Hydroxyapatite by Younes Sina


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Hydroxyapatite by Younes Sina, The University of Tennessee, MSE

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Hydroxyapatite by Younes Sina

  1. 1. Department of Materials Science & Engineering A review on Dental Ceramic: An analytical discussion about Hydroxyapatite, Chemistry and Processing By Younes Sina MSE560: Principles of Ceramic Processing Presented by Dr. Narendra B. Dahotre 1
  2. 2. Introduction Hydroxyapatite [Ca10 (PO4)6(OH) 2; abbreviated as HAp] is an inorganic compound whose chemical composition is similar to the composition of the bone. It is a very attractive material for biomedical applications such as a bone substitute material in orthopedics and dentistry due to its excellent biocompatibility, bioactivity and osteoconduction properties. HAp has been used extensively in medicine and dentistry for implant fabrication owing to its biocompatibility with human bone and teeth .However due to its poor mechanical properties, HAp ceramics cannot be used for heavy load bearing applications, but common uses include bone graft substitution and coatings on metallic implants. Biomaterials are a class of engineering materials which can be used in animal body tissue replacements, reconstructions, and regenerations, without any long term adverse effect. The development of biomaterials and manufacturing techniques broadened the diversity of applications of various biocompatible materials. Among the different classes of biomaterials, bioceramic is one of the promising classes of available biomaterials used as human body-implants. Few of the bioceramics have similarity with the mineral part of our bone; however do not match with the intricate structure of the bone. There are several calcium phosphate ceramics that are considered biocompatible. Of these, most are resorbable and will dissolve when exposed to physiological environments. Hydroxyapatite is the most important bioceramic materials for its unique bioactivity and stability. Unlike the other calcium phosphates, hydroxyapatite does not break down under physiological conditions.In fact; it is thermodynamically stable at physiological pH and actively takes part in bonebonding, forming strong chemical bonds with surrounding 2
  3. 3. bone. This property has been exploited for rapid bone repair after major trauma or surgery. While its mechanical properties have been found to be unsuitable for load- bearing applications such as orthopedics, it is used as a coating on load bearing implant materials such as titanium and titanium alloys or composites with other materials.[15] There are several methods to produce hydroxyapatite powder. The most popular and widely researched route is solution precipitation. HAp nanoparticles can be prepared using microwave irradiation. Solgel and hydrothermal routes are the two other important routes for HAp synthesis. Even HAp can be produced by mechanosynthesis route, in which case no heat treatment is required to produce crystalline nano HAp. Some other routes for synthesis of HAp are: Solid state reaction, plasma technique, hydrothermal hot pressing, ultrasonic spray pyrolysis, and emulsion system. Porous HAp is envisaged to have better biocompatibility, as tissues can grow much faster into the available pores. The pore size can be controlled and also complex shaped materials can be fabricated. Several efforts (specially processing routes) have been made to improve the mechanical properties of HAp. Thermal treatment is necessary to improve the mechanical properties. Even sometimes some amount of additives can be added to improve the sinterability and mechanical properties without affecting the bioactivity. Using Ca (OH) 2 additives the sintering temperature can be increased without any dissociation. [15] 3
  4. 4. Routes for synthesis HAp and modifying of its properties In this section of review it has been tried to introduce the most important routes for synthesis of HAp and methods for modifying of HAp’s properties. The objective is discussion about each method and comparison of their different parameters. Before that it is necessary to discuss about chemistry of HAp. Why chemistry of HAp is important? The composition, physicochemical properties, crystal size and morphology of synthetic apatites are extremely sensitive to preparative conditions. Furthermore the success and quality of orthopaedic coatings is also largely dependent upon the HA powder characteristics. For example spherical powders of narrow size distribution are favoured in order to enhance excellent heat transfer characteristics to increase deposition efficiency and decrease coating porosity. As we know synthetic HAp occurs in two structural forms, hexagonal and monoclinic, which have minor structural differences. The hexagonal HA form is usually formed by precipitation from supersaturated solutions at 25 °C to 100 °C and the monoclinic form of HA is primarily formed by heating the hexagonal form at 850 °C in air and then cooling to room temperature [22]. Although hydroxyapatite is considered as one of the potential materials for the replacement and reconstruction of human bone and teeth, and the biocompatibility of this material is well established, the main problem with this material is its reliability due its very poor mechanical properties. [15] 4
