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Dorozhkin, S.V. Calcium Orthophosphate-Based Bioceramics. Encyclopedia. Available online: (accessed on 21 June 2024).
Dorozhkin SV. Calcium Orthophosphate-Based Bioceramics. Encyclopedia. Available at: Accessed June 21, 2024.
Dorozhkin, Sergey V.. "Calcium Orthophosphate-Based Bioceramics" Encyclopedia, (accessed June 21, 2024).
Dorozhkin, S.V. (2022, September 28). Calcium Orthophosphate-Based Bioceramics. In Encyclopedia.
Dorozhkin, Sergey V.. "Calcium Orthophosphate-Based Bioceramics." Encyclopedia. Web. 28 September, 2022.
Calcium Orthophosphate-Based Bioceramics

Various types of materials have been traditionally used to restore damaged bones. In the late 1960s, a strong interest was raised in studying ceramics as potential bone grafts due to their biomechanical properties. A short time later, such synthetic biomaterials were called bioceramics. During the past, there have been a number of important achievements in this field. Namely, after the initial development of bioceramics that was just tolerated in the physiological environment, an emphasis was shifted towards the formulations able to form direct chemical bonds with the adjacent bones. Afterwards, by the structural and compositional controls, it became possible to choose whether the CaPO4-based implants would remain biologically stable once incorporated into the skeletal structure or whether they would be resorbed over time. At the turn of the millennium, a new concept of regenerative bioceramics was developed, and such formulations became an integrated part of the tissue engineering approach. Now, CaPO4-based scaffolds are designed to induce bone formation and vascularization. These scaffolds are usually porous and harbor various biomolecules and/or cells.

calcium orthophosphates hydroxyapatite tricalcium phosphate

1. Bioceramics of CaPO4

1.1. History

The detailed history of HA and other types of CaPO4, including the subject of CaPO4 bioceramics, as well as description of their past biomedical applications, might be found elsewhere [1][2], where the interested readers are referred. One should just note that the earliest book devoted to CaPO4 bioceramics was published in 1983 [3].

1.2. Chemical Composition and Preparation

Currently, CaPO4 bioceramics can be prepared from various sources [4][5][6][7][8][9][10][11][12][13]. Nevertheless, up to now, all attempts to synthesize bone replacement materials for clinical applications featuring the physiological tolerance, biocompatibility, and a long-term stability have had only relative success; this clearly demonstrates both the superiority and a complexity of the natural structures [14].
In general, a characterization of CaPO4 bioceramics should be performed from various viewpoints such as the chemical composition (including stoichiometry and purity), homogeneity, phase distribution, morphology, grain sizes and shape, grain boundaries, crystallite size, crystallinity, pores, cracks, surface roughness, etc. From the chemical point of view, the vast majority of CaPO4 bioceramics are based on HA [15][16][17][18][19], both types of TCP, and various multiphasic formulations thereof [20]. Biphasic formulations (commonly abbreviated as BCP–biphasic calcium phosphate) are the simplest among the latter ones. They include β-TCP + HA [21][22][23][24][25][26][27][28][29], α-TCP + HA [30][31][32], and biphasic TCP (commonly abbreviated as BTCP), consisting of α-TCP and β-TCP [33][34][35][36][37][38]. In addition, triphasic formulations (HA + α-TCP + β-TCP) have been prepared as well [39][40][41][42]. Further details on this topic can be found in a special research [20]. Leaving aside a big subject of DCPD-forming self-setting formulations [43][44], one should note that just a few publications on bioceramics prepared from other types of CaPO4 are available.
The preparation techniques of various types of CaPO4 have been extensively research in the literature [45][46][47][48][49][50], where the interested readers are referred. Briefly, when compared to both α- and β-TCP, HA is a more stable phase under the physiological conditions, as it has a lower solubility and, thus, slower resorption kinetics [51][52][53]. Therefore, the BCP concept is determined by the optimum balance of a more stable phase of HA and a more soluble TCP. Due to a higher biodegradability of the α- or β-TCP component, the reactivity of BCP increases with the TCP/HA ratio increasing. Thus, in vivo bioresorbability of BCP can be controlled through the phase composition [22]. Similar conclusions are also valid for the biphasic TCP (in which α-TCP is a more soluble phase), as well as for both triphasic (HA, α-TCP, and β-TCP) and yet more complex formulations [20].
As implants made of sintered HA are found in bone defects for many years after implantation, bioceramics made of more soluble types of CaPO4 are preferable for the biomedical purposes. Furthermore, the experimental results showed that BCP had a higher ability to adsorb fibrinogen, insulin, or type I collagen than HA [54]. Thus, according to both observed and measured bone formation parameters, CaPO4 bioceramics have been ranked as follows: low sintering temperature BCP (rough and smooth) ≈ medium sintering temperature BCP ≈ TCP > calcined low sintering temperature HA > non-calcined low sintering temperature HA > high sintering temperature BCP (rough and smooth) > high sintering temperature HA [55]. This sequence was developed in the year 2000 and, thus, neither multiphase formulations nor other CaPO4 are included.

1.3. Forming and Shaping

In order to fabricate CaPO4 bioceramics in progressively complex shapes, scientists are investigating the use of both old and new manufacturing techniques. These techniques range from an adaptation of the age-old pottery techniques to the newest manufacturing methods for high-temperature ceramic parts for airplane engines; namely, reverse engineering [56][57] and rapid prototyping [58][59][60] technologies have revolutionized a generation of physical models, allowing the engineers to efficiently and accurately produce physical models and customized implants with high levels of geometric intricacy. Combined with computer-aided design and manufacturing (CAD/CAM), complex physical objects of the anatomical structure can be fabricated in a variety of shapes and sizes. In a typical application, an image of a bone defect in a patient can be taken and used to develop a three-dimensional (3D) CAD computer model [61][62][63][64][65]. Then, a computer can reduce the model to slices or layers. Afterwards, 3D objects and coatings are constructed layer-by-layer using rapid prototyping techniques. The examples comprise fused deposition modeling [66][67], selective laser sintering [68][69][70][71][72][73], laser cladding [74][75][76][77], 3D printing and/or plotting [78][79][80][81][82][83][84][85], robocasting [86][87][88], solid freeform fabrication [89][90][91][92][93][94], stereolithography [95][96][97][98], and direct light processing [99]. More advanced techniques, such as 4D [100][101] and 5D [102] printing techniques, have been introduced as well. Three-dimensional printing of the CaPO4-based self-setting formulations is known as well [83]. Additional details of these techniques are available in the literature [103][104][105][106].
In addition to the aforementioned modern techniques, classical forming and shaping approaches are still widely used. The selection of the desired technique depends greatly on the ultimate application of the bioceramic device, e.g., whether it is for a hard-tissue replacement or an integration of the device within the surrounding tissues. In general, three types of processing technologies might be used: (1) employment of a lubricant and a liquid binder with ceramic powders for shaping and subsequent firing; (2) application of self-setting and self-hardening properties of water-wet molded powders; (3) materials are melted to form a liquid and are shaped during cooling and solidification [107][108][109]. Since CaPO4 are either thermally unstable (MCPM, MCPA, DCPA, DCPD, OCP, ACP, CDHA) or have a melting point at temperatures exceeding ~1400 °C with a partial decomposition (α-TCP, β-TCP, HA, FA, TTCP), only the first and the second consolidation approaches are used to prepare bulk bioceramics and scaffolds. The methods include uniaxial compaction [86][110][111], isostatic pressing (cold or hot) [28][112][113][114][115][116][117][118], granulation [119][120][121][122][123][124][125], loose packing [126], slip casting [127][128][129][130][131][132][133], gel casting [95][134][135][136][137][138][139], pressure mold forming [140][141][142], injection molding [143][144][145][146], polymer replication [147][148][149][150][151][152][153][154], ultrasonic machining [155], extrusion [156][157][158][159][160][161][162], and slurry dipping and spraying [163]. In addition, to form ceramic sheets from slurries, tape casting [135][164][165][166][167][168], doctor blade [169], and colander methods can be employed [107][108][109]. In addition, flexible, ultrathin (of 1 to several microns thick), freestanding HA sheets were produced by a pulsed laser deposition technique, followed by thin film isolation technology [170]. Various combinations of several techniques are also possible [135][171][172][173][174]. Furthermore, some of those processes might be performed under the electromagnetic field, which helps crystal aligning [129][132][175][176][177][178]. Finally, the prepared CaPO4 bioceramics might be subjected to additional treatments (e.g., chemical, thermal, and/or hydrothermal ones) to convert one type of CaPO4 into another one [154].
To prepare bulk bioceramics, powders are usually pressed damp in metal dies or dry in lubricated dies at pressures high enough to form sufficiently strong structures to hold together until they are sintered [179]. An organic binder, such as polyvinyl alcohol, helps to bind the powder particles altogether. Afterwards, the binder is removed by heating in air to oxidize the organic phases to carbon dioxide and water. Since many binders contain water, drying at ~100 °C is a critical step in preparing damp-formed pieces for firing. Too much or too little water in the compacts can lead to blowing apart the ware on heating or crumbling, respectively [107][108][109][113]. Furthermore, removal of water during drying often results in subsequent shrinkage of the product. In addition, due to local variations in water content, warping and even cracks may be developed during drying. Dry pressing and hydrostatic molding can minimize these problems [109]. Finally, the manufactured green samples are sintered.
It is important to note that forming and shaping of any ceramic products require a proper selection of the raw materials in terms of particle sizes and size distribution; namely, tough and strong bioceramics consist of pure, fine, and homogeneous microstructures. To attain this, pure powders with small average size and high surface area must be used as the starting sources. However, for maximum packing and least shrinkage after firing, mixing of ~70% coarse and ~30% fine powders have been suggested [109]. Mixing is usually carried out in a ball mill for uniformity of properties and reaction during subsequent firing. Mechanical die forming or sometimes extrusion through a die orifice can be used to produce a fixed cross-section.
Finally, to produce the accurate shaping, necessary for the fine design of bioceramics, machine finishing might be essential [63][107][180][181]. Unfortunately, cutting tools developed for metals are usually useless for bioceramics due to their fragility; therefore, grinding and polishing appear to be the most convenient finishing techniques [63][107]. In addition, the surface of CaPO4 bioceramics might be modified by various supplementary treatments [182][183], and CaPO4 bioceramics might be subjected to post-processing actions, such as immersing into special solutions [184].

1.4. Sintering and Firing

After being formed and shaped, the CaPO4 bioceramics are commonly sintered. A sintering (or firing) procedure is a thermal process in which loosely bound particles are converted into a consistent solid mass under the influence of heat and/or pressure without melting the particles. This process is of great importance to manufacture bulk bioceramics with the required mechanical properties. Usually, this technique is carried out according to controlled temperature programs of electric furnaces in adjusted ambience of air with necessary additional gasses; however, always at temperatures below the melting points of the materials. The firing step can include temporary holds at intermediate temperatures to burn out organic binders [107][108][109]. The heating rate, sintering temperature, and holding time depend on the starting materials. For example, in the case of HA, these values are in the ranges of 0.5–3 °C/min, 1000–1250 °C, and 2–5 h, respectively [185]. In the majority of cases, sintering allows a structure to retain its shape. However, this process might be accompanied by a considerable degree of shrinkage [186][187][188], which must be accommodated in the fabrication process. For instance, in the case of FA sintering, a linear shrinkage was found to occur at ~715 °C and the material reached its final density at ~890 °C. Above this value, grain growth became important and induced an intra-granular porosity, which was responsible for density decrease. At ~1180 °C, a liquid phase was formed due to formation of a binary eutectic between FA and fluorite contained in the powder as impurity. This liquid phase further promoted the coarsening process and induced formation of large pores at high temperatures [189].
In general, sintering occurs only when the driving force is sufficiently high, while the latter relates to the decrease in surface and interfacial energies of the system by matter (molecules, atoms, or ions) transport, which can proceed by solid, liquid, or gaseous phase diffusion. Namely, when solids are heated to high temperatures, their constituents are driven to move to fill up pores and open channels between the grains of powders, as well as to compensate for the surface energy differences among their convex and concave surfaces (matter moves from convex to concave). At the initial stages, bottlenecks are formed and grow among the particles. Existing vacancies tend to flow away from the surfaces of sharply curved necks; this is an equivalent of a material flow towards the necks, which grow as the voids shrink. Small contact areas among the particles expand and, at the same time, a density of the compact increases and the total void volume decreases. As the pores and open channels are closed during a heat treatment, the particles become tightly bonded together, and density, strength, and fatigue resistance of the sintered object improve greatly. Grain boundary diffusion was identified as the dominant mechanism for densification [190]. Furthermore, strong chemical bonds are formed among the particles, and loosely compacted green bodies are hardened to denser materials [107][108][109]. Further knowledge on the ceramic sintering process can be found elsewhere [191].
In the case of CaPO4, the earliest research on their sintering was published in 1971 [192]. Since then, numerous research on this subject have been published, and several specific processes have been found to occur during CaPO4 sintering. Firstly, moisture, carbonates and all other volatile chemicals remaining from the synthesis stage, such as ammonia, nitrates, and any organic compounds, are removed as gaseous products. Secondly, unless powders are sintered, the removal of these gases facilitates production of denser ceramics with subsequent shrinkage of the samples. Thirdly, all chemical changes are accompanied by a concurrent increase in crystal size and a decrease in the specific surface area. Fourthly, a chemical decomposition of all acidic orthophosphates and their transformation into other phosphates (e.g., 2HPO42− → P2O74− + H2O) takes place. In addition, sintering causes toughening [18], densification [19][193], partial dehydroxylation (in the case of HA) [19], a partial evaporation and condensation of phosphates [194], and grain growth [190][195], as well as a mechanical strength increasing [196][197][198]. The latter events are due to presence of air and other gases filling gaps among the particles of unsintered powders. At sintering, the gases move towards the outside of powders, and green bodies shrink owing to decrease of distances among the particles. For example, sintering of biologically formed apatites was investigated [199][200] and the obtained products were characterized [201][202]. In all cases, the numerical value of the Ca/P ratio in sintered apatites of biological origin was higher than that of the stoichiometric HA. One should mention that in the vast majority of cases, CaPO4 with Ca/P ratio < 1.5 are not sintered, since these compounds are thermally unstable, while sintering of nonstoichiometric CaPO4 (CDHA and ACP) always leads to their transformation into various types of biphasic, triphasic, and multiphase formulations [20].
An extensive study on the effects of sintering temperature and time on the properties of HA bioceramics revealed a correlation between these parameters and density, porosity, grain size, chemical composition, and strength of the scaffolds [203]. Namely, sintering below ~1000 °C was found to result in initial particle coalescence, with little or no densification and a significant loss of the surface area and porosity. The degree of densification appeared to depend on the sintering temperature, whereas the degree of ionic diffusion was governed by the period of sintering [203]. To enhance sinterability of CaPO4, a variety of sintering additives might be added [204][205][206][207].
Solid-state pressureless sintering is the simplest procedure. For example, HA bioceramics can be pressurelessly sintered up to the theoretical density at 1000–1200 °C. Processing at even higher temperatures usually lead to exaggerated grain growth and decomposition because HA becomes unstable at temperatures exceeding ~1300 °C [45][46][47][48][49][50][208][209][210]. The decomposition temperature of HA bioceramics is a function of the partial pressure of water vapor. Moreover, processing under vacuum leads to an earlier decomposition of HA, while processing under high partial pressure of water prevents the decomposition. On the other hand, the presence of water in the sintering atmosphere was reported to inhibit densification of HA and accelerate grain growth [211]. Unexpectedly, an application of a magnetic field during sintering was found to influence the growth of HA grains [195]. A definite correlation between hardness, density, and a grain size in sintered HA bioceramics was found; despite exhibiting high bulk density, hardness started to decrease at a certain critical grain size limit [212][213][214].
Since grain growth occurs mainly during the final stage of sintering, to avoid this, a new method called ‘‘two-step sintering’’ (TSS) was proposed [215]. The method consists of suppressing grain boundary migration responsible for grain growth, while keeping grain boundary diffusion that promotes densification. The TSS approach was successfully applied to CaPO4 bioceramics [27][171][216][217][218][219]. For example, HA compacts prepared from nanodimensional powders were two-step sintered. The average grain size of near full dense (>98%) HA bioceramics made via conventional sintering was found to be ~1.7 μm, while that for TSS HA bioceramics was ~190 nm (i.e., ~9 times less) with simultaneous increasing of the fracture toughness of samples from 0.98 ± 0.12 to 1.92 ± 0.20 MPa m1/2. In addition, due to the lower second-step sintering temperature, no HA phase decomposition was detected in the TSS method [216].
Hot pressing, hot isostatic pressing [28][112][117][118], or hot pressing with post-sintering [220][221], as well as “cold sintering” (which is very similar to hot pressing) [222] processes make it possible to decrease the temperature of the densification process, diminish the grain size, and achieve higher densities. This leads to finer microstructures, higher thermal stability, and subsequently better mechanical properties of CaPO4 bioceramics. In addition, microwave [223][224][225][226][227][228], spark plasma, flash [229][230], and ultrafast high-temperature [231] sintering techniques are alternative methods to the conventional sintering, hot pressing, and hot isostatic pressing. Both alternative methods were found to be time- and energy-efficient densification techniques. Further developments are still possible. For example, a hydrothermal hot pressing method was developed to fabricate OCP [232], CDHA [233], HA/β-TCP [234], and HA [220][235][236][237][238] bioceramics with neither thermal dehydration nor thermal decomposition. Further details on the sintering and firing processes of CaPO4 bioceramics are available in the literature [48][239][240].
To conclude this, one should note that the sintering stage is not always necessary. For example, CaPO4-based bulk bioceramics with the reasonable mechanical properties might be prepared by means of self-setting (self-hardening) formulations (see Section 6.1. Self-setting (Self-hardening) Formulations below). Furthermore, the reader’s attention is directed to an excellent research on various ceramic manufacturing techniques [241], in which various ceramic processing techniques are well described.

