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{"project":"2_test","denotations":[{"id":"20480036-8406955-52068622","span":{"begin":4500,"end":4502},"obj":"8406955"},{"id":"20480036-4589049-52068623","span":{"begin":5022,"end":5024},"obj":"4589049"},{"id":"20480036-6715394-52068624","span":{"begin":5025,"end":5027},"obj":"6715394"},{"id":"20480036-3521751-52068625","span":{"begin":5573,"end":5575},"obj":"3521751"},{"id":"20480036-11432653-52068626","span":{"begin":7546,"end":7548},"obj":"11432653"},{"id":"20480036-11432653-52068627","span":{"begin":7866,"end":7868},"obj":"11432653"},{"id":"20480036-1633230-52068628","span":{"begin":10123,"end":10125},"obj":"1633230"},{"id":"20480036-1613024-52068629","span":{"begin":10535,"end":10537},"obj":"1613024"},{"id":"T61848","span":{"begin":4500,"end":4502},"obj":"8406955"},{"id":"T72396","span":{"begin":5022,"end":5024},"obj":"4589049"},{"id":"T77168","span":{"begin":5025,"end":5027},"obj":"6715394"},{"id":"T52241","span":{"begin":5573,"end":5575},"obj":"3521751"},{"id":"T80911","span":{"begin":7546,"end":7548},"obj":"11432653"},{"id":"T78738","span":{"begin":7866,"end":7868},"obj":"11432653"},{"id":"T79362","span":{"begin":10123,"end":10125},"obj":"1633230"},{"id":"T62153","span":{"begin":10535,"end":10537},"obj":"1613024"}],"text":"2.2.1. Biological Compatibility (Biocompatibility)\nThe service conditions in the mouth are hostile, both corrosively and mechanically. All intraorally placed parts are continuously bathed in saliva, an aerated aqueous solution of about 0.1 N chlorides, with varying amounts of Na, K, Ca, PO4, CO2, sulphur compounds and mucin [18]. The pH value is normally in the range of 5.5 to 7.5, but under plaque deposits it can be as low as 2. Temperatures can vary ±36.5 °C, and a variety of food and drink concentrations apply for short periods. Loads may be up to 1,000 N (with normal masticatory force ranging from 150 N to 250 N) [18], sometimes at an impact-load superimposed. Trapped food debris may decompose to create sulphur compounds, causing placed devices discoloration [18]. With such hostile conditions, biocompatibility of metallic materials essentially equates to corrosion resistance because it is thought that alloying elements can only enter the surrounding organic system and develop toxic effects by conversion to ions through chemical or electrochemical process.\nAs mentioned before, the interface zone between placed implant and receiving hard/soft tissue is strongly governing the success and longevity of placed implant. Hence, there are two major research approaches; one is looking at the interface from foreign implant material side, the other is from vital tissue side. Although this review’s principle scope is aiming at the material’s side, it would be worth to take a brief look at what is happening right after the placing the implant surgically at vital traumatized hard tissue.\nAfter implant placement, initial healing of the bony compartment is characterized by formation of blood clots at the traumatized wound site, protein adsorption and adherence of polymorphonuclear leukocyte [19]. Then approximately two days after placement of the implant, fibroblasts proliferate into the blood clot, organization begins, and an extra-cellular matrix is produced. Approximately one week after the implant is placed, appearance of osteblast-like cells and new bone is seen. New bone reaches the implant surface by osseoconduction (through growth of bone over the surface and migration of bone cells over the implant surfaces) [19].\nWhy do titanium and its alloys show such good biocompatibility compared with other alloys? The answer to this question is generally that titanium is passive in aqueous solutions, and the passive film that forms on titanium is stable, even in a biological system including chemical and mechanical environments. Such an interpretation is true in many cases. However, the presence of the passive film is only part of the answer when we consider the complex interfacial phenomena to be found between titanium and a biological system, in both biological and biomechanical environments [20,21]. There are certain criteria for any potential metallic materials to be evaluate excellent corrosion resistant, including (1) ease to be oxidized, (2) strong