  5. 5. Hydroxyapatite is a thermally unstable compound, decomposing at temperatures from about 800-1200°C depending on its stoichiometry. The stoichiometry of hydroxyapatite is highly significant if thermal processing of the material is required.Calcium phosphate phases of alpha and beta-tricalcium phosphate, tetracalcium phosphate occur with slight imbalances in the stoichiometric ratio of calcium and phosphorus in HA from the molar ratio of 1.67. It is also important to know the close relation between the stoichiometry, acidity and solubility. Thus, it is known that the lower the Ca/P ratio and the larger the acidity of the environment, the higher will be the solubility of the HA. For Ca:P < 1, both acidity and solubility are extremely high, and both parameters decrease substantially for Ca/P ratios close to 1.67, which is the value of stoichiometric hydroxyapatite. The prevention of the formation of calcium phosphate phases with relatively higher solubility is significant when stability of hydroxyapatite is an important issue in the application. It is possible to sinter phase pure hydroxyapatite using stoichiometric composition at temperatures up to 1300 c. [4] One of the most important properties of HAp is prosity. The simplest way to generate porous scaffolds from ceramics such as HA is to sinter particles, preferably spheres of equal size. With the increase in temperature pore diameter decreases and mechanical properties increase as the packing of the spheres increases. Hot isostatic pressing can also be used to further decrease the pore diameter. During sintering porosity can be increased by adding fillers such as sucrose, gelatin, and PMMA microbeads to the powder and the wetting solution. One of the most reliable formulations is the use of an HA powder slurry with gelatin solution. Surface tension forces cause the formation of soft and spherical porous particles of HA and gelatin. It is 5
  6. 6. possible to produce porous bulk material with an interconnected pore structure with an average pore size of 100 microns after sintering. One other method for producing porous ceramics is freeze drying. Freeze drying process can be used to introduce aligned pores in the final ceramic structure but the generated pore diameters do not exceed 10 microns. The most important ways for synthesis of HAp is explained at follow: Wet chemical process (precipitation route) This route includes two major reactions: acid-base method and chemical precipitation. Acid-base method is known as one of the most favorable method in industry because the only it’s by- product is water. Temperature and PH in this route are very important factors for having a stable HAp. Increasing of temperature and maintaining PH at 6 affect on Ca/P ratio. Acid-base reaction can be written as: 10 Ca (OH) 2+6 H3 PO 4→Ca10 (PO 4)6 (OH) 2+18 H 2O The common precipitation reaction can be written as: 10Ca (NO3)2 + 6(NH 3) HPO +2 H2 O → Ca10 (PO4)6 (OH) 2 + 12NH4 NO3 +8 HNO3 In this reaction PH>10 is a necessary condition for a stable and stochiometric form of HAp. Precipitation reaction for synthesis nanostructure HAp can be written as: 6
  7. 7. 10CaCl2 + 6Na2PO4 + NaOH → Caq+(x/2) (PO4)6(OH)2 + (18+x) NaCl + (1-(x/2)) CaCl2 (x=0,1,2) Flowchart for the synthesis of the hydroxyapatite powder Reaction is completed during 24 hours at air. After a complete washing it is dried at 80 C for 24hours and then it is heated for 10 hours with rate of 5 min/C until 1000 C. PH should be maintained over 7. In these conditions, HAp powder size is less than 10 nm and with increasing of NaOH, the powder will be stable until 1000C at air. Wet chemical process, which is based on precipitation route, is the most convenient and commonly used process. This process is very simple and easy to use. The preparative reaction and the character of reaction products can be regulated easily. [12] 7
  8. 8. Hydrothermal route Hydrothermal process, which works at high temperature and high pressure, is also one of the widely used and earliest developed methods for the synthesis of hydroxyapatite. The process is not only an environmentally benign but also chemical composition and stoichiometry of the material can be controlled [12]. Hydrothermal synthesis has been used to transform slurries, solutions, or gels into the desired crystalline phase under mild reaction conditions typically below 350 oC. Typical powders synthesized by this method have been shown to consist of needle-like particles between 20 - 40 nm in diameter and 100-160 nm in length. The motivation for synthesizing HAp by hydrothermal means is to obtain nanosized particles for infiltration of dentinal tubules for the alleviation of hypersensitivity, a common problem for millions of children and adults worldwide. Single phase hydroxyapatite crystallites with a rod-like morphology were synthesized by a hydrothermal method at 200 oC under saturated water vapor pressure for 24 hrs from a precipitate formed by mixing Ca(NO3)2&4H2O, (NH4)2HPO4 and distilled water. Longer treatment times led to the production of a secondary phase, monetite, (CaHPO4). However the treatment time had no effect on the particle morphology or size within the reaction time range of 24-72 hrs. The crystallites were measured to be within the size range 100-600 nm in length and 10-60 nm in diameter. Early results indicate smaller, more or spherical particles may be desirable for dentine tubule infiltration. [7] Hydrothermal techniques give hydroxyapatite powders with a high degree of crystallinity and better stoichiometry having a wide distribution of crystal sizes. [4] 8