2. The Major Properties

2.1. Mechanical Properties

The modern generation of biomedical materials should stimulate the body’s own self-repairing abilities [242]. Therefore, during healing, a mature bone should replace the modern grafts and this process must occur without transient loss of the mechanical support. Unluckily for material scientists, a human body provides one of the most inhospitable environments for the implanted biomaterials. It is warm, wet, and both chemically and biologically active. For example, a diversity of body fluids in various tissues might have a solution pH varying from 1 to 9. In addition, a body is capable of generating quite massive force concentrations, and the variance in such characteristics among individuals might be enormous. Typically, bones are subjected to ~4 MPa loads, whereas tendons and ligaments experience peak stresses in the range of 40–80 MPa. The hip joints are subjected to an average load of up to three times the body weight (3000 N), and peak loads experienced during jumping can be as high as 10 times the body weight. These stresses are repetitive and fluctuating depending on the nature of the activities, which can include standing, sitting, jogging, stretching, and climbing. Therefore, all types of implants must sustain attacks of a great variety of aggressive conditions [243]. Regrettably, there is presently no artificial material fulfilling all these requirements.
Now it is important to mention that the mechanical behavior of any ceramics is rather specific; namely, ceramics is brittle, which is attributed to high-strength ionic bonds. Thus, it is not possible for plastic deformation to happen prior to failure, as a slip cannot occur. Therefore, ceramics fail in a dramatic manner. Namely, if a crack is initiated, its progress will not be hindered by the deformation of material ahead of the crack, as would be the case in a ductile material (e.g., a metal). In ceramics, the crack will continue to propagate, rapidly resulting in a catastrophic breakdown. In addition, the mechanical data typically have a considerable amount of scatter [108]. Alas, all of these are applicable to CaPO4 bioceramics.
For dense bioceramics, the strength is a function of the grain sizes. Namely, finer-grain-size bioceramics have smaller flaws at the grain boundaries and thus are stronger than ones with larger grain sizes. Thus, in general, the strength for ceramics is proportional to the inverse square root of the grain sizes [244]. In addition, the mechanical properties decrease significantly with increasing content of an amorphous phase, microporosity, and grain sizes, while a high crystallinity, a low porosity, and small grain sizes tend to give a higher stiffness, a higher compressive and tensile strength, and a greater fracture toughness. Furthermore, ceramics strength appears to be very sensitive to slow crack growth [245]. Accordingly, from the mechanical point of view, CaPO4 bioceramics appear to be brittle polycrystalline materials for which the mechanical properties are governed by crystallinity, grain size, grain boundaries, porosity, and composition [246]. Thus, it possesses poor mechanical properties (for instance, a low impact and fracture resistances) that do not allow CaPO4 bioceramics to be used in load-bearing areas, such as artificial teeth or bones [247][248][249][250]. For example, fracture toughness (this is a property that describes the ability of a material containing a crack to resist fracture and is one of the most important properties of any material for virtually all design applications) of HA bioceramics does not exceed the value of ~1.2 MPa·m1/2 [251] (human bone: 2–12 MPa·m1/2). It decreases exponentially with increasing porosity [252]. Generally, fracture toughness increases with grain size decreasing. However, in some materials, especially noncubic ceramics, fracture toughness reaches the maximum and rapidly drops with decreasing grain size. For example, a fracture toughness of pure hot-pressed HA with grain sizes between 0.2–1.2 µm was investigated. The researchers found two distinct trends, where fracture toughness decreased with increasing grain size above ~0.4 µm and subsequently decreased with decreasing grain size. The maximum fracture toughness measured was 1.20 ± 0.05 MPa·m1/2 at ~0.4 µm [253]. Fracture energy of HA bioceramics is in the range of 2.3–20 J/m2, while the Weibull modulus (a measure of the spread or scatter in fracture strength) is low (~5–12) in wet environments, which means that HA behaves as a typical brittle ceramics and indicates a low reliability of HA implants [254]. Porosity has a great influence on the Weibull modulus [255][256]. In addition, the reliability of HA bioceramics was found to depend on deformation mode (bending or compression), along with pore size and pore size distribution: reliability was higher for smaller average pore sizes in bending but lower for smaller pore sizes in compression [257]. Interestingly, three peaks of internal friction were found at temperatures of about –40, 80, and 130 °C for HA but no internal friction peaks were obtained for FA in the measured temperature range; this effect was attributed to the differences of F and OH positions in FA and HA, respectively [258]. Differences in internal friction values were also found between HA and TCP [259].
Bending, compressive, and tensile strengths of dense HA bioceramics are in the ranges of 38–250, 120–900, and 38–300 MPa, respectively. Similar values for porous HA bioceramics are substantially lower: 2–11, 2–100, and ~3 MPa, respectively [254]. These wide variations in the properties are due to both structural variations (e.g., an influence of remaining microporosity, grain sizes, presence of impurities, etc.) and manufacturing processes, and they are also caused by a statistical nature of the strength distribution. Strength was found to increase with Ca/P ratio increasing, reaching the maximum value around Ca/P ~1.67 (stoichiometric HA) and decreasing suddenly when Ca/P > 1.67 [254]. Furthermore, strength decreases almost exponentially with increasing porosity [260][261]. However, by changing the pore geometry, it is possible to influence the strength of porous bioceramics. It is also worth mentioning that porous CaPO4 bioceramics are considerably less fatigue-resistant than dense ones (in materials science, fatigue is the progressive and localized structural damage that occurs when a material is subjected to cyclic loading). Both grain sizes and porosity are reported to influence the fracture path, which itself has little effect on the fracture toughness of CaPO4 bioceramics [246][262]. However, no obvious decrease in mechanical properties was found after CaPO4 bioceramics had been aged in the various solutions during the different periods of time [263].
Young’s (or elastic) modulus of dense HA bioceramics is in the range of 3–120 GPa [264][265], which is more or less similar to those of the most resistant components of the natural calcified tissues (dental enamel: ~74 GPa, dentine: ~21 GPa, compact bone: ~18–22 GPa). This value depends on porosity [266][267]. Nevertheless, dense bulk compacts of HA have mechanical resistances of the order of 100 MPa versus ~00 MPa of human bones, drastically diminishing their resistances in the case of porous bulk compacts [268]. Young’s modulus measured in bending is between 44 and 88 GPa. To investigate the subject in more detail, various types of modeling and calculations are increasingly used [269][270][271][272][273]. For example, the elastic properties of HA appeared to be significantly affected by the presence of vacancies, which softened HA via reducing its elastic modules [273]. In addition, a considerable anisotropy in the stress–strain behavior of the perfect HA crystals was found by ab initio calculations [270]. The crystals appeared to be brittle for tension along the z-axis with the maximum stress of ~9.6 GPa at 10% strain. Furthermore, the structural analysis of the HA crystal under various stages of tensile strain revealed that the deformation behavior manifested itself mainly in the rotation of PO4 tetrahedrons with concomitant movements of both the columnar and axial Ca ions [270]. Data for single crystals are also available [274]. Vickers hardness (a measure of the resistance to permanent indentation) of dense HA bioceramics is within 3–7 GPa, while the Poisson’s ratio (the ratio of the contraction or transverse strain to the extension or axial strain) for HA is about 0.27, which is close to that of bones (~0.3). At temperatures within 1000–1100 °C, dense HA bioceramics were found to exhibit superplasticity with a deformation mechanism based on grain boundary sliding [275][276][277]. Furthermore, both wear resistance and friction coefficient of dense HA bioceramics are comparable to those of dental enamel [254].
Due to a high brittleness (associated with a low crack resistance), the biomedical applications of CaPO4 bioceramics are focused on production of non-load-bearing implants, such as pieces for middle ear surgery, filling of bone defects in oral or orthopedic surgery, and coating of dental implants and metallic prosthesis (see below) [14][278][279]. Therefore, methods are continuously sought to improve the reliability of CaPO4 bioceramics. Namely, the mechanical properties of sintered bioceramics might be improved by changing the morphology of the initial CaPO4 [280]. In addition, diverse reinforcements (ceramics, metals, or polymers) have been applied to manufacture various biocomposites and hybrid biomaterials [281], but that is another story. However, successful hybrid formulations consisting of CaPO4 only [282][283][284][285][286][287][288][289] are within the scope. Namely, bulk HA bioceramics might be reinforced by HA whiskers [283][284][285][286][287]. Furthermore, various biphasic apatite/TCP formulations were tested [282][288][289] and, for example, a superior superplasticity of HA/β-TCP biocomposites to HA bioceramics was detected [288].
Another method to improve the mechanical properties of CaPO4 bioceramics is to cover the items by polymeric coatings [290][291][292] or infiltrate porous structures by polymers [293][294][295]; however, this is another topic. Other approaches are also possible [86]. Further details on the mechanical properties of CaPO4 bioceramics are available elsewhere [252][254][296], where interested readers are referred.

2.2. Electric/Dielectric and Piezoelectric Properties

Recently, an interest in both electric/dielectric [223][297][298][299][300][301][302][303][304][305][306][307][308][309] and piezoelectric [310][311] properties of CaPO4 bioceramics has been expressed. In addition, some types of CaPO4 bioceramics (namely, HA) appear to be electrets [312][313]. An electret is a dielectric material that has a quasi-permanent electric charge or dipole polarization. An electret generates internal and external electric fields, and is the electrostatic equivalent of a permanent magnet [314]. For example, a surface ionic conductivity of both porous and dense HA bioceramics was examined for humidity sensor applications, since the room temperature conductivity was influenced by relative humidity [298]. Namely, the ionic conductivity of HA is a subject of research for its possible use as a gas sensor for alcohol [299], carbon dioxide [297][306], or carbon monoxide [302]. Electric measurements were also used as a characterization tool to study the evolution of microstructure in HA bioceramics [300]. More to the point, the dielectric properties of HA were examined to understand its decomposition to β-TCP [299]. In the case of CDHA, the electric properties, in terms of ionic conductivity, were found to increase after compression of the samples at 15 t/cm2, which was attributed to establishment of some order within the apatitic network [301]. The conductivity mechanism of CDHA appeared to be multiple [304]. Furthermore, there are attempts to develop HA and/or CDHA electrets for biomedical utilization [303][312][313].
The electric properties of CaPO4 bioceramics appear to influence their biomedical applications. For example, there is an interest in polarization of HA bioceramics to generate a surface charge by the applying a constant DC electric field of 0.5–10.0 kV/cm at elevated temperatures (300–1000 °C) to samples previously sintered at ~ 1000–1250 °C for ~2 h. This technique is called thermally stimulated polarization and its results indicated that the polarization effects were a consequence of electrical dipoles associated with the formation of defects inside crystal grains, such as thermally-induced OH vacancies, and of the space charge polarization that originated in the grain boundaries [315][316][317]. The presence of surface charges on HA was shown to have a significant effect on both in vitro and in vivo crystallization of biological apatite [318][319][320][321][322][323][324], as well as on an ability to adsorb various types of phosphate ions [317]. Furthermore, a growth of both biomimetic CaPO4 and bones was found to be accelerated on negatively charged surfaces and decelerated at positively charged surfaces [322][323][324][325][326][327][328][329][330][331]. A similar effect was found for adsorption of bovine serum albumin [332]. In addition, the electric polarization of CaPO4 was found to accelerate a cytoskeleton reorganization of osteoblast-like cells [333][334][335][336], extend bioactivity [337], enhance bone ingrowth through the pores of porous implants [338], and influence the cell activity [339][340]. The positive effect of electric polarization was found for carbonated apatite as well [341]. There is an interesting study on the interaction of a blood coagulation factor on electrically polarized HA surfaces [342]. Further details on the electric properties of CaPO4-based bioceramics are available in the literature [223][307][308][313].

2.3. Possible Transparency

Single crystals of all types of CaPO4 are optically transparent for the visible light. As bioceramics of CaPO4 have a polycrystalline nature with a random orientation of big amounts of small crystals, it is opaque and of white color, unless colored dopants have been added. However, in some cases, a transparency is convenient to provide some essential advantages (e.g., to enable direct viewing of living cells, their attachment, spreading, proliferation, and osteogenic differentiation cascade in a transmitted light). Thus, transparent CaPO4 bioceramics [343] have been prepared and investigated [28][112][114][275][343][344][345][346][347][348][349][350][351][352][353][354][355][356][357]. They can exhibit an optical transmittance of ~66% at a wavelength of 645 nm [355]. The preparation techniques include a hot isostatic pressing [28][112][114][356], an ambient-pressure sintering [350], a gel casting coupled with a low-temperature sintering [351][354], and a pulse electric current sintering [352], as well as spark plasma [275][344][345][346][347][348][349][358][359][360] and flash [229][230] sintering techniques. Fully dense, transparent CaPO4 bioceramics are obtained at temperatures above ~800 °C. Depending on the preparation technique, the transparent bioceramics have a uniform grain size ranging from ~67 nm [28] to ~250 μm [351] and are always pore-free. Furthermore, translucent CaPO4 bioceramics are also known [28][192][361][362][363]. Concerning possible biomedical applications, the optically transparent in visible light CaPO4 bioceramics can be useful for direct viewing of other objects, such as cells, in some specific experiments [353]. In addition, the transparency for laser light CaPO4 bioceramics may appear to be convenient for minimal invasive surgery by allowing passing the laser beam through it to treat the injured tissues located underneath. However, due to a lack of both porosity and the necessity to have see-through implants inside the body, the transparent and translucent forms of CaPO4 bioceramics will hardly be extensively used in medicine, except for the aforementioned cases and possible eye implants.