adherence of formed oxide to the substrate, (3) dense of formed oxide, and (4) protectiveness of formed oxide. The Pilling –Bedworth (P-B) ratio is the very simple indication to judge whether the formed oxide is protective or not [22]. If P-B ration is less than 1, since oxide occupies small volume than the metal, so that formed oxide is porous and non-protective. If it is larger than 2, since oxide occupies a large volume and may flake from the surface, exposing fresh substrate surface and again exhibits non-protectiveness. If P-B ration is between 1 and 2, the volume of oxide is similar to that of metal, so that the formed oxide is adherent to substrate, nonporous, and protective. It was calculated that P-B ratio for TiO2 formation is 1.76, indicating that the formed TiO2 is protective. Titanium is a highly reactive metal and will react within microseconds to form an oxide layer when exposed to the atmosphere [23]. Although the standard electrode potential was reported in a range from −1.2 to −2.0 volts for the Ti ↔ Ti3+ electrode reaction [24], due to strong chemical affinity to oxygen, it easily produces a compact oxide film, ensuring high corrosion resistance of the metal. This oxide, which is primarily TiO2, forms readily because it has one of the highest heats of reaction known (ΔH = −915 kJ/mole) (for 298.16°–2,000°K) [25]. It is also quite impenetrable to oxygen (since the atomic diameter of Ti is 0.29 nm, the primary protecting layer is only about 5 to 20 atoms thick) [26]. The formed oxide layer adheres strongly to the titanium substrate surface. The average single-bond strength of the TiO2 to Ti substrate was reported to be about 300 kcal/mol, while it is 180 kcal/mol for Cr2O3/Cr, 320 kcal/mol for Al2O3/Al, and 420 kcal/mol for both Ta2O5/Ta and Nb2O5/Nb [27].\nDuring implantation, titanium releases corrosion products (which is mainly titanium oxide or titanium hydro-oxide) into the surrounding tissue and fluids even though it is covered by a thermodynamically stable oxide film [28,29]. An increase in oxide thickness, as well as incorporation of elements from the extra- cellular fluid (P, Ca, and S) into the oxide, has been observed as a function of implantation time [30]. Moreover, changes in the oxide stoichiometry, composition, and thickness have been associated with the release of titanium corrosion products in vitro [31]. Properties of the oxide, such as stoichiometry, defect density, crystal structure and orientation, surface defects, and impurities were suggested as factors determining biological performance [32,33].\nThe performance of titanium and its alloys in surgical implant applications can be evaluated with respect to their biocompatibility and capability to withstand the corrosive species involved in fluids within the human body [34]. This may be considered as an electrolyte in an electrochemical reaction. It is well documented that the excellent corrosion resistance of titanium materials is due to the formation of a dense, protective, and strongly-adhered film – which is called a passive film, as discussed before. Such a surface situation is referred to passivity or a passivation state. The exact composition and structure of the passive film covering titanium and its alloys is controversial. This is the case not only for the “natural” air oxide, but also for films formed during exposure to various solutions, as well as those formed anodically. The “natural” oxide film on titanium ranges in thickness from 2 to 7 nm, depending on such parameters as the composition of the metal and surrounding medium, the maximum temperature reached during the working of the metal, the surface finish, etc.\nOxides formed on Ti materials are varied with a general form; TiOX (1 \u003c x \u003c 2). Depending on x values, there are five different crystalline oxides; i.e., (1) cubic TiO (ao = 4.24 Å), (2) hexagonal Ti2O3 (ao = 5.37 Å, α = 56°48’), (3) tetragonal TiO2 (anatase) (ao = 3.78Å, co = 9.50 Å), (4) tetragonal TiO2 (rutile) (ao = 4.58 Å, co = 2.98 Å), and (5) orthorhombic TiO2 (brookite) (ao = 9.17 Å, bo = 5.43 Å, co = 5.13 Å). Besides these, there are (6) non-stoichiometric oxide (when x is not integral), and (7) amorphous oxides. It is widely believed that, among these oxides, only rutile and anatase type oxides are stable at normal conditions. Of interest, choice for rutile formation or anatase formation depends on the acidity of used electrolyte [8]. The rutile and anatase type oxides exibit different physical properties – interms of surface tension. Lim et al. [35] prepared various surface conditions on pure titanim and measured surface contact angles, surface electrochemical potential and roughness. It was found that the surface covered with only rutile type TiO2 was hydrophobic, whereas that covered with a mixture of rutile and anatase type of oxides showed hydrophilicity [35].