  9. 9. Microwave irradiation route Use of microwaves as an alternative energy source, due to its environment-friendly, non-polluting, clean and safe approach, is also one of the most promising and excellent approaches. The great potential offered by microwave irradiation process, is the acceleration of chemical reaction. [12] In this technique usually spray dried hydroxyapatite powder, synthesized through Solution-precipitation route,is used . The aim is to sinter hydroxyapatite at much lower temperature using microwave and also synthesizeing the material in such a heating schedule which can have better properties than conventional dense HAp. The most challenge part is to sinter HAp powder in a single stage (two segments) heating schedule without resort to calcinations procedure at higher (800C) temperature. Based on the sintering studies on solution precipitation spray dried HAp powders, the following conclusions can be drawn: a) In one segment sintering, a maximum density of ~97% can be obtained after sintering at 1100C for 3hrs in conventional sintering and density of ~99% obtained after microwave sintering at 1000C and 1100C for 0.5 hrs. But in this case samples can be cracked. b) However, lesser densification (~95%) is obtained in two segments sintering processes accomplished by intermediate isothermal holding at 800C followed by 9
  10. 10. sintering at 1200C. The samples cannot be cracked after sintered in conventional as well as microwave sintering. This 5% porosity may leads to more bioactivity. c) For conventional sintering, holding for 2hrs at 800C and subsequent sintering for 3hrs at 1200C result almost fully dense microstructure is characterized by equiaxed grains of 1-2μm size. d) The microwave sintering, can be performed by holding at 800C for 0.5 hrs and sintering at 1200C for 0.5 hrs also produce dense HAp of faceted grains of 1-2μm size. The microwave sintering is found to be a time and energy efficient densification technique in dendifying HAp. [15] Ultrasonic irradiation route Ultrasonic irradiation is a novel precipitation method for nanocrystalline HAp preparation. The chemical effects of ultrasound derive primarily from acoustic cavitations (the formation, growth and collapse of bubbles). Synthesis of HAp nanoparticles in ultrasonic precipitation and influence of temperature, [Ca2+], Ca/P ratio and ultrasonic power on its morphology and crystalline has been recently reported. In this method there is ability for HAp synthesizing using homogeneous precipitation method in the field of ultrasonic irradiation. Urea can act as an agent for precipitation. Basic parameters in this technique are: temperature, concentration, power of ultrasound field, time and dynamics of ultrasound field effect. [11] Application of ultrasound for the preparation of nano-sized PLGA/HAp (poly d,l lactide – co-glycolide) composite particles of spherical morphology has been reported. 10
  11. 11. Microscopy analysis results reveal that using the ratio 90 wt% of PLGA in relation to 10% HAp in the steps of synthesis in the field ultrasound highly uniform and spherical particles with diameter of 250-300 nm can be obtained. The presence of both PLGA and HAp in these particles can be confirmed by IR spectroscopy. [10] Sol-Gel technique Sol Gel technique has been developed and employed to prepare various materials because it has main advantage of easy control of chemical composition and low temperature synthesis that are very important for thin film formation.[21] The use of sol gel routes to form a bioactive hydroxyapatite layer on metal substrates has recently attracted in the biomedical field. The sol gel method represents the low temperature way of the production of glasses, ceramic and composite materials with better purity and homogeneity than high temperature conventional processes. This process has been used to produce a wide range of compositions (mostly oxides) in various forms, including powders, org/inorg hybrids, fibers, coating, thin films, monoliths and porous membranes. One of the most attractive features of the sol gel process is that it can produce compositions that cannot be created by the conventional methods. The mixing level of the solution is retained in the final product. In sol gel chemistry, the metal alkoxides convert to amorphous gels of metal oxides through hydrolysis and condensation reactions. Hydroxyapatite can be synthesized using the sol-gel route with proper heat and acid treatment. There will be no significant differences observed for the powder with and without alcohol medium excluding the pH and gelation time. Nowadays the sol-gel route is becoming a unique low-temperature technique to produce ultra fine and pure 11
  12. 12. ceramic powders. Recently, hydroxyapatite powders and coatings have been successfully synthesized by the sol gel method. The process parameters have been optimized to produce high purity hydroxyapatite. Fluorinated hydroxyapatite Fluorinated hydroxyapatite(FHAp) [Ca10(PO4)6(OH)2-2xF2x (0 ≤ x ≤ 1)], where F partially replaces OH in hydroxyapatite, is potentially a very interesting biomaterial. It was suggested that fluoride-substituted hydroxyapatite has a better thermal and chemical stabilities than hydroxyapatite. [6] FHA exhibits a very attractive combination of stability and biocompatibility. However, it has been reported that if all of the OH groups in HA are replaced by F to form fluorapatite (FA), the resulting material is not osteo-conductive. Moreover, the high F content might lead to severe adverse effects such as osteomalacia . As a result, various methods have been developed in an attempt to tailor the fluorine content of FHA to achieve the best biological properties. FHA can be either prepared using a solid-state reaction or a wet-chemical process, but the later is used more commonly. There are several methods of synthesizing fluoridated hydroxyapatite with varied fluorine contents, such as, by sol-gel, a solid state reaction, and pyrolysis methods. The pH-cycling method as the modified wet chemical process was first introduced to avoid a high temperature operation and the use of volatilized alcohol (fluorine containing reagent). Fluorhydroxyapatite is synthesized through a pH-cycling method by varying sodium fluoride (NaF) concentration in hydroxyapatite suspension as a modified wet-chemical process. Synthesized fluorhydroxyapatite powder has been characterized on a 12