2.4. Porosity

Porosity is defined as a percentage of voids in solids, and this morphological property is independent of the material. The surface area of porous bodies is much higher, which guarantees a good mechanical fixation in addition to providing sites on the surface that allow chemical bonding between the bioceramics and bones [364]. Furthermore, a porous material may have both closed (isolated) pores and open (interconnected) pores. The latter look similar to tunnels and are accessible by gases, liquids, and particulate suspensions [365]. The open-cell nature of porous materials (also known as reticulated materials) is a unique characteristic essential in many applications. In addition, pore dimensions are also important. Namely, the dimensions of open pores are directly related to bone formation, since such pores grant both the surface and space for cell adhesion and bone ingrowth [366][367][368]. On the other hand, pore interconnection provides the ways for cell distribution and migration, and it allows an efficient in vivo blood vessel formation suitable for sustaining bone tissue neo-formation and possibly remodeling [54][338][369][370][371][372][373]. Namely, porous CaPO4 bioceramics are colonized easily by cells and bone tissues [369][372][374][375][376][377][378][379]. Therefore, interconnecting macroporosity (pore size > 100 μm) [25][364][369][380][381] is intentionally introduced in solid bioceramics. Calcining of natural bones and teeth appears to be the simplest way to prepare porous CaPO4 bioceramics [4][5][6][7][8][9][10][11]. In addition, macroporosity might be formed artificially due to a release of various easily removable compounds and, for that reason, incorporation of pore-creating additives (porogens) is the most popular technique to create macroporosity. The porogens are crystals, particles, or fibers of either volatile (they evolve gases at elevated temperatures) or soluble substances. The popular examples comprise paraffin [382][383][384], naphthalene [246][385][386][387], sucrose [388][389], NaHCO3 [390][391][392], NaCl [393][394], polymethylmethacrylate [395][396][397][398], hydrogen peroxide [399][400][401][402], cellulose [403], and its derivatives [16]. Several other compounds [261][404][405][406][407][408][409][410][411], including carbon nanotubes [412], might be used as porogens as well. The ideal porogen should be nontoxic and be removed at ambient temperature, thereby allowing the bioceramic/porogen mixture to be injected directly into a defect site and allowing the scaffold to fit the defect [413].
Many other techniques, such as replication of polymer foams by impregnation [147][148][149][152][414][415][416][417][418], various types of casting [130][131][135][137][402][419][420][421][422][423][424][425][426][427], suspension foaming [42], surfactant washing [428], microemulsions [429][430], and ice templating [431][432][433][434], as well as many other approaches [71][127][395][435][436][437][438][439][440][441][442][443][444][445][446][447][448][449][450][451][452][453][454][455][456][457][458][459][460][461][462], have been applied to fabricate porous CaPO4 bioceramics. Some of them are summarized [413]. In addition, both natural CaCO3 porous materials, such as coral skeletons [463][464], shells [464][465], and even wood [466], as well as artificially prepared ones [467], can be converted into porous CaPO4 under the hydrothermal conditions (250 °C, 24–48 h) with the microstructure undamaged. Porous HA bioceramics can also be obtained by hydrothermal hot pressing. This technique allows solidification of the HA powder at 100–300 °C (30 MPa, 2 h) [238]. In another approach, bi-continuous water-filled microemulsions are used as preorganized systems for the fabrication of needle-like frameworks of crystalline HA (2 °C, 3 weeks) [429][430]. In addition, porous CaPO4 might be prepared by a combination of gel casting and foam burn out methods [172][174], as well as by hardening of the self-setting formulations [383][384][391][392][393][394][454]. Lithography was used to print a polymeric material, followed by packing with HA and sintering [441]. Hot pressing was applied as well [468][469]. More to the point, an HA suspension can be cast into a porous CaCO3 skeleton, which is then dissolved, leaving a porous network [437]. A 3D periodic macroporous frame of HA was fabricated via a template-assisted colloidal processing technique [443][446]. In addition, porous HA bioceramics might be prepared by using different starting HA powders and sintering at various temperatures by a pressureless sintering [439]. Porous bioceramics with an improved strength might be fabricated from CaPO4 fibers or whiskers. In general, fibrous porous materials are known to exhibit an improved strength due to fiber interlocking, crack deflection, and/or pullout [470]. Namely, porous bioceramics with well-controlled open pores were processed by sintering of fibrous HA particles [438]. In another approach, porosity was achieved by firing apatite-fiber compacts mixed with carbon beads and agar. By varying the compaction pressure, firing temperature and carbon/HA ratio, the total porosity was controlled in the ranges from ~40% to ~85% [16]. Finally, a superporous (~85% porosity) HA bioceramic was developed as well [449][451][452]. Additional information on the processing routes to produce porous ceramics can be found in the literature [471].
Bioceramic microporosity (pore size < 10 μm), which is defined by its capacity to be impregnated by biological fluids [472], results from the sintering process, while the pore dimensions mainly depend on the material composition, thermal cycle, and sintering time. The microporosity provides both a greater surface area for protein adsorption and increased ionic solubility. For example, embedded osteocytes distributed throughout microporous rods might form a mechanosensory network, which would not be possible in scaffolds without microporosity [473][474]. CaPO4 bioceramics with nanodimensional (<100 nm) pores might be fabricated as well [475][476][477][478][479]. It is important to stress that differences in porogens usually influence the bioceramics’ macroporosity, while differences in sintering temperatures and conditions affect the percentage of microporosity. Usually, the higher the sintering temperature, the lower both the microporosity content and the specific surface area of bioceramics. Namely, HA bioceramics sintered at ~1200 °C show significantly less microporosity and a dramatic change in crystal sizes, if compared with those sintered at ~1050 °C [480]. Furthermore, the average shape of pores was found to transform from strongly oblate to round at higher sintering temperatures [481]. The total porosity (macroporosity + microporosity) of CaPO4 bioceramics was reported to be ~70% [482] or even ~85% [449][451][452] of the entire volume. In the case of coralline HA or bovine-derived apatites, the porosity of the original biologic material (coral or bovine bone) is usually preserved during processing [483]. To finalize the production topic, creation of the desired porosity in CaPO4 bioceramics is a rather complicated engineering task and interested readers are referred to the additional publications on the subject [261][368][453][484][485][486][487][488][489].
Regarding the biomedical importance of porosity, studies revealed that increasing of both the specific surface area and pore volume of bioceramics might greatly accelerate the in vivo process of apatite deposition and, therefore, enhance the bone-forming bioactivity. More importantly, a precise control over the porosity, pore dimensions, and internal pore architecture of bioceramics on different length scales is essential for understanding the structure–bioactivity relationship and the rational design of better bone-forming biomaterials [487][490][491]. Namely, in antibiotic charging experiments, CaPO4 bioceramics with nanodimensional (<100 nm) pores showed a much higher charging capacity (1621 μg/g) than those of commercially available CaPO4 (100 μg/g), which did not contain nanodimensional porosity [485]. In other experiments, porous blocks of HA were found to be viable carriers with sustained release profiles for drugs [492] and antibiotics over 12 days [493] and 12 weeks [494], respectively. Unfortunately, porosity significantly decreases the strength of implants [257][262][296]. Thus, porous CaPO4 implants cannot be loaded and are used to fill only small bone defects; however, their strength increases gradually when bones ingrow into the porous network of CaPO4 implants [52][495][496][497][498]. For example, bending strengths of 4–60 MPa for porous HA implants filled with 50%–60% of cortical bone were reported [495], while in another study an ingrown bone increased strength of porous HA bioceramics by a factor of three to four [497].
Unfortunately, the biomedical effects of bioceramics’ porosity are not straightforward. For example, the in vivo response of CaPO4 to different porosity was investigated, and a hardly any effect of macropore dimensions (~150, ~260, ~510, and ~1220 μm) was observed [499]. In another study, a greater differentiation of mesenchymal stem cells was observed when cultured on ~200 μm pore size HA scaffolds when compared to those on ~500 μm pore size HA [500]. The latter finding was attributed to the fact that a higher pore volume in ~500 μm macropore scaffolds might contribute to a lack of cell confluency, leading to the cells proliferating before beginning differentiation. In addition, the researchers hypothesized that bioceramics having less than the optimal pore dimensions induced quiescence in differentiated osteoblasts due to reduced cell confluency [500]. In still another study, the use of BCP (HA/TCP = 65/35 wt.%) scaffolds with cubic pores of ~500 μm resulted in the highest bone formation compared with the scaffolds with lower (~100 μm) or higher (~1000 μm) pore sizes [501]. Furthermore, CaPO4 bioceramics with greater strut porosity appeared to be more osteoinductive [502]. As early as 1979, Holmes suggested that the optimal pore range was 200–400 μm with the average human osteon size of ~223 μm [503]. In 1997, Tsurga and coworkers implied that the optimal pore size of bioceramics that supported ectopic bone formation was 300–400 μm [504]. Thus, there is no need to create CaPO4 bioceramics with very big pores; however, the pores must be interconnected [370][380][381][505]. Interconnectivity governs a depth of cells or tissue penetration into the porous bioceramics, and it allows development of blood vessels required for new bone nourishing and wastes removal [506][507]. Nevertheless, the total porosity of implanted bioceramics appears to be important. For example, 60% porous β-TCP granules achieved a higher bone fusion rate than 75% porous β-TCP granules in lumbar posterolateral fusion [473].
More details on the importance of CaPO4 bioceramics porosity on bone regeneration are available in a topical research [508].

3. Biomedical Applications

Since Levitt et al. described a method of preparing FA bioceramics and suggested their possible use in medical applications in 1969 [509], CaPO4 bioceramics have been widely tested for clinical applications. Namely, over 400 forms, compositions, and trademarks are currently either in use or under consideration in many areas of orthopedics and dentistry [510], with even more in development. In addition, various formulations containing demineralized bone matrix (commonly abbreviated as DBM) are produced for bone grafting. For example, bulk materials, available in dense and porous forms, are used for alveolar ridge augmentation, immediate tooth replacement, and maxillofacial reconstruction [511][512]. Other examples comprise burr-hole buttons [513][514], cosmetic (nonfunctional) eye replacements such as Bio-Eye® [515][516][517][518][519][520], increment of the hearing ossicles [521][522][523], and spine fusion [524][525][526][527], as well as repair of bone [51][528][529], craniofacial [530], and dental [531] defects. In order to permit growth of new bone into defects, a suitable bioresorbable material should fill these defects. Otherwise, ingrowth of fibrous tissue might prevent bone formation within the defects.
In spite of the aforementioned serious mechanical limitations (see Section 4.1. Mechanical Properties), bioceramics of CaPO4 are available in various physical forms: powders, particles, granules (or granulates), dense blocks, porous scaffolds, self-setting formulations, implant coatings, and composite components of different origin (natural, biological, or synthetic), often with specific shapes, such as implants, prostheses, or prosthetic devices. In addition, CaPO4 are also applied as nonhardening injectable formulations [532][533][534][535][536][537] and pastes [537][538][539][540][541]. Generally, they consist of a mixture of CaPO4 powders or granules and a “glue”, which can be a highly viscous hydrogel. More to the point, custom-designed shapes such as wedges for tibial opening osteotomy, cones for spine and knee, and inserts for vertebral cage fusion are also available [482].
One should note that among the existing CaPO4, only certain compounds are useful for biomedical applications, because those having a Ca/P ionic ratio less than 1 are not suitable for implantation due to their high solubility and acidity. Furthermore, due to its basicity, TTCP alone cannot be suitable either. Nevertheless, researchers try [72]. In addition, to simplify biomedical applications, these “of little use” CaPO4 can be successfully combined with either other types of CaPO4 or other chemicals.

3.1. Self-Setting (Self-Hardening) Formulations

The need for bioceramics for minimal invasive surgery has induced the concept of self-setting (or self-hardening) formulations consisting of CaPO4 only to be applied as injectable and/or moldable bone substitutes [43][44][55][441][542]. After hardening, they form bulk CaPO4 bioceramics. In addition, there are reinforced formulations that, in a certain sense, might be defined as CaPO4 concretes [43]. Furthermore, self-setting formulations able to produce porous bulk CaPO4 bioceramics are also available [383][384][391][392][393][394][441][454][542][543][544][545].
All types of the self-setting CaPO4 formulations belong to low-temperature bioceramics. They are divided into two major groups. The first one is a dry mixture of two different types of CaPO4 (a basic one and an acidic one), in which, after being wetted, the setting reaction occurs according to an acid–base reaction. The second group contains only one CaPO4, such as ACP with Ca/P molar ratio within 1.50–1.67 or α-TCP: both of them form CDHA upon contact with an aqueous solution [43][55]. Chemically, setting (= hardening, curing) is due to the succession of dissolution and precipitation reactions. Mechanically, it results from crystal entanglement and intergrowth [546]. By influencing dimensions of forming CaPO4 crystals, it is possible to influence the mechanical properties of the hardened bulk bioceramics [547]. Sometimes, the self-set formulations are sintered to prepare high-temperature CaPO4 bioceramics [548]. Despite a large number of initial compositions, all types of self-setting CaPO4 formulations can form three products only: CDHA, DCPD, and, rarely, DCPA [43][44][55][441][542]. Special research on the topic are available in [43][44][548], where interested readers are referred for further details.

3.2. CaPO4 Deposits (Coatings, Films, and Layers)

For many years, the clinical application of CaPO4-based bioceramics has been largely limited to non-load-bearing parts of the skeleton due to their inferior mechanical properties. Therefore, materials with better mechanical properties appear to be necessary. For example, metallic implants are encountered in endoprostheses (total hip joint replacements) and artificial teeth sockets. As metals do not undergo bone bonding, i.e., they do not form a mechanically stable link between the implant and bone tissue, methods have been sought to improve contacts at the interface. One major method is to coat metals with CaPO4, which enables bonding ability between the metal and the bone [107][117][321][549][550][551].
A number of factors influence the properties of CaPO4 deposits (coatings, films, and layers). They include thickness (this will influence coating adhesion and fixation—the agreed optimum now seems to be within 50–100 µm), crystallinity (this affects the dissolution and biological behavior), phase and chemical purity, porosity, and adhesion. The coated implants combine the surface biocompatibility and bioactivity of CaPO4 with the core strength of strong substrates. Moreover, CaPO4 deposits decrease a release of potentially hazardous chemicals from the core implant and shield the substrate surface from environmental attack. In the case of porous implants, the CaPO4-coated surface enhances bone ingrowth into the pores [254]. The clinical results for CaPO4-deposited implants reveal that they have much longer lifetimes after implantation than uncoated devices and they are found to be particularly beneficial for younger patients. Further details on this topic are available in the special research [549][550][551].

3.3. Functionally Graded Bioceramics

In general, functionally gradient materials (FGMs) are defined as materials having either compositional or structural gradient from their surface to the interior. The idea of FGMs allows one device to possess two different properties. One of the most important combinations for the biomedical field is that of mechanical strength and biocompatibility. Namely, only surface properties govern a biocompatibility of the entire device. In contrast, the strongest material determines the mechanical strength of the entire device. Although this subject belongs to the previous section on coatings, films, and layers, in a certain sense, all types of implants covered by CaPO4 might be also considered as FGMs.
Within the scope, functionally graded bioceramics consisting of CaPO4 are considered and discussed only. Such formulations have been developed [395][423][426][486][552][553][554][555][556][557][558][559][560][561][562]. For example, dense sintered bodies with gradual compositional changes from α-TCP to HA were prepared by sintering diamond-coated HA compacts at 1280 °C under a reduced pressure, followed by heating under atmospheric conditions [552]. The content of α-TCP gradually decreased, while the content of HA increased with increasing depth from the surface. This functionally gradient bioceramic consisting of HA core and α-TCP surface showed potential value as a bone-substituting biomaterial [552]. Two types of functionally gradient FA/β-TCP biocomposites were prepared in another study [553].
In addition, it is well known that a bone cross-section from cancellous to cortical bone is nonuniform in porosity and pore dimensions. Thus, in various attempts to mimic the porous structure of bones, CaPO4 bioceramics with graded porosity have been fabricated [365][395][412][423][426][486][552][553][554][555]. For example, graded porous CaPO4 bioceramics can be produced by means of tape casting and lamination. Other manufacturing techniques, such as a compression molding process followed by impregnation and firing, are known as well [365]. In the first method, an HA slurry was mixed with a pore former. The mixed slurry was then cast into a tape. Using the same method, different tapes with different pore former sizes were prepared individually. The different tape layers were then laminated together. Firing was then performed to remove the pore formers and sinter the HA particle compacts, resulting in graded porous bioceramics [555]. This method was also used to prepare graded porous HA with a dense part (core or layer) in order to improve the mechanical strength, as dense ceramics are much stronger than porous ceramics. However, as in the pressure infiltration of mixed particles, this multiple tape casting also has the problem of poor connectivity of pores, although the pore size and the porosity are relatively easy to control. Furthermore, the lamination step also introduces additional discontinuity of the porosity on the interfaces between the stacked layers.
Since diverse biomedical applications require different configurations and shapes, the graded (or gradient) porous bioceramics can be grouped according to both the overall shape and the structural configuration [365]. The basic shapes include rectangular blocks and cylinders (or disks). For the cylindrical shape, there are configurations of dense core–porous layer, less porous core–more porous layer, dense layer–porous core, and less porous layer–more porous core. For the rectangular shape, in the gradient direction, i.e., the direction with varying porosity, pore size, or composition, there are configurations of porous top–dense bottom (same as porous bottom–dense top), porous top–dense center–porous bottom, dense top–porous center–dense bottom, etc. Concerning biomedical applications, a dense core–porous layer structure is suitable for implants of a high mechanical strength and with bone ingrowth for stabilization, whereas a less porous layer–more porous core configuration can be used for drug delivery systems. Furthermore, a porous top –dense bottom structure can be shaped into implants of articulate surfaces for wear resistance and with porous ends for bone ingrowth fixation, while a dense top–porous center–dense bottom arrangement mimics the structure of head skull. Further details on bioceramics with graded porosity can be found in the literature [365].