\nThe level of neutrophil priming and activation following implant placement may be linked to the development and maintenance of long-term stability and osseointegration. Bisphosphonate effect on neutrophil activation was examined on differently treated surfaces [36]. Neutrophils were isolated from whole blood collected from healthy human donors, on a double dextran gradient. Treated surfaces were incubated with 5 × 105 neutrophils per curette. Luminol-dependent CL (chemiluminescence) was recorded for 60 min (priming or inflammatory phase), followed by secondary stimulation with 10−7 M phorbol myrisitate acetate at 60 min (activation phase) for a continuous CL measurement over 120 min. SEM evaluation was preformed. Results indicated that titanium surfaces which were covered with a mixture of rutile and anatase type TiO2 oxide films are capable of priming neutrophils, when compared to the acid-treated surface which was covered with rutile oxide only [36].\nUsing Auger Electron Spectroscopy (AES) to study the change in the composition of the titanium surface during implantation in human bone, observed that the oxide formed on titanium implants grows and takes up minerals during the implantation [30,37]. The growth and uptake occur even though the adsorbed layer of protein is present on the oxide, indicating that mineral ions pass through the adsorbed protein. It was shown that, using Fourier Transform Infrared Reflection Absorption Spectroscopy (FTIR-RAS), phosphate ions are adsorbed by the titanium surface after the protein has been adsorbed. Using x-ray photoelectron spectroscopy (XPS) [38], it was demonstrated that oxides on commercially pure titanium and titanium alloy (Ti-6Al-4V) change into complex phosphates of titanium and calcium containing hydroxyl groups which bind water on immersion in artificial saliva (pH = 5.2) [39]. It was shown that titanium is in almost direct contact to bone tissue, separated only by an extremely thin cell-free non-calcified tissue layer. Transmission electron microscopy revealed an interfacial hierarchy that consisted of a 20–40 nm thick proteoglycan layer within 4 nm of the titanium oxide, followed by collagen bundles as close as 100 nm and Ca deposits within 5 nm of the surface [40]. To reach the steady-state interface described, both the oxide on titanium and the adjacent tissue undergo various reactions. The physiochemical properties of titanium have been associated with the unique tissue response to the materials: these include the biochemistry of released corrosion products, kinetics of release and the oxide stoichiometry, crystal defect density, thickness and surface chemistry [41]. All these studies indicate that the surface oxide on titanium materials reacts with mineral ions, water, and other constituents of biofluids, and that these reactions, in turn, cause a remodeling of the surface.\nAs seen in the above, in general, the titanium passivating layer not only produces good corrosion resistance, but it seems also to allow physiological fluids, proteins, and hard and soft tissue to come very close and/or deposit on it directly. Reasons for this are still largely unknown, but it may have something to do with things such as the high dielectric constant for TiO2 (50 to 170 vs. 4–10 for alumina and dental porcelain), which should result in considerably stronger van der Waal’s bonds on TiO2 than other oxides; TiO2 may be catalytically active for a number of organic and inorganic chemical interactions influencing biological processes at the implant interface. The TiO2 oxide film may permit a compatible layer of biomolecule to attach [42,43]."}

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