  13. 13. macroscopic level by XRD, FTIR and chemical analysis (AAS, EDTA titration technique and F-selective electrode), while SEM has provided detailed information at the microscopic (individual grain) level. The XRD analysis has showed that the fluorhydroxyapatite sample prepared is nearly pure fluorhydroxyapatite. Only low levels of specific impurities (such as CaO) have detected and it is also demonstrated that the crystallites of FHA were nanosize. FTIR investigations also have showed all the typical absorption characteristics of fluorhydroxyapatite. Chemical analyses (for example AAS and EDTA titration and F-selective electrode analysis) are used for the determination of Ca/P molar ratio and calculation of the replaced fluorine content in the crystalline network of hydroxyapatite. The bulk Ca/P ratio has determined as 1.71 which showes the measured Ca/P ratio for the synthesized powder is higher than stoichiometric ratio (1.667) which is expected for a pure HA (or FHA) phase. Also According to the F- selective electrode analysis result and calculations performed, the achieved formula of the synthesized fluorhydroxyapatite is Ca10 (PO4)6(OH) 0.7F1.3. Finally, the SEM technique ascertained that the particles of prepared powder are rod-like. [6] 13
  14. 14. Flowchart for the synthesis of the fluorinated hydroxyapatite powder [6] Discussion Now after being familiar with different routes of synthesizing of HAp and its derivatives, we can discuss about the advantages and disadvantages of each process. Some parameters that are determiner are: Time, economic, porosity, density, environmental consideration, particle size, morphology, homogeneity, ability of sintering, purity, Ca/P ratio, and ease of control. Precipitation method: HA may be synthesized by various methods, including the sol- gel technique, solid-state reactions at elevated temperatures, chemical precipitation and biosynthesis routes. The precipitation method appears more favorable due to its 14
  15. 15. simplicity, cost effectiveness and its non-polluting nature (that is, its only by -product is water). The success and quality of orthopedic coatings is largely dependent upon the HA powder characteristics. These include phase composition, crystallinity, particle size and powder morphology .Spherical powders of narrow size distribution are favored in order to enhance excellent heat transfer characteristics to increase deposition efficiency and decrease coating porosity. Microwave and hydrothermal: Microwave and hydrothermal routes yield uniform grain growth along with highly porous crystalline HAp material. The microwave irradiation process requires less time for the synthesis of hydroxyapatite compared to other processes. The grain size is found to be in the range 31–54 nm. The dielectric constant is in the range 9–13. Hydroxyapatite seems to be a potential candidate to act as CO sensor at an optimum temperature near 125°C. The Ca/P ratio is in the range of 1.6– 1.7, a property which is important in biomedical applications. The dielectric constant for all the samples is found to be at 400 Hz, in the range 9–13. It is reported in the literature that the dielectric constant of HAp at 291.5 K was 15.4 at 100 Hz. The difference in the values can be attributed to the difference in the processing and structure of the end product [15]. The dielectric behavior of monoclinic HAp as a function of temperature, showing the phase change from monoclinic to hexagonal at a temperature of 483 K is already reported. [12] Wet chemical route: The HAp grown at room temperature, via wet chemical route, shows non-uniform agglomerates wherein there is large variation in particle sizes. [12] Microwave sintering: Densification studies of normal pressureless sintered and Microwave sintered has been carried out. In all cases, Microwave sintered samples 15
  16. 16. showed higher density than normal pressureless sintered samples, when sintered at the same temperature. It can be noted that the soaking time in case of conventional sintering is six times longer than microwave sintering. It shows that using microwave the sintering temperature and time can be reduced a greater extent. Sintering of crack free body was a big challenge for this material. Calcined at 300 C and 350 C powder always contained some amount of moisture. At higher temperature this moisture creates stress and the sample get fractured, although the densities of the fractured parts were good enough. It has reported that calcining at 800 C gives good results, but still problem persists during pressing of calcined powders. In this case, the green pellets of spray dried powders were soaked at 800 C for 2 hrs in case of normal pressureless sintering and for 30 min in case of microwave sintering. At 800 C moisture goes out creating some channels in the grain boundary regions. These channels create 5% porosity of final products.