4. Non-Biomedical Applications of CaPO4

Due to their strong adsorption ability, surface acidity or basicity, and ion exchange abilities, some types of CaPO4 possess a catalytic activity [563][564][565][566][567][568][569][570][571][572][573][574][575]. As seen from the references, CaPO4 are able to catalyze oxidation and reduction reactions, as well as formation of C–C bonds. Namely, the application in oxidation reactions mainly includes oxidation of alcohol and dehydrogenation of hydrocarbons, while the reduction reactions include hydrogenolysis and hydrogenation. The formation of C–C bonds mainly comprises Claisen–Schmidt and Knoevenagel condensation reactions, Michael addition reaction, as well as Friedel–Crafts, Heck, Diels–Alder, and aldol reactions [570].
In addition, due to the chemical similarity to the inorganic part of mammalian calcified tissues, CaPO4 powders appear to be good solid carriers for chromatography of biological substances. Namely, high-value biological materials such as recombinant proteins, therapeutic antibodies, and nucleic acids are separated and purified [576][577][578][579][580][581][582]. Furthermore, some types of CaPO4 are used as a component of various sensors [297][298][302][303][306][583][584][585][586][587]. Finally, CaPO4 ceramics appear to be good adsorbents of fluorides [588]; however, since these subjects are almost irrelevant to bioceramics, they are not detailed further. Additional details and examples are available elsewhere [589].


