peroxide/butanol-treated samples followed by hydrogen peroxide/butanol and heat/butanol, although binding was only increased by 20–40% compared to untreated control. These experiments with radiolabeled fibronectin indicated that enhanced adsorption to the glycoprotein was more highly correlated with changes in chemical composition, reflected in V content and decrease in the V/Al ratio, than with changes in wettability. It was, therefore, concluded that an increase in the absolute content of Al and/or V, or in the Al/V ratio is correlated with an increase in the fibronectin-promoted adhesion of an osteoblast-like cell line [144]. Li et al. [145] modified the surface of CpTi (grade 2) implants by the micro-arc oxidation, operated under voltage ranging from 190, 230, 270, 350, 450 and 600 V to form a porous layer. It was found that (i) with increasing voltage, the roughness (from 0.3 to 2.5 μm) and thickness (from 1 μm to 15 μm) of the film increased, and (ii) the TiO2 phase changed from anatase to rutile. The micro-arc oxidation was carried out in an aqueous electrolyte with calcium acetate monohydrate and calcium glycerophosphate in deionized water. During the micro-arc oxidation, it was found that (i) Ca and P ions were incorporated into the oxide layer, (ii) the in vitro cell responses were also dependent on the oxidation condition, and (iii) with increasing voltage, the alkaline phosphatase activity increased, while the cell proliferation rate decreased. Preliminary in vivo tests of the micro-arc oxidation-treated specimens on rabbits showed a considerable improvement in their osseointegration capacity as compared to the un-modified CpTi implant [145].\nThe surface bioactivity of titanium was investigated after water and hydrogen plasma immersion ion implantation (PI3) by Xie et al. [146]. PI3 method excels in the surface treatment of components possessing a complicated shape such as medical implants. In addition, water and hydrogen plasma immersion ion implantation has been extensively studied as a method to fabricate silicon-on-insulator substrates in the semiconductor industry, and so it is relatively straightforward to transfer the technology to the biomedical field. Water and hydrogen were plasma-implanted into titanium sequentially. It was found that (i) after incubation in simulated body fluids for cytocompatibililty evaluation in vitro, bone-like hydroxyapatite was found to precipitate on the (H2O + H2) implanted samples, while no apatite was found on titanium samples plasma implanted with water or hydrogen alone, and (ii) human osteoblast cells were cultured on the (H2O+H2)-implanted titanium surface and they exhibited good adhesion and growth. It was, accordingly, suggested that plasma immersion ion implantation is a practical means to improve the surface bioactivity and cytocompatibility of medical implants made of titanium [146].\nRohanizadeh et al. [147] investigated methods of preparing different types of titanium oxide (TiO2) and their effects on apatite deposition and adhesion on titanium surfaces. CpTi discs were subjected to the following treatments: (1) heat treatment at 750 °C; (2) oxidation in H2O2 solution followed by heat treatment; (3) dipping in rutile/gelatin slurry; and (4) dipping in anatase/gelatin slurry. Surface-treated Ti discs were immersed in a supersaturated calcium phosphate solution to allow apatite deposition. It was shown that (i) the percentage of area covered by deposited apatite was highest in sample discs which were dipped in an anatase/gelatin slurry, compared to the other groups, (ii) apatite deposited on Ti discs pretreated in H2O2 solution demonstrated the highest adhesion to the titanium substrate, and (iii) the surface treatment method affects the type of TiO2 layer formed (anatase or rutile) and affects apatite deposition and adhesion on the Ti surface 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