[15] Conventional methods (wet, dry and hydrothermal routes): the conventional methods (wet, dry and hydrothermal routes) of preparation of this important bioceramic material are tedious and time consuming. For example, in one process HAp was precipitated from aqueous solutions using appropriate amounts of calcium nitrate and di-ammonium hydrogen phosphate using NH4OH to maintain high pH value and the mixture was kept stirred for about 2 h, later centrifuged and the product was allowed to ripen. In another method solid state mixture of tri- and tetracalcium phosphates had to be heated for several hours at 1283 K in a current of moist air to produce HAp. In yet another process described a hydrothermal route for the synthesis of HAp in which dicalcium phosphate was heated with water at 573 K for 10 days in a platinum lined 16
  17. 17. hydrothermal bomb. There is thus great need to develop an efficient route to synthesize HAp. Microwave irradiation routes: Recently novel microwave irradiation routes have been developed for the synthesis of inorganic materials. Products with good structural uniformity and crystallinity have been obtained in these microwave methods. In this communication a simple and fast precipitation method is described for the preparation of hydroxyapatite in which microwave irradiation has been used. [2] Sol Gel technique: Sol Gel technique has been developed and employed to prepare various materials because it has main advantage of easy control of chemical composition and low temperature synthesis that are very important for thin film formation [21]. Traditionally, this bioceramic, Ca10 (PO4)6(OH) 2, can be synthesized by solid state reactions, plasma techniques, hydrothermal hotpressing, and many wet chemical precipitation and mechano-chemical methods. In wet precipitation method, the chemical reactions take place between calcium and phosphorus ions under a controlled pH and temperature of the solution. The precipitated powder is typically calcined at high temperature in order to obtain a stoichiometric apatitic structure. Slow titration and diluted solutions must be used to improve chemical homogeneity and stoichiometry within the system. Careful control of the solution condition is also required in the wet precipitation methods. In early reports, the decrease of solution pH below about 9 could 17
  18. 18. lead to the formation of Ca-deficient apatite structure. In some cases, a well-crystallized HA phase was only developed while approaching a calcination temperature of 1200oC. The sol-gel approach provides significantly easier conditions for the synthesis of HA. Sol-gel synthesis of HA ceramics has recently attracted much attention. Sol-gel process refers to a low-temperature method using chemical precursors that can produce ceramics and glasses with better purity and homogeneity. This process is becoming a common technique to produce ultra fine and pure ceramic powders, fibers, coatings, thin films, and porous membranes. Compare to the conventional methods, the most attractive features and advantages of sol-gel process include (a) molecular-level homogeneity can be easily achieved through the mixing of two liquids; (b) the homogeneous mixture containing all the components in the correct stoichiometry ensures a much higher purity; and, (c) much lower heat treatment temperature to form glass or polycrystalline ceramics is usually achieved without resorting to a high temperature. More recently, the sol-gel method has been extensively developed and used in biotechnology applications. [21] Important parameters in synthesizing of HAp 18
  19. 19. In previous part we compared the different routes of HAp synthesizing and we discussed about some parameters that differ depend on the route. In fact only few parameters between them are more important. For example ease of reaction, controlling of PH and temperature, time, even though economical and environmental consideration are not basic than porosity, particle size, and sintering ability. Therefore here we pay an especial and detailed view to the most vital parameters in production of HAp. Porosity While porous materials have many important applications in, for example, acoustic and thermal insulation, transportation, filtration, purification, biomaterials, building constructions, a new generation of porous biomaterials has recently emerged enabling one to better reproduce the structure of natural bone. Several groups have been successful in controlling the size, volume, and interconnectivity of pores in their materials. Nevertheless, there have been only a few reports on the use of porous materials for dental fillings: a possible reason for this is that porous materials tend to have poor mechanical properties, while the mastication process produces high compression and shear stresses that must be supported by the obturation material. Consequently, nonporous materials, usually hard polymer resins, are more commonly used to support these stresses. However, by the selection of an appropriate agglutinating polymer (for a ceramic filler), it is possible to create porous materials with suitable morphology and mechanical strength. Beyond achieving the correct morphology, a successful dental obturation material must be chemically compatible with and adhere to the substrate. Many obturation materials are designed essentially by controlling only mechanical properties because adding a ceramic, or generally a filler, is 19