  1. Dorozhkin, S.V. Calcium orthophosphates and human beings. A historical perspective from the 1770s until 1940. Biomatter 2012, 2, 53–70.
  2. Dorozhkin, S.V. A detailed history of calcium orthophosphates from 1770-s till 1950. Mater. Sci. Eng. C 2013, 33, 3085–3110.
  3. De Groot, K. (Ed.) Bioceramics of Calcium Phosphate; CRC Press; Taylor & Francis: Boca Raton, FL, USA, 1983; p. 146.
  4. Balazsi, C.; Weber, F.; Kover, Z.; Horvath, E.; Nemeth, C. Preparation of calcium-phosphate bioceramics from natural resources. J. Eur. Ceram. Soc. 2007, 27, 1601–1606.
  5. Gergely, G.; Wéber, F.; Lukács, I.; Illés, L.; Tóth, A.L.; Horváth, Z.E.; Mihály, J.; Balázsi, C. Nano-hydroxyapatite preparation from biogenic raw materials. Cent. Eur. J. Chem. 2010, 8, 375–381.
  6. Mondal, S.; Mahata, S.; Kundu, S.; Mondal, B. Processing of natural resourced hydroxyapatite ceramics from fish scale. Adv. Appl. Ceram. 2010, 109, 234–239.
  7. Lim, K.T.; Suh, J.D.; Kim, J.; Choung, P.H.; Chung, J.H. Calcium phosphate bioceramics fabricated from extracted human teeth for tooth tissue engineering. J. Biomed. Mater. Res. B Appl. Biomater. 2011, 99B, 399–411.
  8. Seo, D.S.; Hwang, K.H.; Yoon, S.Y.; Lee, J.K. Fabrication of hydroxyapatite bioceramics from the recycling of pig bone. J. Ceram. Proc. Res. 2012, 13, 586–589.
  9. Ho, W.F.; Hsu, H.C.; Hsu, S.K.; Hung, C.W.; Wu, S.C. Calcium phosphate bioceramics synthesized from eggshell powders through a solid state reaction. Ceram. Int. 2013, 39, 6467–6473.
  10. González-Rodríguez, L.; López-Álvarez, M.; Astray, S.; Solla, E.L.; Serra, J.; González, P. Hydroxyapatite scaffolds derived from deer antler: Structure dependence on processing temperature. Mater. Charact. 2019, 155, 109805.
  11. Arokiasamy, P.; Al Bakri Abdullah, M.M.; Abd Rahim, S.Z.; Luhar, S.; Sandu, A.V.; Jamil, N.H.; Nabiałek, M. Synthesis methods of hydroxyapatite from natural sources: A review. Ceram. Int. 2022, 48, 14959–14979.
  12. Grigoraviciute-Puroniene, I.; Zarkov, A.; Tsuru, K.; Ishikawa, K.; Kareiva, A. A novel synthetic approach for the calcium hydroxyapatite from the food products. J. Sol-Gel Sci. Technol. 2019, 91, 63–71.
  13. Tosun, G.U.; Sakhno, Y.; Jaisi, D.P. Synthesis of hydroxyapatite nanoparticles from phosphorus recovered from animal wastes. ACS Sustain. Chem. Eng. 2021, 9, 15117–15126.
  14. Vallet-Regí, M.; González-Calbet, J.M. Calcium phosphates as substitution of bone tissues. Progr. Solid State Chem. 2004, 32, 1–31.
  15. Layrolle, P.; Ito, A.; Tateishi, T. Sol-gel synthesis of amorphous calcium phosphate and sintering into microporous hydroxyapatite bioceramics. J. Am. Ceram. Soc. 1998, 81, 1421–1428.
  16. Engin, N.O.; Tas, A.C. Manufacture of macroporous calcium hydroxyapatite bioceramics. J. Eur. Ceram. Soc. 1999, 19, 2569–2572.
  17. Ahn, E.S.; Gleason, N.J.; Nakahira, A.; Ying, J.Y. Nanostructure processing of hydroxyapatite-based bioceramics. Nano Lett. 2001, 1, 149–153.
  18. Khalil, K.A.; Kim, S.W.; Dharmaraj, N.; Kim, K.W.; Kim, H.Y. Novel mechanism to improve toughness of the hydroxyapatite bioceramics using high-frequency induction heat sintering. J. Mater. Process. Technol. 2007, 187–188, 417–420.
  19. Laasri, S.; Taha, M.; Laghzizil, A.; Hlil, E.K.; Chevalier, J. The affect of densification and dehydroxylation on the mechanical properties of stoichiometric hydroxyapatite bioceramics. Mater. Res. Bull. 2010, 45, 1433–1437.
  20. Dorozhkin, S.V. Multiphasic calcium orthophosphate (CaPO4) bioceramics and their biomedical applications. Ceram. Int. 2016, 42, 6529–6554.
  21. LeGeros, R.Z.; Lin, S.; Rohanizadeh, R.; Mijares, D.; LeGeros, J.P. Biphasic calcium phosphate bioceramics: Preparation, properties and applications. J. Mater. Sci. Mater. Med. 2003, 14, 201–209.
  22. Daculsi, G.; Laboux, O.; Malard, O.; Weiss, P. Current state of the art of biphasic calcium phosphate bioceramics. J. Mater. Sci. Mater. Med. 2003, 14, 195–200.
  23. Dorozhkina, E.I.; Dorozhkin, S.V. Mechanism of the solid-state transformation of a calcium-deficient hydroxyapatite (CDHA) into biphasic calcium phosphate (BCP) at elevated temperatures. Chem. Mater. 2002, 14, 4267–4272.
  24. Daculsi, G. Biphasic calcium phosphate granules concept for injectable and mouldable bone substitute. Adv. Sci. Technol. 2006, 49, 9–13.
  25. Lecomte, A.; Gautier, H.; Bouler, J.M.; Gouyette, A.; Pegon, Y.; Daculsi, G.; Merle, C. Biphasic calcium phosphate: A comparative study of interconnected porosity in two ceramics. J. Biomed. Mater. Res. B Appl. Biomater. 2008, 84B, 1–6.
  26. Daculsi, G.; Baroth, S.; LeGeros, R.Z. 20 years of biphasic calcium phosphate bioceramics development and applications. Ceram. Eng. Sci. Proc. 2010, 30, 45–58.
  27. Lukić, M.; Stojanović, Z.; Škapin, S.D.; Maček-Kržmanc, M.; Mitrić, M.; Marković, S.; Uskoković, D. Dense fine-grained biphasic calcium phosphate (BCP) bioceramics designed by two-step sintering. J. Eur. Ceram. Soc. 2011, 31, 19–27.
  28. Descamps, M.; Boilet, L.; Moreau, G.; Tricoteaux, A.; Lu, J.; Leriche, A.; Lardot, V.; Cambier, F. Processing and properties of biphasic calcium phosphates bioceramics obtained by pressureless sintering and hot isostatic pressing. J. Eur. Ceram. Soc. 2013, 33, 1263–1270.
  29. Owen, R.G.; Dard, M.; Larjava, H. Hydoxyapatite/beta-tricalcium phosphate biphasic ceramics as regenerative material for the repair of complex bone defects. J. Biomed. Mater. Res. B Appl. Biomater. 2018, 106B, 2493–2512.
  30. Li, Y.; Kong, F.; Weng, W. Preparation and characterization of novel biphasic calcium phosphate powders (α-TCP/HA) derived from carbonated amorphous calcium phosphates. J. Biomed. Mater. Res. B Appl. Biomater. 2009, 89B, 508–517.
  31. Sureshbabu, S.; Komath, M.; Varma, H.K. In situ formation of hydroxyapatite –alpha tricalcium phosphate biphasic ceramics with higher strength and bioactivity. J. Am. Ceram. Soc. 2012, 95, 915–924.
  32. Radovanović, Ž.; Jokić, B.; Veljović, D.; Dimitrijević, S.; Kojić, V.; Petrović, R.; Janaćković, D. Antimicrobial activity and biocompatibility of Ag+- and Cu2+-doped biphasic hydroxyapatite/α-tricalcium phosphate obtained from hydrothermally synthesized Ag+- and Cu2+-doped hydroxyapatite. Appl. Surf. Sci. 2014, 307, 513–519.
  33. Oishi, M.; Ohtsuki, C.; Kitamura, M.; Kamitakahara, M.; Ogata, S.; Miyazaki, T.; Tanihara, M. Fabrication and chemical durability of porous bodies consisting of biphasic tricalcium phosphates. Phosphorus Res. Bull. 2004, 17, 95–100.
  34. Kamitakahara, M.; Ohtsuki, C.; Oishi, M.; Ogata, S.; Miyazaki, T.; Tanihara, M. Preparation of porous biphasic tricalcium phosphate and its in vivo behavior. Key Eng. Mater. 2005, 59, 281–284.
  35. Wang, R.; Weng, W.; Deng, X.; Cheng, K.; Liu, X.; Du, P.; Shen, G.; Han, G. Dissolution behavior of submicron biphasic tricalcium phosphate powders. Key Eng. Mater. 2006, 309–311, 223–226.
  36. Li, Y.; Weng, W.; Tam, K.C. Novel highly biodegradable biphasic tricalcium phosphates composed of α-tricalcium phosphate and β-tricalcium phosphate. Acta Biomater. 2007, 3, 251–254.
  37. Zou, C.; Cheng, K.; Weng, W.; Song, C.; Du, P.; Shen, G.; Han, G. Characterization and dissolution–reprecipitation behavior of biphasic tricalcium phosphate powders. J. Alloys Compd. 2011, 509, 6852–6858.
  38. Xie, L.; Yu, H.; Deng, Y.; Yang, W.; Liao, L.; Long, Q. Preparation and in vitro degradation study of the porous dual alpha/beta-tricalcium phosphate bioceramics. Mater. Res. Inn. 2016, 20, 530–537.
  39. Albuquerque, J.S.V.; Nogueira, R.E.F.Q.; da Silva, T.D.P.; Lima, D.O.; da Silva, M.H.P. Porous triphasic calcium phosphate bioceramics. Key Eng. Mater. 2004, 254–256, 1021–1024.
  40. Mendonça, F.; Lourom, L.H.L.; de Campos, J.B.; da Silva, M.H.P. Porous biphasic and triphasic bioceramics scaffolds produced by gelcasting. Key Eng. Mater. 2008, 361–363, 27–30.
  41. Vani, R.; Girija, E.K.; Elayaraja, K.; Parthiban, P.S.; Kesavamoorthy, R.; Narayana Kalkura, S. Hydrothermal synthesis of porous triphasic hydroxyapatite/(α and β) tricalcium phosphate. J. Mater. Sci. Mater. Med. 2009, 20 (Suppl. 1), S43–S48.
  42. Ahn, M.K.; Moon, Y.W.; Koh, Y.H.; Kim, H.E. Production of highly porous triphasic calcium phosphate scaffolds with excellent in vitro bioactivity using vacuum-assisted foaming of ceramic suspension (VFC) technique. Ceram. Int. 2013, 39, 5879–5885.
  43. Dorozhkin, S.V. Self-setting calcium orthophosphate (CaPO4) formulations and their biomedical applications. Adv. Nano-Bio. Mater. Dev. 2019, 3, 321–421.
  44. Tamimi, F.; Sheikh, Z.; Barralet, J. Dicalcium phosphate cements: Brushite and monetite. Acta Biomater. 2012, 8, 474–487.
  45. Dorozhkin, S.V. Calcium Orthophosphates: Applications in Nature, Biology, and Medicine; Pan Stanford: Singapore, 2012; p. 850.
  46. LeGeros, R.Z. Calcium phosphates in oral biology and medicine. In Monographs in Oral Science; Karger: Basel, Switzerland, 1991; Volume 15, p. 201.
  47. Narasaraju, T.S.B.; Phebe, D.E. Some physico-chemical aspects of hydroxylapatite. J. Mater. Sci. 1996, 31, 1–21.
  48. Elliott, J.C. Structure and chemistry of the apatites and other calcium orthophosphates. In Studies in Inorganic Chemistry; Elsevier: Amsterdam, The Netherlands, 1994; Volume 18, p. 389.
  49. Brown, P.W.; Constantz, B. (Eds.) Hydroxyapatite and Related Materials; CRC Press: Boca Raton, FL, USA, 1994; p. 343.
  50. Amjad, Z. (Ed.) Calcium Phosphates in Biological and Industrial Systems; Kluwer Academic Publishers: Boston, MA, USA, 1997; p. 529.
  51. Da Silva, R.V.; Bertran, C.A.; Kawachi, E.Y.; Camilli, J.A. Repair of cranial bone defects with calcium phosphate ceramic implant or autogenous bone graft. J. Craniofac. Surg. 2007, 18, 281–286.
  52. Okanoue, Y.; Ikeuchi, M.; Takemasa, R.; Tani, T.; Matsumoto, T.; Sakamoto, M.; Nakasu, M. Comparison of in vivo bioactivity and compressive strength of a novel superporous hydroxyapatite with beta-tricalcium phosphates. Arch. Orthop. Trauma Surg. 2012, 132, 1603–1610.
  53. Draenert, M.; Draenert, A.; Draenert, K. Osseointegration of hydroxyapatite and remodeling-resorption of tricalciumphosphate ceramics. Microsc. Res. Tech. 2013, 76, 370–380.
  54. Zhu, X.D.; Zhang, H.J.; Fan, H.S.; Li, W.; Zhang, X.D. Effect of phase composition and microstructure of calcium phosphate ceramic particles on protein adsorption. Acta Biomater. 2010, 6, 1536–1541.
  55. Bohner, M. Calcium orthophosphates in medicine: From ceramics to calcium phosphate cements. Injury 2000, 31 (Suppl. 4), D37–D47.
  56. Ahato, I. Reverse engineering the ceramic art of algae. Science 1999, 286, 1059–1061.
  57. Popişter, F.; Popescu, D.; Hurgoiu, D. A new method for using reverse engineering in case of ceramic tiles. Qual. Access Success 2012, 13 (Suppl. 5), 409–412.
  58. Yang, S.; Leong, K.F.; Du, Z.; Chua, C.K. The design of scaffolds for use in tissue engineering. Part II. Rapid prototyping techniques. Tissue Eng. 2002, 8, 1–11.
  59. Yeong, W.Y.; Chua, C.K.; Leong, K.F.; Chandrasekaran, M. Rapid prototyping in tissue engineering: Challenges and potential. Trends Biotechnol. 2004, 22, 643–652.
  60. Ortona, A.; D’Angelo, C.; Gianella, S.; Gaia, D. Cellular ceramics produced by rapid prototyping and replication. Mater. Lett. 2012, 80, 95–98.
  61. Eufinger, H.; Wehniöller, M.; Machtens, E.; Heuser, L.; Harders, A.; Kruse, D. Reconstruction of craniofacial bone defects with individual alloplastic implants based on CAD/CAM-manipulated CT-data. J. Cranio Maxillofac. Surg. 1995, 23, 175–181.
  62. Klein, M.; Glatzer, C. Individual CAD/CAM fabricated glass-bioceramic implants in reconstructive surgery of the bony orbital floor. Plastic Reconstruct. Surg. 2006, 117, 565–570.
  63. Yin, L.; Song, X.F.; Song, Y.L.; Huang, T.; Li, J. An overview of in vitro abrasive finishing & CAD/CAM of bioceramics in restorative dentistry. Int. J. Machine Tools Manufact. 2006, 46, 1013–1026.
  64. Li, J.; Hsu, Y.; Luo, E.; Khadka, A.; Hu, J. Computer-aided design and manufacturing and rapid prototyped nanoscale hydroxyapatite/polyamide (n-HA/PA) construction for condylar defect caused by mandibular angle ostectomy. Aesthetic Plast. Surg. 2011, 35, 636–640.
  65. Ciocca, L.; Donati, D.; Fantini, M.; Landi, E.; Piattelli, A.; Iezzi, G.; Tampieri, A.; Spadari, A.; Romagnoli, N.; Scotti, R. CAD-CAM-generated hydroxyapatite scaffold to replace the mandibular condyle in sheep: Preliminary results. J. Biomater. Appl. 2013, 28, 207–218.
  66. Janek, M.; Žilinská, V.; Kovár, V.; Hajdúchová, Z.; Tomanová, K.; Peciar, P.; Veteška, P.; Gabošová, T.; Fialka, R.; Feranc, J.; et al. Mechanical testing of hydroxyapatite filaments for tissue scaffolds preparation by fused deposition of ceramics. J. Eur. Ceram. Soc. 2020, 40, 4932–4938.
  67. Esslinger, S.; Grebhardt, A.; Jaeger, J.; Kern, F.; Killinger, A.; Bonten, C.; Gadow, R. Additive manufacturing of β-tricalcium phosphate components via fused deposition of ceramics (FDC). Materials 2021, 14, 156.
  68. Tan, K.H.; Chua, C.K.; Leong, K.F.; Cheah, C.M.; Cheang, P.; Abu Bakar, M.S.; Cha, S.W. Scaffold development using selective laser sintering of polyetheretherketone-hydroxyapatite biocomposite blends. Biomaterials 2003, 24, 3115–3123.
  69. Wiria, F.E.; Leong, K.F.; Chua, C.K.; Liu, Y. Poly-ε-caprolactone/hydroxyapatite for tissue engineering scaffold fabrication via selective laser sintering. Acta Biomater. 2007, 3, 1–12.
  70. Shuai, C.J.; Li, P.J.; Feng, P.; Lu, H.B.; Peng, S.P.; Liu, J.L. Analysis of transient temperature distribution during the selective laser sintering of β-tricalcium phosphate. Laser Eng. 2013, 26, 71–80.
  71. Shuai, C.; Zhuang, J.; Hu, H.; Peng, S.; Liu, D.; Liu, J. In vitro bioactivity and degradability of β-tricalcium phosphate porous scaffold fabricated via selective laser sintering. Biotechnol. Appl. Biochem. 2013, 60, 266–273.
  72. Qin, T.; Li, X.; Long, H.; Bin, S.; Xu, Y. Bioactive tetracalcium phosphate scaffolds fabricated by selective laser sintering for bone regeneration applications. Materials 2020, 13, 2268.
  73. Bulina, N.V.; Titkov, A.I.; Baev, S.G.; Makarova, S.V.; Khusnutdinov, V.R.; Bessmeltsev, V.P.; Lyakhov, N.Z. Laser sintering of hydroxyapatite for potential fabrication of bioceramic scaffolds. Mater. Today Proc. 2021, 37, 4022–4026.
  74. Lusquiños, F.; Pou, J.; Boutinguiza, M.; Quintero, F.; Soto, R.; León, B.; Pérez-Amor, M. Main characteristics of calcium phosphate coatings obtained by laser cladding. Appl. Surf. Sci. 2005, 247, 486–492.
  75. Wang, D.G.; Chen, C.Z.; Ma, J.; Zhang, G. In situ synthesis of hydroxyapatite coating by laser cladding. Colloid Surf. B 2008, 66, 155–162.
  76. Comesaña, R.; Lusquiños, F.; del Val, J.; Malot, T.; López-Álvarez, M.; Riveiro, A.; Quintero, F.; Boutinguiza, M.; Aubry, P.; de Carlos, A.; et al. Calcium phosphate grafts produced by rapid prototyping based on laser cladding. J. Eur. Ceram. Soc. 2011, 31, 29–41.
  77. Jing, Z.; Cao, Q.; Jun, H. Corrosion, wear and biocompatibility of hydroxyapatite bio-functionally graded coating on titanium alloy surface prepared by laser cladding. Ceram. Int. 2021, 47, 24641–24651.
  78. Vorndran, E.; Klarner, M.; Klammert, U.; Grover, L.M.; Patel, S.; Barralet, J.E.; Gbureck, U. 3D powder printing of β-tricalcium phosphate ceramics using different strategies. Adv. Eng. Mater. 2008, 10, B67–B71.
  79. Leukers, B.; Gülkan, H.; Irsen, S.H.; Milz, S.; Tille, C.; Schieker, M.; Seitz, H. Hydroxyapatite scaffolds for bone tissue engineering made by 3D printing. J. Mater. Sci. Mater. Med. 2005, 16, 1121–1124.
  80. Gbureck, U.; Hölzel, T.; Klammert, U.; Würzler, K.; Müller, F.A.; Barralet, J.E. Resorbable dicalcium phosphate bone substitutes prepared by 3D powder printing. Adv. Funct. Mater. 2007, 17, 3940–3945.
  81. Seitz, H.; Deisinger, U.; Leukers, B.; Detsch, R.; Ziegler, G. Different calcium phosphate granules for 3-D printing of bone tissue engineering scaffolds. Adv. Eng. Mater. 2009, 11, B41–B46.
  82. Butscher, A.; Bohner, M.; Roth, C.; Ernstberger, A.; Heuberger, R.; Doebelin, N.; von Rohr, R.P.; Müller, R. Printability of calcium phosphate powders for three-dimensional printing of tissue engineering scaffolds. Acta Biomater. 2012, 8, 373–385.
  83. Akkineni, A.R.; Luo, Y.; Schumacher, M.; Nies, B.; Lode, A.; Gelinsky, M. 3D plotting of growth factor loaded calcium phosphate cement scaffolds. Acta Biomater. 2015, 27, 264–274.
  84. Trombetta, R.; Inzana, J.A.; Schwarz, E.M.; Kates, S.L.; Awad, H.A. 3D printing of calcium phosphate ceramics for bone tissue engineering and drug delivery. Ann. Biomed. Eng. 2017, 45, 23–44.
  85. Ma, H.; Feng, C.; Chang, J.; Wu, C. 3D-printed bioceramic scaffolds: From bone tissue engineering to tumor therapy. Acta Biomater. 2018, 79, 37–59.
  86. Miranda, P.; Pajares, A.; Saiz, E.; Tomsia, A.P.; Guiberteau, F. Mechanical behaviour under uniaxial compression of robocast calcium phosphate scaffolds. Eur. Cells Mater. 2007, 14 (Suppl. 1), 79.
  87. Maazouz, Y.; Montufar, E.B.; Guillem-Marti, J.; Fleps, I.; Öhman, C.; Persson, C.; Ginebra, M.P. Robocasting of biomimetic hydroxyapatite scaffolds using self-setting inks. J. Mater. Chem. B 2014, 2, 5378–5386.
  88. Liu, Q.; Lu, W.F.; Zhai, W. Toward stronger robocast calcium phosphate scaffolds for bone tissue engineering: A mini-review and meta-analysis. Biomater. Adv. 2022, 134, 112578.
  89. Porter, N.L.; Pilliar, R.M.; Grynpas, M.D. Fabrication of porous calcium polyphosphate implants by solid freeform fabrication: A study of processing parameters and in vitro degradation characteristics. J. Biomed. Mater. Res. 2001, 56, 504–515.
  90. Leong, K.F.; Cheah, C.M.; Chua, C.K. Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. Biomaterials 2003, 24, 2363–2378.
  91. Shanjani, Y.; de Croos, J.N.A.; Pilliar, R.M.; Kandel, R.A.; Toyserkani, E. Solid freeform fabrication and characterization of porous calcium polyphosphate structures for tissue engineering purposes. J. Biomed. Mater. Res. B Appl. Biomater. 2010, 93B, 510–519.
  92. Kim, J.; Lim, D.; Kim, Y.H.; Koh, Y.H.; Lee, M.H.; Han, I.; Lee, S.J.; Yoo, O.S.; Kim, H.S.; Park, J.C. A comparative study of the physical and mechanical properties of porous hydroxyapatite scaffolds fabricated by solid freeform fabrication and polymer replication method. Int. J. Precision Eng. Manuf. 2011, 12, 695–701.
  93. Shanjani, Y.; Hu, Y.; Toyserkani, E.; Grynpas, M.; Kandel, R.A.; Pilliar, R.M. Solid freeform fabrication of porous calcium polyphosphate structures for bone substitute applications: In vivo studies. J. Biomed. Mater. Res. B Appl. Biomater. 2013, 101B, 972–980.
  94. Kwon, B.J.; Kim, J.; Kim, Y.H.; Lee, M.H.; Baek, H.S.; Lee, D.H.; Kim, H.L.; Seo, H.J.; Lee, M.H.; Kwon, S.Y.; et al. Biological advantages of porous hydroxyapatite scaffold made by solid freeform fabrication for bone tissue regeneration. Artif. Organs 2013, 37, 663–670.
  95. Li, X.; Li, D.; Lu, B.; Wang, C. Fabrication of bioceramic scaffolds with pre-designed internal architecture by gel casting and indirect stereolithography techniques. J. Porous Mater. 2008, 15, 667–671.
  96. Ronca, A.; Ambrosio, L.; Grijpma, D.W. Preparation of designed poly(D,L-lactide)/nanosized hydroxyapatite composite structures by stereolithography. Acta Biomater. 2013, 9, 5989–5996.
  97. Wei, Y.; Zhao, D.; Cao, Q.; Wang, J.; Wu, Y.; Yuan, B.; Li, X.; Chen, X.; Zhou, Y.; Yang, X.; et al. Stereolithography-based additive manufacturing of high-performance osteoinductive calcium phosphate ceramics by a digital light-processing system. ACS Biomater. Sci. Eng. 2020, 6, 1787–1797.
  98. Ullah, I.; Cao, L.; Cui, W.; Xu, Q.; Yang, R.; Tang, K.L.; Zhang, X. Stereolithography printing of bone scaffolds using biofunctional calcium phosphate nanoparticles. J. Mater. Sci. Technol. 2021, 88, 99–108.
  99. Paredes, C.; Martínez-Vázquez, F.J.; Elsayed, H.; Colombo, P.; Pajares, A.; Miranda, P. Evaluation of direct light processing for the fabrication of bioactive ceramic scaffolds: Effect of pore/strut size on manufacturability and mechanical performance. J. Eur. Ceram. Soc. 2021, 41, 892–900.
  100. Gladman, A.S.; Matsumoto, E.A.; Nuzzo, R.G.; Mahadevan, L.; Lewis, J.A. Biomimetic 4D printing. Nat. Mater. 2016, 15, 413–418.
  101. Hwangbo, H.; Lee, H.; Roh, E.J.; Kim, W.; Joshi, H.P.; Kwon, S.Y.; Choi, U.Y.; Han, I.B.; Kim, G.H. Bone tissue engineering via application of a collagen/hydroxyapatite 4D-printed biomimetic scaffold for spinal fusion. Appl. Phys. Rev. 2021, 8, 021403.
  102. Haleem, A.; Javaid, M.; Vaishya, R. 5D printing and its expected applications in orthopaedics. J. Clin. Orthop. Trauma. 2019, 10, 809–810.
  103. Du, X.; Fu, S.; Zhu, Y. 3D printing of ceramic-based scaffolds for bone tissue engineering: An overview. J. Mater. Chem. B 2018, 6, 4397–4412.
  104. Kumar, A.; Kargozar, S.; Baino, F.; Han, S.S. Additive manufacturing methods for producing hydroxyapatite and hydroxyapatite-based composite scaffolds: A review. Front. Mater. 2019, 6, 313.
  105. Chen, Z.; Li, Z.; Li, J.; Liu, C.; Lao, C.; Lao, C.; Fu, Y.; Liu, C.; Li, Y.; Wang, P.; et al. 3D printing of ceramics: A review. J. Eur. Ceram. Soc. 2019, 39, 661–687.
  106. Qu, H. Additive manufacturing for bone tissue engineering scaffolds. Mater. Today Commun. 2020, 24, 101024.
  107. Kokubo, T. (Ed.) Bioceramics and Their Clinical Applications; Woodhead Publishing: Cambridge, UK, 2008; p. 784.
  108. Narayan, R. (Ed.) Biomedical Materials; Springer: New York, NY, USA, 2009; p. 566.
  109. Park, J. Bioceramics: Properties, Characterizations, and Applications; Springer: New York, NY, USA, 2008; p. 364.
  110. Rodríguez-Lorenzo, L.M.; Vallet-Regí, M.; Ferreira, J.M.F. Fabrication of hydroxyapatite bodies by uniaxial pressing from a precipitated powder. Biomaterials 2001, 22, 583–588.
  111. Indra, A.; Putra, A.B.; Handra, N.; Fahmi, H.; Nurzal; Asfarizal; Perdana, M.; Anrinal; Subardi, A.; Affi, J.; et al. Behavior of sintered body properties of hydroxyapatite ceramics: Effect of uniaxial pressure on green body fabrication. Mater. Today Sustain. 2022, 17, 100100.
  112. Uematsu, K.; Takagi, M.; Honda, T.; Uchida, N.; Saito, K. Transparent hydroxyapatite prepared by hot isostatic pressing of filter cake. J. Am. Ceram. Soc. 1989, 72, 1476–1478.
  113. Itoh, H.; Wakisaka, Y.; Ohnuma, Y.; Kuboki, Y. A new porous hydroxyapatite ceramic prepared by cold isostatic pressing and sintering synthesized flaky powder. Dent. Mater. 1994, 13, 25–35.
  114. Takikawa, K.; Akao, M. Fabrication of transparent hydroxyapatite and application to bone marrow derived cell/hydroxyapatite interaction observation in-vivo. J. Mater. Sci. Mater. Med. 1996, 7, 439–445.
  115. Gautier, H.; Merle, C.; Auget, J.L.; Daculsi, G. Isostatic compression, a new process for incorporating vancomycin into biphasic calcium phosphate: Comparison with a classical method. Biomaterials 2000, 21, 243–249.
  116. Tadic, D.; Epple, M. Mechanically stable implants of synthetic bone mineral by cold isostatic pressing. Biomaterials 2003, 24, 4565–4571.
  117. Onoki, T.; Hashida, T. New method for hydroxyapatite coating of titanium by the hydrothermal hot isostatic pressing technique. Surf. Coat. Technol. 2006, 200, 6801–6807.
  118. Ehsani, N.; Ruys, A.J.; Sorrell, C.C. Hot isostatic pressing (HIPing) of fecralloy-reinforced hydroxyapatite. J. Biomimet. Biomater. Tissue Eng. 2013, 17, 87–102.
  119. Irsen, S.H.; Leukers, B.; Höckling, C.; Tille, C.; Seitz, H. Bioceramic granulates for use in 3D printing: Process engineering aspects. Materwiss. Werksttech. 2006, 37, 533–537.
  120. Hsu, Y.H.; Turner, I.G.; Miles, A.W. Fabrication and mechanical testing of porous calcium phosphate bioceramic granules. J. Mater. Sci. Mater. Med. 2007, 18, 1931–1937.
  121. Zyman, Z.Z.; Glushko, V.; Dedukh, N.; Malyshkina, S.; Ashukina, N. Porous calcium phosphate ceramic granules and their behaviour in differently loaded areas of skeleton. J. Mater. Sci. Mater. Med. 2008, 19, 2197–2205.
  122. Viana, M.; Désiré, A.; Chevalier, E.; Champion, E.; Chotard, R.; Chulia, D. Interest of high shear wet granulation to produce drug loaded porous calcium phosphate pellets for bone filling. Key Eng. Mater. 2009, 396–398, 535–538.
  123. Chevalier, E.; Viana, M.; Cazalbou, S.; Chulia, D. Comparison of low-shear and high-shear granulation processes: Effect on implantable calcium phosphate granule properties. Drug Dev. Ind. Pharm. 2009, 35, 1255–1263.
  124. 197 Lakevics, V.; Locs, J.; Loca, D.; Stepanova, V.; Berzina-Cimdina, L.; Pelss, J. Bioceramic hydroxyapatite granules for purification of biotechnological products. Adv. Mater. Res. 2011, 284–286, 1764–1769.
  125. Camargo, N.H.A.; Franczak, P.F.; Gemelli, E.; da Costa, B.D.; de Moraes, A.N. Characterization of three calcium phosphate microporous granulated bioceramics. Adv. Mater. Res. 2014, 936, 687–694.
  126. Reikerås, O.; Johansson, C.B.; Sundfeldt, M. Bone ingrowths to press-fit and loose-fit implants: Comparisons between titanium and hydroxyapatite. J. Long-Term Eff. Med. Implant. 2006, 16, 157–164.
  127. Liu, Y.; Kim, J.H.; Young, D.; Kim, S.; Nishimoto, S.K.; Yang, Y. Novel template-casting technique for fabricating β-tricalcium phosphate scaffolds with high interconnectivity and mechanical strength and in vitro cell responses. J. Biomed. Mater. Res. A 2010, 92A, 997–1006.
  128. Rao, R.R.; Kannan, T.S. Dispersion and slip casting of hydroxyapatite. J. Am. Ceram. Soc. 2001, 84, 1710–1716.
  129. Sakka, Y.; Takahashi, K.; Matsuda, N.; Suzuki, T.S. Effect of milling treatment on texture development of hydroxyapatite ceramics by slip casting in high magnetic field. Mater. Trans. 2007, 48, 2861–2866.
  130. Zhang, Y.; Yokogawa, Y.; Feng, X.; Tao, Y.; Li, Y. Preparation and properties of bimodal porous apatite ceramics through slip casting using different hydroxyapatite powders. Ceram. Int. 2010, 36, 107–113.
  131. Zhang, Y.; Kong, D.; Yokogawa, Y.; Feng, X.; Tao, Y.; Qiu, T. Fabrication of porous hydroxyapatite ceramic scaffolds with high flexural strength through the double slip-casting method using fine powders. J. Am. Ceram. Soc. 2012, 95, 147–152.
  132. Hagio, T.; Yamauchi, K.; Kohama, T.; Matsuzaki, T.; Iwai, K. Beta tricalcium phosphate ceramics with controlled crystal orientation fabricated by application of external magnetic field during the slip casting process. Mater. Sci. Eng. C 2013, 33, 2967–2970.
  133. Marçal, R.L.S.B.; da Rocha, D.N.; da Silva, M.H.P. Slip casting used as a forming technique for hydroxyapatite processing. Key Eng. Mater. 2017, 720, 219–222.
  134. Sepulveda, P.; Ortega, F.S.; Innocentini, M.D.M.; Pandolfelli, V.C. Properties of highly porous hydroxyapatite obtained by the gel casting of foams. J. Am. Ceram. Soc. 2000, 83, 3021–3024.
  135. Sánchez-Salcedo, S.; Werner, J.; Vallet-Regí, M. Hierarchical pore structure of calcium phosphate scaffolds by a combination of gel-casting and multiple tape-casting methods. Acta Biomater. 2008, 4, 913–922.
  136. Chen, B.; Zhang, T.; Zhang, J.; Lin, Q.; Jiang, D. Microstructure and mechanical properties of hydroxyapatite obtained by gel-casting process. Ceram. Int. 2008, 34, 359–364.
  137. Marcassoli, P.; Cabrini, M.; Tirillò, J.; Bartuli, C.; Palmero, P.; Montanaro, L. Mechanical characterization of hydroxiapatite micro/macro-porous ceramics obtained by means of innovative gel-casting process. Key Eng. Mater. 2010, 417–418, 565–568.
  138. Dash, S.R.; Sarkar, R.; Bhattacharyya, S. Gel casting of hydroxyapatite with naphthalene as pore former. Ceram. Int. 2015, 41, 3775–3790.
  139. Ramadas, M.; Ferreira, J.M.F.; Ballamurugan, A.M. Fabrication of three dimensional bioactive Sr2+ substituted apatite scaffolds by gel-casting technique for hard tissue regeneration. J. Tissue Eng. Regen. Med. 2021, 15, 577–585.
  140. Fomin, A.S.; Barinov, S.M.; Ievlev, V.M.; Smirnov, V.V.; Mikhailov, B.P.; Belonogov, E.K.; Drozdova, N.A. Nanocrystalline hydroxyapatite ceramics produced by low-temperature sintering after high-pressure treatment. Dokl. Chem. 2008, 418, 22–25.
  141. Zhang, J.; Yin, H.M.; Hsiao, B.S.; Zhong, G.J.; Li, Z.M. Biodegradable poly(lactic acid)/hydroxyl apatite 3D porous scaffolds using high-pressure molding and salt leaching. J. Mater. Sci. 2014, 49, 1648–1658.
  142. Zhang, J.; Liu, H.; Ding, J.X.; Wu, J.; Zhuang, X.; Chen, X.; Wang, J.; Yin, J.; Li, Z. High-pressure compression-molded porous resorbable polymer/hydroxyapatite composite scaffold for cranial bone regeneration. ACS Biomater. Sci. Eng. 2016, 2, 1471–1482.
  143. Kankawa, Y.; Kaneko, Y.; Saitou, K. Injection molding of highly-purified hydroxylapatite and TCP utilizing solid phase reaction method. J. Ceram. Soc. Jpn. 1991, 99, 438–442.
  144. Cihlář, J.; Trunec, M. Injection moulded hydroxyapatite ceramics. Biomaterials 1996, 17, 1905–1911.
  145. Jewad, R.; Bentham, C.; Hancock, B.; Bonfield, W.; Best, S.M. Dispersant selection for aqueous medium pressure injection moulding of anhydrous dicalcium phosphate. J. Eur. Ceram. Soc. 2008, 28, 547–553.
  146. McNamara, S.L.; McCarthy, E.M.; Schmidt, D.F.; Johnston, S.P.; Kaplan, D.L. Rheological characterization, compression, and injection molding of hydroxyapatite-silk fibroin composites. Biomaterials 2021, 269, 120643.
  147. Kwon, S.H.; Jun, Y.K.; Hong, S.H.; Lee, I.S.; Kim, H.E.; Won, Y.Y. Calcium phosphate bioceramics with various porosities and dissolution rates. J. Am. Ceram. Soc. 2002, 85, 3129–3131.
  148. Fooki, A.C.B.M.; Aparecida, A.H.; Fideles, T.B.; Costa, R.C.; Fook, M.V.L. Porous hydroxyapatite scaffolds by polymer sponge method. Key Eng. Mater. 2009, 396–398, 703–706.
  149. Sopyan, I.; Kaur, J. Preparation and characterization of porous hydroxyapatite through polymeric sponge method. Ceram. Int. 2009, 35, 3161–3168.
  150. Bellucci, D.; Cannillo, V.; Sola, A. Shell scaffolds: A new approach towards high strength bioceramic scaffolds for bone regeneration. Mater. Lett. 2010, 64, 203–206.
  151. Cunningham, E.; Dunne, N.; Walker, G.; Maggs, C.; Wilcox, R.; Buchanan, F. Hydroxyapatite bone substitutes developed via replication of natural marine sponges. J. Mater. Sci. Mater. Med. 2010, 21, 2255–2261.
  152. Sung, J.H.; Shin, K.H.; Koh, Y.H.; Choi, W.Y.; Jin, Y.; Kim, H.E. Preparation of the reticulated hydroxyapatite ceramics using carbon-coated polymeric sponge with elongated pores as a novel template. Ceram. Int. 2011, 37, 2591–2596.
  153. Mishima, F.D.; Louro, L.H.L.; Moura, F.N.; Gobbo, L.A.; da Silva, M.H.P. Hydroxyapatite scaffolds produced by hydrothermal deposition of monetite on polyurethane sponges substrates. Key Eng. Mater. 2012, 493–494, 820–825.