  20. 20. known to improve the mechanical properties of polymers. Here, we should take into account morphology, chemical structure, mechanical behavior, and surface properties, considering the combined effect of all of these on tooth ingrowth, as well as the role of viscoelasticity for implant compliance and performance. Because teeth constitute an organic–inorganic hybrid, a reliable hybrid for dental applications should contain an agglutinating polymer that possesses: (i) high shear strength (around 70 MPa) resistance interfacial stresses during mastication; (ii) appropriate tensile/ compressive strength and toughness, because very rigid and tough materials may lead to premature wear of the real teeth from contact during chewing; (iii) high scratch resistance, to avoid the occurrence of fissures, cracks, or canals that invite bacterial growth; (iv) good adhesion with the hydroxyapatite (HAp) powder particles and with the substrate (dentin) to avoid microfiltration, which produces bacterial growth; (v) high hydrolytic stability for durability within the environmental conditions of the mouth; and (vi) appropriate chemistry, to favor nonaggravating molecular recognition by the immune system. For all composites of the general type polymer plus ceramic, the problem of adhesion between differing components is an important challenge in product development. In turn, adhesion depends on surface and interfacial tension values.[5] Particle size Materials based on calcium hydroxyapatite (HAp) are finding wide application in medicine for creating bone implants and carriers of medicines, for filling chromatographic columns, as adsorbents, and so forth. Various chemical methods are used to obtain high-quality powders of calcium phosphates, including HAp. The most popular methods are chemical co-precipitation from water solutions containing the ions 20
  21. 21. Ca2+, (PO4)3- , and (OH)–, which, interacting with pH > 7, form primary crystallites of insoluble HAp. The process of obtaining powder for ceramics includes chemical interaction between the initial components, separating and drying the precipitate, and disaggregating the dried product. A great deal of attention is now being devoted to obtaining nanopowders, i.e., powders with particle sizes not exceeding 100 nm. However, the use of such powders for obtaining ceramic remains problematic. Nanopowders have a high specific surface area and therefore excess surface energy — the driving force of the sintering process. Obtaining ceramic with uniform structure from nanopowders is a quite difficult problem. Nanoparticles aggregate, and the average particle size (aggregates) in the powder is 1 – 3μ m. It is such aggregates that play the determining role in the formation of the microstructure of ceramic. The use of chemical synthesis to obtain HAp powder with individual particle sizes less than 100 nm results in the formation of 1 – 15 μm grains, depending on the sintering regime and the method used to prepare the power. An obvious way out of the technological situation which has developed is to use a number of techniques that make it possible to decrease the aggregation of the powder material at different stages. One such technique is to use surfactants, which modify the surface of particles, and to eliminate milling of the powder material, assuming formation from highly concentrated suspensions. A number of other techniques can also be used. The use of various surfactants is well known for obtaining oxide nanoparticles or particles with intricate shapes. However, in most cases, the influence of the surfactants or other soluble high-molecular compounds (HMC) used in synthesis on the behavior of powder material during formation of a ceramic is not studied. The use of gelatin or polyvinyl alcohol (PVA) in the synthesis of oxide powders 21
  22. 22. is well known. However, in these cases HMC can be used in substantial quantities to perform synthesis in a viscous medium, where the mobility of the components is decreased. Polyvinyl alcohol is a widely used substance in the technology of technical ceramics based on pure oxides (containing no other components) that give plasticity to the forming paste and ensure consolidation of material at the formation stage. Polyvinyl alcohol meets all requirements for an ideal temporary technological binder: chemically inert, nontoxic, including at the decomposition stage, completely removed during calcination before the sintering starts for most oxide materials. [18] Homogeneity The increase in density is considered to be due to increase in the homogeneity in the matrix phase and the lower sintering temperature of hydroxyapatite. With increase in temperature other phases contribute to the increase in density by enhanced sintering. [4] Goal 1) For tooth and bone implants, a primary requirement is that the material be bioaccepted, because vascularization requires the material to support cellular activity without eliciting an inappropriate host response on recognition of the foreign molecules (i.e., molecular recognition). Second, the morphology must be suitable to allow vascularization and attachment to the existing bone or tooth substrates. Morphological specifications for bone-implant materials require a pore size in the range of 100–400 μm, with the pores being interconnected and comprising a volume fraction between 50% and 70%. For tooth implants, on the other hand, the mean optimal pore size is 2.90 22