  154. Hannickel, A.; da Silva, M.H.P. Novel bioceramic scaffolds for regenerative medicine. Bioceram. Dev. Appl. 2015, 5, 1000082.
  155. Das, S.; Kumar, S.; Doloi, B.; Bhattacharyya, B. Experimental studies of ultrasonic machining on hydroxyapatite bio-ceramics. Int. J. Adv. Manuf. Tech. 2016, 86, 829–839.
  156. Velayudhan, S.; Ramesh, P.; Sunny, M.C.; Varma, H.K. Extrusion of hydroxyapatite to clinically significant shapes. Mater. Lett. 2000, 46, 142–146.
  157. Yang, H.Y.; Thompson, I.; Yang, S.F.; Chi, X.P.; Evans, J.R.G.; Cook, R.J. Dissolution characteristics of extrusion freeformed hydroxyapatite–tricalcium phosphate scaffolds. J. Mater. Sci. Mater. Med. 2008, 19, 3345–3353.
  158. Yang, S.; Yang, H.; Chi, X.; Evans, J.R.G.; Thompson, I.; Cook, R.J.; Robinson, P. Rapid prototyping of ceramic lattices for hard tissue scaffolds. Mater. Des. 2008, 29, 1802–1809.
  159. Yang, H.Y.; Chi, X.P.; Yang, S.; Evans, J.R.G. Mechanical strength of extrusion freeformed calcium phosphate filaments. J. Mater. Sci. Mater. Med. 2010, 21, 1503–1510.
  160. Cortez, P.P.; Atayde, L.M.; Silva, M.A.; da Silva, P.A.; Fernandes, M.H.; Afonso, A.; Lopes, M.A.; Maurício, A.C.; Santos, J.D. Characterization and preliminary in vivo evaluation of a novel modified hydroxyapatite produced by extrusion and spheronization techniques. J. Biomed. Mater. Res. B Appl. Biomater. 2011, 99B, 170–179.
  161. Lim, S.; Chun, S.; Yang, D.; Kim, S. Comparison study of porous calcium phosphate blocks prepared by piston and screw type extruders for bone scaffold. Tissue Eng. Regen. Med. 2012, 9, 51–55.
  162. Blake, D.M.; Tomovic, S.; Jyung, R.W. Extrusion of hydroxyapatite ossicular prosthesis. Ear Nose Throat J. 2013, 92, 490–494.
  163. Muthutantri, A.I.; Huang, J.; Edirisinghe, M.J.; Bretcanu, O.; Boccaccini, A.R. Dipping and electrospraying for the preparation of hydroxyapatite foams for bone tissue engineering. Biomed. Mater. 2008, 3, 25009.
  164. Roncari, E.; Galassi, C.; Pinasco, P. Tape casting of porous hydroxyapatite ceramics. J. Mater. Sci. Lett. 2000, 19, 33–35.
  165. Tian, T.; Jiang, D.; Zhang, J.; Lin, Q. Aqueous tape casting process for hydroxyapatite. J. Eur. Ceram. Soc. 2007, 27, 2671–2677.
  166. Tanimoto, Y.; Shibata, Y.; Murakami, A.; Miyazaki, T.; Nishiyama, N. Effect of varying HAP/TCP ratios in tape-cast biphasic calcium phosphate ceramics on responcce in vitro. J. Hard Tiss. Biol. 2009, 18, 71–76.
  167. Tanimoto, Y.; Teshima, M.; Nishiyama, N.; Yamaguchi, M.; Hirayama, S.; Shibata, Y.; Miyazaki, T. Tape-cast and sintered β-tricalcium phosphate laminates for biomedical applications: Effect of milled Al2O3 fiber additives on microstructural and mechanical properties. J. Biomed. Mater. Res. B Appl. Biomater. 2012, 100B, 2261–2268.
  168. Khamkasem, C.; Chaijaruwanich, A. Effect of binder/plasticizer ratios in aqueous-based tape casting on mechanical properties of bovine hydroxyapatite tape. Ferroelectrics 2013, 455, 129–135.
  169. Suzuki, S.; Itoh, K.; Ohgaki, M.; Ohtani, M.; Ozawa, M. Preparation of sintered filter for ion exchange by a doctor blade method with aqueous slurries of needlelike hydroxyapatite. Ceram. Int. 1999, 25, 287–291.
  170. Nishikawa, H.; Hatanaka, R.; Kusunoki, M.; Hayami, T.; Hontsu, S. Preparation of freestanding hydroxyapatite membranes excellent biocompatibility and flexibility. Appl. Phys. Express 2008, 1, 088001.
  171. Kim, I.Y.; Wen, J.; Ohtsuki, C. Fabrication of α-tricalcium phosphate ceramics through two-step sintering. Key Eng. Mater. 2015, 631, 78–82.
  172. Padilla, S.; Roman, J.; Vallet-Regí, M. Synthesis of porous hydroxyapatites by combination of gel casting and foams burn out methods. J. Mater. Sci. Mater. Med. 2002, 13, 1193–1197.
  173. Yang, T.Y.; Lee, J.M.; Yoon, S.Y.; Park, H.C. Hydroxyapatite scaffolds processed using a TBA-based freeze-gel casting/polymer sponge technique. J. Mater. Sci. Mater. Med. 2010, 21, 1495–1502.
  174. Baradararan, S.; Hamdi, M.; Metselaar, I.H. Biphasic calcium phosphate (BCP) macroporous scaffold with different ratios of HA/β-TCP by combination of gel casting and polymer sponge methods. Adv. Appl. Ceram. 2012, 111, 367–373.
  175. Inoue, K.; Sassa, K.; Yokogawa, Y.; Sakka, Y.; Okido, M.; Asai, S. Control of crystal orientation of hydroxyapatite by imposition of a high magnetic field. Mater. Trans. 2003, 44, 1133–1137.
  176. Iwai, K.; Akiyama, J.; Tanase, T.; Asai, S. Alignment of HAp crystal using a sample rotation in a static magnetic field. Mater. Sci. Forum. 2007, 539–543, 716–719.
  177. Iwai, K.; Akiyama, J.; Asai, S. Structure control of hydroxyapatite using a magnetic field. Mater. Sci. Forum. 2007, 561–565, 1565–1568.
  178. Sakka, Y.; Takahashi, K.; Suzuki, T.S.; Ito, S.; Matsuda, N. Texture development of hydroxyapatite ceramics by colloidal processing in a high magnetic field followed by sintering. Mater. Sci. Eng. A 2008, 475, 27–33.
  179. Fleck, N.A. On the cold compaction of powders. J. Mech. Phys. Solids 1995, 43, 1409–1431.
  180. Kang, J.; Hadfield, M. Parameter optimization by Taguchi methods for finishing advanced ceramic balls using a novel eccentric lapping machine. Proc. Inst. Mech. Eng. B 2001, 215, 69–78.
  181. Kulkarni, S.S.; Yong, Y.; Rys, M.J.; Lei, S. Machining assessment of nano-crystalline hydroxyapatite bio-ceramic. J. Manuf. Processes 2013, 15, 666–672.
  182. Kurella, A.; Dahotre, N.B. Surface modification for bioimplants: The role of laser surface engineering. J. Biomater. Appl. 2005, 20, 5–50.
  183. Moriguchi, Y.; Lee, D.S.; Chijimatsu, R.; Thamina, K.; Masuda, K.; Itsuki, D.; Yoshikawa, H.; Hamaguchi, S.; Myoui, A. Impact of non-thermal plasma surface modification on porous calcium hydroxyapatite ceramics for bone regeneration. PLoS ONE 2018, 13, e0194303.
  184. Bertol, L.S.; Schabbach, R.; dos Santos, L.A.L. Different post-processing conditions for 3D bioprinted α-tricalcium phosphate scaffolds. J. Mater. Sci. Mater. Med. 2017, 28, 168.
  185. Oktar, F.N.; Genc, Y.; Goller, G.; Erkmen, E.Z.; Ozyegin, L.S.; Toykan, D.; Demirkiran, H.; Haybat, H. Sintering of synthetic hydroxyapatite compacts. Key Eng. Mater. 2004, 264–268, 2087–2090.
  186. Georgiou, G.; Knowles, J.C.; Barralet, J.E. Dynamic shrinkage behavior of hydroxyapatite and glass-reinforced hydroxyapatites. J. Mater. Sci. 2004, 39, 2205–2208.
  187. Fellah, B.H.; Layrolle, P. Sol-gel synthesis and characterization of macroporous calcium phosphate bioceramics containing microporosity. Acta Biomater. 2009, 5, 735–742.
  188. Kutty, M.G.; Bhaduri, S.B.; Zhou, H.; Yaghoubi, A. In situ measurement of shrinkage and temperature profile in microwave- and conventionally-sintered hydroxyapatite bioceramic. Mater. Lett. 2015, 161, 375–378.
  189. Ben Ayed, F.; Bouaziz, J.; Bouzouita, K. Pressureless sintering of fluorapatite under oxygen atmosphere. J. Eur. Ceram. Soc. 2000, 20, 1069–1076.
  190. He, Z.; Ma, J.; Wang, C. Constitutive modeling of the densification and the grain growth of hydroxyapatite ceramics. Biomaterials 2005, 26, 1613–1621.
  191. Rahaman, M.N. Sintering of Ceramics; CRC Press: Boca Raton, FL, USA, 2007; p. 388.
  192. Monroe, E.A.; Votava, W.; Bass, D.B.; McMullen, J. New calcium phosphate ceramic material for bone and tooth implants. J. Dent. Res. 1971, 50, 860–861.
  193. Landi, E.; Tampieri, A.; Celotti, G.; Sprio, S. Densification behaviour and mechanisms of synthetic hydroxyapatites. J. Eur. Ceram. Soc. 2000, 20, 2377–2387.
  194. Döbelin, N.; Maazouz, Y.; Heuberger, R.; Bohner, M.; Armstrong, A.A.; Wagoner Johnson, A.J.; Wanner, C. A thermodynamic approach to surface modification of calcium phosphate implants by phosphate evaporation and condensation. J. Eur. Ceram. Soc. 2020, 40, 6095–6106.
  195. Chen, S.; Wang, W.; Kono, H.; Sassa, K.; Asai, S. Abnormal grain growth of hydroxyapatite ceramic sintered in a high magnetic field. J. Cryst. Growth 2010, 312, 323–326.
  196. Ruys, A.J.; Wei, M.; Sorrell, C.C.; Dickson, M.R.; Brandwood, A.; Milthorpe, B.K. Sintering effect on the strength of hydroxyapatite. Biomaterials 1995, 16, 409–415.
  197. Van Landuyt, P.; Li, F.; Keustermans, J.P.; Streydio, J.M.; Delannay, F.; Munting, E. The influence of high sintering temperatures on the mechanical properties of hydroxylapatite. J. Mater. Sci. Mater. Med. 1995, 6, 8–13.
  198. Pramanik, S.; Agarwal, A.K.; Rai, K.N.; Garg, A. Development of high strength hydroxyapatite by solid-state-sintering process. Ceram. Int. 2007, 33, 419–426.
  199. Haberko, K.; Bućko, M.M.; Brzezińska-Miecznik, J.; Haberko, M.; Mozgawa, W.; Panz, T.; Pyda, A.; Zarebski, J. Natural hydroxyapatite–its behaviour during heat treatment. J. Eur. Ceram. Soc. 2006, 26, 537–542.
  200. Haberko, K.; Bućko, M.M.; Mozgawa, W.; Pyda, A.; Brzezińska-Miecznik, J.; Carpentier, J. Behaviour of bone origin hydroxyapatite at elevated temperatures and in O2 and CO2 atmospheres. Ceram. Int. 2009, 35, 2537–2540.
  201. Janus, A.M.; Faryna, M.; Haberko, K.; Rakowska, A.; Panz, T. Chemical and microstructural characterization of natural hydroxyapatite derived from pig bones. Mikrochim. Acta 2008, 161, 349–353.
  202. Bahrololoom, M.E.; Javidi, M.; Javadpour, S.; Ma, J. Characterisation of natural hydroxyapatite extracted from bovine cortical bone ash. J. Ceram. Process. Res. 2009, 10, 129–138.
  203. Mostafa, N.Y. Characterization, thermal stability and sintering of hydroxyapatite powders prepared by different routes. Mater. Chem. Phys. 2005, 94, 333–341.
  204. Suchanek, W.; Yashima, M.; Kakihana, M.; Yoshimura, M. Hydroxyapatite ceramics with selected sintering additives. Biomaterials 1997, 18, 923–933.
  205. Kalita, S.J.; Bose, S.; Bandyopadhyay, A.; Hosick, H.L. Oxide based sintering additives for HAp ceramics. Ceram. Trans. 2003, 147, 63–72.
  206. Kalita, S.J.; Bose, S.; Hosick, H.L.; Bandyopadhyay, A. CaO–P2O5–Na2O-based sintering additives for hydroxyapatite (HAp) ceramics. Biomaterials 2004, 25, 2331–2339.
  207. Safronova, T.V.; Putlyaev, V.I.; Shekhirev, M.A.; Tretyakov, Y.D.; Kuznetsov, A.V.; Belyakov, A.V. Densification additives for hydroxyapatite ceramics. J. Eur. Ceram. Soc. 2009, 29, 1925–1932.
  208. Eskandari, A.; Aminzare, M.; Hassani, H.; Barounian, H.; Hesaraki, S.; Sadrnezhaad, S.K. Densification behavior and mechanical properties of biomimetic apatite nanocrystals. Curr. Nanosci. 2011, 7, 776–780.
  209. Ramesh, S.; Tolouei, R.; Tan, C.Y.; Aw, K.L.; Yeo, W.H.; Sopyan, I.; Teng, W.D. Sintering of hydroxyapatite ceramic produced by wet chemical method. Adv. Mater. Res. 2011, 264–265, 1856–1861.
  210. Ou, S.F.; Chiou, S.Y.; Ou, K.L. Phase transformation on hydroxyapatite decomposition. Ceram. Int. 2013, 39, 3809–3816.
  211. Bernache-Assollant, D.; Ababou, A.; Champion, E.; Heughebaert, M. Sintering of calcium phosphate hydroxyapatite Ca10(PO4)6(OH)2 I. Calcination and particle growth. J. Eur. Ceram. Soc. 2003, 23, 229–241.
  212. Ramesh, S.; Tan, C.Y.; Bhaduri, S.B.; Teng, W.D.; Sopyan, I. Densification behaviour of nanocrystalline hydroxyapatite bioceramics. J. Mater. Process. Technol. 2008, 206, 221–230.
  213. Wang, J.; Shaw, L.L. Grain-size dependence of the hardness of submicrometer and nanometer hydroxyapatite. J. Am. Ceram. Soc. 2010, 93, 601–604.
  214. Kobayashi, S.; Kawai, W.; Wakayama, S. The effect of pressure during sintering on the strength and the fracture toughness of hydroxyapatite ceramics. J. Mater. Sci. Mater. Med. 2006, 17, 1089–1093.
  215. Chen, I.W.; Wang, X.H. Sintering dense nanocrystalline ceramics without final-stage grain growth. Nature 2000, 404, 168–170.
  216. Mazaheri, M.; Haghighatzadeh, M.; Zahedi, A.M.; Sadrnezhaad, S.K. Effect of a novel sintering process on mechanical properties of hydroxyapatite ceramics. J. Alloys Compd. 2009, 471, 180–184.
  217. Panyata, S.; Eitssayeam, S.; Rujijanagul, G.; Tunkasiri, T.; Pengpat, K. Property development of hydroxyapatite ceramics by two-step sintering. Adv. Mater. Res. 2012, 506, 190–193.
  218. Esnaashary, M.; Fathi, M.; Ahmadian, M. The effect of the two-step sintering process on consolidation of fluoridated hydroxyapatite and its mechanical properties and bioactivity. Int. J. Appl. Ceram. Technol. 2014, 11, 47–56.
  219. Feng, P.; Niu, M.; Gao, C.; Peng, S.; Shuai, C. A novel two-step sintering for nano-hydroxyapatite scaffolds for bone tissue engineering. Sci. Rep. 2014, 4, 5599.
  220. Nakahira, A.; Murakami, T.; Onoki, T.; Hashida, T.; Hosoi, K. Fabrication of porous hydroxyapatite using hydrothermal hot pressing and post-sintering. J. Am. Ceram. Soc. 2005, 88, 1334–1336.
  221. Auger, M.A.; Savoini, B.; Muñoz, A.; Leguey, T.; Monge, M.A.; Pareja, R.; Victoria, J. Mechanical characteristics of porous hydroxyapatite/oxide composites produced by post-sintering hot isostatic pressing. Ceram. Int. 2009, 35, 2373–2380.
  222. Guo, N.; Shen, H.Z.; Jin, Q.; Shen, P. Hydrated precursor-assisted densification of hydroxyapatite and its composites by cold sintering. Ceram. Int. 2020, 47, 14348–14353.
  223. Silva, C.C.; Graça, M.P.F.; Sombra, A.S.B.; Valente, M.A. Structural and electrical study of calcium phosphate obtained by a microwave radiation assisted procedure. Phys. Rev. B Condens. Matter 2009, 404, 1503–1508.
  224. Veljović, D.; Zalite, I.; Palcevskis, E.; Smiciklas, I.; Petrović, R.; Janaćković, D. Microwave sintering of fine grained HAP and HAP/TCP bioceramics. Ceram. Int. 2010, 36, 595–603.
  225. Veljović, D.; Palcevskis, E.; Dindune, A.; Putić, S.; Balać, I.; Petrović, R.; Janaćković, D. Microwave sintering improves the mechanical properties of biphasic calcium phosphates from hydroxyapatite microspheres produced from hydrothermal processing. J. Mater. Sci. 2010, 45, 3175–3183.
  226. Tarafder, S.; Balla, V.K.; Davies, N.M.; Bandyopadhyay, A.; Bose, S. Microwave-sintered 3D printed tricalcium phosphate scaffolds for bone tissue engineering. J. Tissue Eng. Regen. Med. 2013, 7, 631–641.
  227. Thuault, A.; Savary, E.; Hornez, J.C.; Moreau, G.; Descamps, M.; Marinel, S.; Leriche, A. Improvement of the hydroxyapatite mechanical properties by direct microwave sintering in single mode cavity. J. Eur. Ceram. Soc. 2014, 34, 1865–1871.
  228. Sikder, P.; Ren, Y.; Bhaduri, S.B. Microwave processing of calcium phosphate and magnesium phosphate based orthopedic bioceramics: A state-of-the-art review. Acta Biomater. 2020, 111, 29–53.
  229. Frasnelli, M.; Sglavo, V.M. Flash sintering of tricalcium phosphate (TCP) bioceramics. J. Eur. Ceram. Soc. 2018, 38, 279–285.
  230. Hwang, C.; Yun, J. Flash sintering of hydroxyapatite ceramics. J. Asian Ceram. Soc. 2021, 9, 281–288.
  231. Biesuz, M.; Galotta, A.; Motta, A.; Kermani, M.; Grasso, S.; Vontorová, J.; Tyrpekl, V.; Vilémová, M.; Sglavo, V.M. Speedy bioceramics: Rapid densification of tricalcium phosphate by ultrafast high-temperature sintering. Mater. Sci. Eng. C 2021, 127, 112246.
  232. Ishihara, S.; Matsumoto, T.; Onoki, T.; Sohmura, T.; Nakahira, A. New concept bioceramics composed of octacalcium phosphate (OCP) and dicarboxylic acid-intercalated OCP via hydrothermal hot-pressing. Mater. Sci. Eng. C 2009, 29, 1885–1888.