  23. 23. ± 0.22 μm (standard deviation), which is considerably smaller. A precise densitometry study showed that enamel has a density distribution that is narrower with respect to that of dentin: namely, the density of enamel is reportedly between 2.49 and 3.00 g/mL (mean density 2.94 ± 0.03 g/mL), while the density of dentin is between 2.06 and 2.24 g/mL (mean density 2.14 ± 0.01 g/mL). Using these values, it is possible to demonstrate that the pore volume fraction of dentin is around 27%, a value in good agreement with that of 22%, which was obtained using results that have been reported elsewhere.8 One observes then that pore size and pore volume fraction are smaller for dentin than for bone.[5] 2) Metallic biomaterials, such as titanium and its alloys, have enjoyed clinical successes because of their superior strength, durability, corrosion resistance in physiological environment, biocompatibility and bioinductibility. The high mechanical strength and toughness of these biometals are the most important advantages over bioactive hydroxyapatite (HAp) ceramics. Therefore, a system that combines both materials has the mechanical advantages of the underlying (metallic) substrate and biological affinity of the HAp surface to natural tissue. 3) In the development of new engineering materials, apart from other required properties, strong and stiff materials coupled with reasonable ductility are always targeted. In developing new biomaterials for tissue replacement, the structure and properties of the tissue which is to be replaced must be taken into consideration, because, if properties of the new material are significantly different from those of the host tissue, the material under development will cause dynamic changes in the host 23
  24. 24. tissue after implantation, as has been discussed in terms of Wolff’s Law, and thus will not achieve the goals considered in the original conceptual design. [4] Wolff’s Low: If a stiff metal or ceramic implant is placed in the bone, the bone will be subjected to lower mechanical stresses, and consequently bone will resorb. [14] What should be done? Major drawbacks of all biocompatible ceramics restrict their use in biomedical applications to some degree. Low strength and fracture toughness of hydroxyapatite limits its bulk use in many implants. As ZrO2 ceramic is a bioinert material, it does not directly bond with natural bone in hip-joint replacement. Alumina’s high elastic modulus causes stress shielding those results in loosening of implants in patients with osteoporosis. The preparation of a microscale composite material is a promising idea for improving the mechanical properties of hydroxyapatite. HA may be reinforced with 24
  25. 25. other ceramics or metals in the form of powders, platelets, or fibers. This approach has been the subject of extensive study since the successful development of ceramic-matrix composite materials. In order to synthesize an effective ceramic-matrix composite material, three conditions should be satisfied. The strength and the stiffness of the reinforcement must exceed those of the matrix. Along with this requirement the strength of the interfacial layer between the matrix and the reinforcement should be appropriate with limited reaction between the matrix and the reinforcement producing bond strength neither too weak nor too strong. Also, the difference between the coefficients of thermal expansion of the phases should be low enough to prevent formation of microcracks during cooling. The absence of these conditions provides microstructural defects resulting in deterioration of the mechanical properties of the composite. The biocompatibility of the reinforcement phase should also be considered when the ceramic matrix composite is designed to be involved in biomaterials applications. Most metals react with the HA to form metal oxides and tricalcium phosphate (TCP, Ca3 (PO4)2) or tetracalcium phosphate (TeCP, Ca4 (PO4)2O), leading to a serious reduction in the biocompatibility of HA. Partially stabilized zirconia has been commonly used as reinforcement for many ceramics because of its high strength and fracture toughness. Bioinertness is another merit of the ZrO2. However, extensive reaction between the HA and the ZrO2 to form TCP and fully stabilized ZrO2 is a big disadvantage of this approach. Alumina, which is also classified as a bioinert material, has been widely investigated as a reinforcing agent for HA. When large alumina platelets were added, the fracture toughness of the HA increased without excessive reaction between the HA and the Al2O3. However, the improvement in strength was 25
  26. 26. minimal because of the formation of microcracks around the platelets due to the large difference in coefficient of thermal expansion between Al2O3 and HA. On the other hand, when fine Al2O3 powder was used, the formation of the microcracks was circumvented; however, the improvement in mechanical properties was limited due to relatively low mechanical properties of the Al2O3 itself . Therefore, it is desirable to combine the advantages of both materials as reinforcements for the HA: the excellent mechanical properties of ZrO2 and the chemical inertness of Al2O3 with respect to the HA. [4] Physical properties of HAp, Alumina, and Zirconia have been showed in the following tables: [4] a) Typical Mechanical Properties of Dense Hydroxyapatite Ceramics Theoretical density 3.156 g/cm3 Hardness 500-800 Vickers, 2000-3500 Knoop Tensile strength 40-100 MPa Bend strength 20-80 MPa Compressive strength 100-900 MPa Fracture toughness approx. 1 MPa/m1/2 Young’s modulus 70-120 GPa b) Mechanical properties of biomedical grade alumina Density 3.97 g/cm3 (99.9% Al2O3) Hardness 2200 Vickers Bend strength 500 MPa Compressive strength 4100 MPa Fracture toughness 4 MPa/m1/2 Young’s modulus 380 GPa Thermal expansion coefficient 8x10-6 1/K c) Mechanical properties of zirconia TZ-3Y Density 6.05 g/cm3 26
  27. 27. Hardness 1200 HV Bend strength 900-1200 MPa Compressive strength 2000 MPa Fracture toughness 7-10 MPa/m1/2 Young’s modulus 210 GPa Thermal expansion coefficient 11x10-6 1/K d) Mechanical properties of a compact human bone Test direction related to bone axis Parallel Normal Tensile strength (MPa) 124-174 49 Compressive strength (MPa) 170-193 133 Bending strength (MPa) 160 Shear strength (MPa) 54 Young’s modulus (GP)a) 17.0-18.9 11.5 Work of fracture (J/m2) 6000 KIc (MPa*m1/2) 2-12 Ultimate tensile strain 0.014-0.031 0.007 Ultimate compressive strain 0.0185-0.026 0.028 Yield tensile strain 0.007 0.004 Yield compressive strain 0.010 0.011 The ideal artificial bone demands good biocompatibility without the possibility of inflammation or foreign body/toxic reactions. Strong bonding with the host bone, active bone ingrowth into the graft, and bioabsorbability are also required. Sufficient strength to resist the mechanical load in the implanted bone is also needed. None of the biomaterials that have been developed unill now meet all of these criteria. HA has good biocompatibility and osteoconductivity, however its fragility is a drawback like most ceramic materials. Therefore, it can be used alone in areas that do not require good mechanical strength. It can also be used with supplementary metal fixation in areas which bear large amounts of the mechanical load. The structure of the dense sintered body is stronger and more able to bond rapidly with host bone, but its use is limited due to its high level of brittleness and low osteoconductivity and absorbability. Porous HA is considered a good substitute, because it shows good osteoconduction and is replaced 27
  28. 28. by the host bone although it is mechanically weak. Patterns of osteoconduction for porous HAs vary with pore configuration. In HA, the 50 micron sized pore is enough, and the 300 micron sized pore is optimum for osteoconduction. Porous HA can be a useful graft material due to its osteoconductivity and the ease with which its pore geometry can be controlled. The simplest way to generate porous scaffolds from ceramics such as HA is to sinter particles, preferably spheres of equal size. With the increase in temperature, pore diameter decreases and mechanical properties increase as the packing of the spheres increases. Hot isostatic pressing can also be used to further decrease the pore diameter. During sintering porosity can be increased by adding fillers such as sucrose, gelatine, and PMMA microbeads to the powder and the wetting solution. One of the most reliable formulations is the use of an HA powder slurry with gelatine solution. Surface tension forces cause the formation of soft and spherical porous particles of HA and gelatine. It is possible to produce porous bulk material with an interconnected pore structure with an average pore size of 100 microns after sintering. It is possible to produce interconnected pores with diameters up to 300 microns by using the polymer foam replication method. Open celled polyurethane foams can be immersed in ceramic slurries under vacuum to allow the slurry to penetrate into the pores of the foam. Burn out of foam at 250 °C produces the ceramic replica of the foam. Using a similar method hydroxyapatite coated zirconia scaffolds with interconnected pore diameters up to 500 microns have been produced. Zirconia’s enhanced strength allows a high percentage of porosity in the composite.[4] However some scientists believe because of poor thermal stability in HAp as indicated by the decomposition into other phases such as tricalcium phosphate (TCP; Ca3 28
  29. 29. (PO4)2) at sintering temperatures higher than 900 oC, this phase impurity often results in undesirable fast dissolution rates in vivo. The lack of commercially efficient techniques in processing pure HA ceramics to full densification without decomposition has somewhat restricted the wider applications of HA ceramics. In contrast, it is expected that fluorapatite (Ca5 (PO4)3F) or fluorhydro- xyapatite might have superior mechanical properties when sintered at high temperatures because of their higher thermal stability than HA. [19] References 1. A.Nakahira, S.Konishi, F.Nishimura, T.Murakami, Y.Honda, C.Karatan, M. Tamai, H. Aritani, Local structure of bioactive hydroxyapatite with solid solution of cation by XAFS, http://www.uvsor.ims.ac.jp/activity/AR2002/research%EF%BC%95/nakahira.pdf 2. B. Vaidhyanathan, K. Jrao, Rapid microwave assisted synthesis of hydroxyapatite, Bull. Mater. Sci., Vol. 19, No. 6, December 1996, pp. 1163-I 165 .3. E. B.Kenney, Overview of Periodontal Regenerative Surgery, www.dent.ucla.edu/pic/ppt/Regenerative-Surgery.ppt 4. E. Sahin, Synthesis and characterization of hydroxyapatite-alumina-zirconia biocomposites,september 2006, http://library.iyte.edu.tr/tezler/master/malzemebilimivemuh/T000548.pdf 5. H. E. Hagg Lobland, L. Hoang, J. R.Rodriguez, S.Vargar, 29
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  32. 32. 21. U. Vijayalakshmi,S. Rajeswari , Preparation and Characterization of Microcrystalline Hydroxyapatite Using Sol Gel Method , Trends Biomater. Artif. Organs, Vol. 19(2), pp 57-62 (2006) http://www.sbaoi.org 23 .Z. M. Markovic, B. O. Fowler, M.S. Tung, Preparation and Comprehensive Characterization of a Calcium Hydroxyapatite, Reference Material, Journal of Research of the National Institute of Standards and Technology, Volume 109, Number 6, November-December 2004 32