  233. Yanagisawa, K.; Kim, J.H.; Sakata, C.; Onda, A.; Sasabe, E.; Yamamoto, T.; Matamoros-Veloza, Z.; Rendón-Angeles, J.C. Hydrothermal sintering under mild temperature conditions: Preparation of calcium-deficient hydroxyapatite compacts. Z. Naturforsch. B 2010, 65, 1038–1044.
  234. Kim, Y.; Kim, S.R.; Song, H.; Yoon, H. Preparation of porous hydroxyapatite/TCP composite block using a hydrothermal hot pressing method. Mater. Sci. Forum 2005, 486–487, 117–120.
  235. Li, J.G.; Hashida, T. In situ formation of hydroxyapatite-whisker ceramics by hydrothermal hot-pressing method. J. Am. Ceram. Soc. 2006, 89, 3544–3546.
  236. Li, J.G.; Hashida, T. Preparation of hydroxyapatite ceramics by hydrothermal hot-pressing method at 300 °C. J. Mater. Sci. 2007, 42, 5013–5019.
  237. Petrakova, N.V.; Lysenkov, A.S.; Ashmarin, A.A.; Egorov, A.A.; Fedotov, A.Y.; Shvorneva, L.I.; Komlev, V.S.; Barinov, S.M. Effect of hot pressing temperature on the microstructure and strength of hydroxyapatite ceramic. Inorg. Mater. Appl. Res. 2013, 4, 362–367.
  238. Hosoi, K.; Hashida, T.; Takahashi, H.; Yamasaki, N.; Korenaga, T. New processing technique for hydroxyapatite ceramics by the hydrothermal hot-pressing method. J. Am. Ceram. Soc. 1996, 79, 2771–2774.
  239. Champion, E. Sintering of calcium phosphate bioceramics. Acta Biomater. 2013, 9, 5855–5875.
  240. Indurkar, A.; Choudhary, R.; Rubenis, K.; Locs, J. Advances in sintering techniques for calcium phosphates ceramics. Materials 2021, 14, 6133.
  241. Evans, J.R.G. Seventy ways to make ceramics. J. Eur. Ceram. Soc. 2008, 28, 1421–1432.
  242. Hench, L.L.; Polak, J.M. Third-generation biomedical materials. Science 2002, 295, 1014–1017.
  243. Black, J. Biological Performance of Materials: Fundamentals of Biocompatibility, 4th ed.; CRC Press: Boca Raton, FL, USA, 2005; p. 520.
  244. Carter, C.B.; Norton, M.G. Ceramic Materials: Science and Engineering, 2nd ed.; Springer: New York, NY, USA, 2013; p. 766.
  245. Benaqqa, C.; Chevalier, J.; Saädaoui, M.; Fantozzi, G. Slow crack growth behaviour of hydroxyapatite ceramics. Biomaterials 2005, 26, 6106–6112.
  246. Pecqueux, F.; Tancret, F.; Payraudeau, N.; Bouler, J.M. Influence of microporosity and macroporosity on the mechanical properties of biphasic calcium phosphate bioceramics: Modelling and experiment. J. Eur. Ceram. Soc. 2010, 30, 819–829.
  247. Hench, L.L. Bioceramics: From concept to clinic. J. Am. Ceram. Soc. 1991, 74, 1487–1510.
  248. Hench, L.L.; Day, D.E.; Höland, W.; Rheinberger, V.M. Glass and medicine. Int. J. Appl. Glass Sci. 2010, 1, 104–117.
  249. Pinchuk, N.D.; Ivanchenko, L.A. Making calcium phosphate biomaterials. Powder Metall. Metal Ceram. 2003, 42, 357–371.
  250. Heimann, R.B. Materials science of crystalline bioceramics: A review of basic properties and applications. CMU J. 2002, 1, 23–46.
  251. Ramesh, S.; Tan, C.Y.; Sopyan, I.; Hamdi, M.; Teng, W.D. Consolidation of nanocrystalline hydroxyapatite powder. Sci. Technol. Adv. Mater. 2007, 8, 124–130.
  252. Wagoner Johnson, A.J.; Herschler, B.A. A review of the mechanical behavior of CaP and CaP/polymer composites for applications in bone replacement and repair. Acta Biomater. 2011, 7, 16–30.
  253. Halouani, R.; Bernache-Assolant, D.; Champion, E.; Ababou, A. Microstructure and related mechanical properties of hot pressed hydroxyapatite ceramics. J. Mater. Sci. Mater. Med. 1994, 5, 563–568.
  254. Suchanek, W.L.; Yoshimura, M. Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants. J. Mater. Res. 1998, 13, 94–117.
  255. Fan, X.; Case, E.D.; Ren, F.; Shu, Y.; Baumann, M.J. Part I: Porosity dependence of the Weibull modulus for hydroxyapatite and other brittle materials. J. Mech. Behav. Biomed. Mater. 2012, 8, 21–36.
  256. Fan, X.; Case, E.D.; Gheorghita, I.; Baumann, M.J. Weibull modulus and fracture strength of highly porous hydroxyapatite. J. Mech. Behav. Biomed. Mater. 2013, 20, 283–295.
  257. Cordell, J.; Vogl, M.; Johnson, A. The influence of micropore size on the mechanical properties of bulk hydroxyapatite and hydroxyapatite scaffolds. J. Mech. Behav. Biomed. Mater. 2009, 2, 560–570.
  258. Suzuki, S.; Sakamura, M.; Ichiyanagi, M.; Ozawa, M. Internal friction of hydroxyapatite and fluorapatite. Ceram. Int. 2004, 30, 625–627.
  259. Suzuki, S.; Takahiro, K.; Ozawa, M. Internal friction and dynamic modulus of polycrystalline ceramics prepared from stoichiometric and Ca-deficient hydroxyapatites. Mater. Sci. Eng. B 1998, 55, 68–70.
  260. Bouler, J.M.; Trecant, M.; Delecrin, J.; Royer, J.; Passuti, N.; Daculsi, G. Macroporous biphasic calcium phosphate ceramics: Influence of five synthesis parameters on compressive strength. J. Biomed. Mater. Res. 1996, 32, 603–609.
  261. Tancret, F.; Bouler, J.M.; Chamousset, J.; Minois, L.M. Modelling the mechanical properties of microporous and macroporous biphasic calcium phosphate bioceramics. J. Eur. Ceram. Soc. 2006, 26, 3647–3656.
  262. Le Huec, J.C.; Schaeverbeke, T.; Clement, D.; Faber, J.; le Rebeller, A. Influence of porosity on the mechanical resistance of hydroxyapatite ceramics under compressive stress. Biomaterials 1995, 16, 113–118.
  263. Hsu, Y.H.; Turner, I.G.; Miles, A.W. Mechanical properties of three different compositions of calcium phosphate bioceramic following immersion in Ringer’s solution and distilled water. J. Mater. Sci. Mater. Med. 2009, 20, 2367–2374.
  264. Torgalkar, A.M. Resonance frequency technique to determine elastic modulus of hydroxyapatite. J. Biomed. Mater. Res. 1979, 13, 907–920.
  265. Gilmore, R.S.; Katz, J.L. Elastic properties of apatites. J. Mater. Sci. 1982, 17, 1131–1141.
  266. Fan, X.; Case, E.D.; Ren, F.; Shu, Y.; Baumann, M.J. Part II: Fracture strength and elastic modulus as a function of porosity for hydroxyapatite and other brittle materials. J. Mech. Behav. Biomed. Mater. 2012, 8, 99–110.
  267. Garcia-Prieto, A.; Hornez, J.C.; Leriche, A.; Pena, P.; Baudín, C. Influence of porosity on the mechanical behaviour of single phase β-TCP ceramics. Ceram. Int. 2017, 43, 6048–6053.
  268. De Aza, P.N.; de Aza, A.H.; de Aza, S. Crystalline bioceramic materials. Bol. Soc. Esp. Ceram. V 2005, 44, 135–145.
  269. Fritsch, A.; Dormieux, L.; Hellmich, C.; Sanahuja, J. Mechanical behavior of hydroxyapatite biomaterials: An experimentally validated micromechanical model for elasticity and strength. J. Biomed. Mater. Res. A 2009, 88A, 149–161.
  270. Ching, W.Y.; Rulis, P.; Misra, A. Ab initio elastic properties and tensile strength of crystalline hydroxyapatite. Acta Biomater. 2009, 5, 3067–3075.
  271. Fritsch, A.; Hellmich, C.; Dormieux, L. The role of disc-type crystal shape for micromechanical predictions of elasticity and strength of hydroxyapatite biomaterials. Philos. Trans. R. Soc. Lond. A 2010, 368, 1913–1935.
  272. Menéndez-Proupin, E.; Cervantes-Rodríguez, S.; Osorio-Pulgar, R.; Franco-Cisterna, M.; Camacho-Montes, H.; Fuentes, M.E. Computer simulation of elastic constants of hydroxyapatite and fluorapatite. J. Mech. Behav. Biomed. Mater. 2011, 4, 1011–1120.
  273. Sun, J.P.; Song, Y.; Wen, G.W.; Wang, Y.; Yang, R. Softening of hydroxyapatite by vacancies: A first principles investigation. Mater. Sci. Eng. C 2013, 33, 1109–1115.
  274. Sha, M.C.; Li, Z.; Bradt, R.C. Single-crystal elastic constants of fluorapatite, Ca5F(PO4)3. J. Appl. Phys. 1994, 75, 7784–7787.
  275. Yoshida, H.; Kim, B.N.; Son, H.W.; Han, Y.H.; Kim, S. Superplastic deformation of transparent hydroxyapatite. Scripta Mater. 2013, 69, 155–158.
  276. Wakai, F.; Kodama, Y.; Sakaguchi, S.; Nonami, T. Superplasticity of hot isostatically pressed hydroxyapatite. J. Am. Ceram. Soc. 1990, 73, 457–460.
  277. Tago, K.; Itatani, K.; Suzuki, T.S.; Sakka, Y.; Koda, S. Densification and superplasticity of hydroxyapatite ceramics. J. Ceram. Soc. Jpn. 2005, 113, 669–673.
  278. Burger, E.L.; Patel, V. Calcium phosphates as bone graft extenders. Orthopedics 2007, 30, 939–942.
  279. Guillaume, B. Filling bone defects with β-TCP in maxillofacial surgery: A review.|Comblement osseux par β-TCP en chirurgie maxillofaciale: Revue des indications. Morphologie 2017, 101, 113–119.
  280. Song, J.; Liu, Y.; Zhang, Y.; Jiao, L. Mechanical properties of hydroxyapatite ceramics sintered from powders with different morphologies. Mater. Sci. Eng. A 2011, 528, 5421–5427.
  281. Dorozhkin, S.V. Calcium orthophosphate-containing biocomposites and hybrid biomaterials for biomedical applications. J. Funct. Biomater. 2015, 6, 708–832.
  282. Bouslama, N.; Ben Ayed, F.; Bouaziz, J. Sintering and mechanical properties of tricalcium phosphate–fluorapatite composites. Ceram. Int. 2009, 35, 1909–1917.
  283. Suchanek, W.; Yashima, M.; Kakihana, M.; Yoshimura, M. Processing and mechanical properties of hydroxyapatite reinforced with hydroxyapatite whiskers. Biomaterials 1996, 17, 1715–1723.
  284. Suchanek, W.; Yashima, M.; Kakihana, M.; Yoshimura, M. Hydroxyapatite/hydroxyapatite-whisker composites without sintering additives: Mechanical properties and microstructural evolution. J. Am. Ceram. Soc. 1997, 80, 2805–2813.
  285. Simsek, D.; Ciftcioglu, R.; Guden, M.; Ciftcioglu, M.; Harsa, S. Mechanical properties of hydroxyapatite composites reinforced with hydroxyapatite whiskers. Key Eng. Mater. 2004, 264–268, 1985–1988.
  286. Bose, S.; Banerjee, A.; Dasgupta, S.; Bandyopadhyay, A. Synthesis, processing, mechanical, and biological property characterization of hydroxyapatite whisker-reinforced hydroxyapatite composites. J. Am. Ceram. Soc. 2009, 92, 323–330.
  287. Lie-Feng, L.; Xiao-Yi, H.; Cai, Y.X.; Weng, J. Reinforcing of porous hydroxyapatite ceramics with hydroxyapatite fibres for enhanced bone tissue engineering. J. Biomim. Biomater. Tissue Eng. 2011, 1314, 67–73.
  288. Shiota, T.; Shibata, M.; Yasuda, K.; Matsuo, Y. Influence of β-tricalcium phosphate dispersion on mechanical properties of hydroxyapatite ceramics. J. Ceram. Soc. Jpn. 2009, 116, 1002–1005.
  289. Shuai, C.; Feng, P.; Nie, Y.; Hu, H.; Liu, J.; Peng, S. Nano-hydroxyapatite improves the properties of β-tricalcium phosphate bone scaffolds. Int. J. Appl. Ceram. Technol. 2013, 10, 1003–1013.
  290. Dorozhkin, S.V.; Ajaal, T. Toughening of porous bioceramic scaffolds by bioresorbable polymeric coatings. Proc. Inst. Mech. Eng. H 2009, 223, 459–470.
  291. Dorozhkin, S.V.; Ajaal, T. Strengthening of dense bioceramic samples using bioresorbable polymers–a statistical approach. J. Biomim. Biomater. Tissue Eng. 2009, 4, 27–39.
  292. Dressler, M.; Dombrowski, F.; Simon, U.; Börnstein, J.; Hodoroaba, V.D.; Feigl, M.; Grunow, S.; Gildenhaar, R.; Neumann, M. Influence of gelatin coatings on compressive strength of porous hydroxyapatite ceramics. J. Eur. Ceram. Soc. 2011, 31, 523–529.
  293. Martinez-Vazquez, F.J.; Perera, F.H.; Miranda, P.; Pajares, A.; Guiberteau, F. Improving the compressive strength of bioceramic robocast scaffolds by polymer infiltration. Acta Biomater. 2010, 6, 4361–4368.
  294. Fedotov, A.Y.; Bakunova, N.V.; Komlev, V.S.; Barinov, S.M. High-porous calcium phosphate bioceramics reinforced by chitosan infiltration. Dokl. Chem. 2011, 439, 233–236.
  295. Martínez-Vázquez, F.J.; Pajares, A.; Guiberteau, F.; Miranda, P. Effect of polymer infiltration on the flexural behavior of β-tricalcium phosphate robocast scaffolds. Materials 2014, 7, 4001–4018.
  296. He, L.H.; Standard, O.C.; Huang, T.T.; Latella, B.A.; Swain, M.V. Mechanical behaviour of porous hydroxyapatite. Acta Biomater. 2008, 4, 577–586.
  297. Yamashita, K.; Owada, H.; Umegaki, T.; Kanazawa, T.; Futagamu, T. Ionic conduction in apatite solid solutions. Solid State Ionics 1988, 28–30, 660–663.
  298. Nagai, M.; Nishino, T. Surface conduction of porous hydroxyapatite ceramics at elevated temperatures. Solid State Ionics 1988, 28–30, 1456–1461.
  299. Valdes, J.J.P.; Rodriguez, A.V.; Carrio, J.G. Dielectric properties and structure of hydroxyapatite ceramics sintered by different conditions. J. Mater. Res. 1995, 10, 2174–2177.
  300. Fanovich, M.A.; Castro, M.S.; Lopez, J.M.P. Analysis of the microstructural evolution in hydroxyapatite ceramics by electrical characterisation. Ceram. Int. 1999, 25, 517–522.
  301. Bensaoud, A.; Bouhaouss, A.; Ferhat, M. Electrical properties in compressed poorly crystalline apatite. J. Solid State Electrochem. 2001, 5, 362–365.
  302. Mahabole, M.P.; Aiyer, R.C.; Ramakrishna, C.V.; Sreedhar, B.; Khairnar, R.S. Synthesis, characterization and gas sensing property of hydroxyapatite ceramic. Bull. Mater. Sci. 2005, 28, 535–545.
  303. Tanaka, Y.; Takata, S.; Shimoe, K.; Nakamura, M.; Nagai, A.; Toyama, T.; Yamashita, K. Conduction properties of non-stoichiometric hydroxyapatite whiskers for biomedical use. J. Ceram. Soc. Jpn. 2008, 116, 815–821.
  304. Tanaka, Y.; Nakamura, M.; Nagai, A.; Toyama, T.; Yamashita, K. Ionic conduction mechanism in Ca-deficient hydroxyapatite whiskers. Mater. Sci. Eng. B 2009, 161, 115–119.
  305. Wang, W.; Itoh, S.; Yamamoto, N.; Okawa, A.; Nagai, A.; Yamashita, K. Electrical polarization of β-tricalcium phosphate ceramics. J. Am. Ceram. Soc. 2010, 93, 2175–2177.
  306. Mahabole, M.P.; Mene, R.U.; Khairnar, R.S. Gas sensing and dielectric studies on cobalt doped hydroxyapatite thick films. Adv. Mater. Lett. 2013, 4, 46–52.
  307. Suresh, M.B.; Biswas, P.; Mahender, V.; Johnson, R. Comparative evaluation of electrical conductivity of hydroxyapatite ceramics densified through ramp and hold, spark plasma and post sinter hot isostatic pressing routes. Mater. Sci. Eng. C 2017, 70, 364–370.
  308. Das, A.; Pamu, D. A comprehensive review on electrical properties of hydroxyapatite based ceramic composites. Mater. Sci. Eng. C 2019, 101, 539–563.
  309. Prezas, P.R.; Dekhtyar, Y.; Sorokins, H.; Costa, M.M.; Soares, M.J.; Graça, M.P.F. Electrical charging of bioceramics by corona discharge. J. Electrost. 2022, 115, 103664.
  310. Gandhi, A.A.; Wojtas, M.; Lang, S.B.; Kholkin, A.L.; Tofail, S.A.M. Piezoelectricity in poled hydroxyapatite ceramics. J. Am. Ceram. Soc. 2014, 97, 2867–2872.
  311. Bystrov, V.S. Piezoelectricity in the ordered monoclinic hydroxyapatite. Ferroelectrics 2015, 475, 148–153.
  312. Horiuchi, N.; Madokoro, K.; Nozaki, K.; Nakamura, M.; Katayama, K.; Nagai, A.; Yamashita, K. Electrical conductivity of polycrystalline hydroxyapatite and its application to electret formation. Solid State Ion. 2018, 315, 19–25.
  313. Saxena, A.; Pandey, M.; Dubey, A.K. Induced electroactive response of hydroxyapatite: A review. J. Indian I. Sci. 2019, 99, 339–359.
  314. Available online: (accessed on 24 June 2022).
  315. Nakamura, S.; Takeda, H.; Yamashita, K. Proton transport polarization and depolarization of hydroxyapatite ceramics. J. Appl. Phys. 2001, 89, 5386–5392.
  316. Gittings, J.P.; Bowen, C.R.; Turner, I.G.; Baxter, F.R.; Chaudhuri, J.B. Polarisation behaviour of calcium phosphate based ceramics. Mater. Sci. Forum. 2008, 587–588, 91–95.
  317. Rivas, M.; del Valle, L.J.; Armelin, E.; Bertran, O.; Turon, P.; Puiggalí, J.; Alemán, C. Hydroxyapatite with permanent electrical polarization: Preparation, characterization, and response against inorganic adsorbates. ChemPhysChem 2018, 19, 1746–1755.
  318. Itoh, S.; Nakamura, S.; Kobayashi, T.; Shinomiya, K.; Yamashita, K.; Itoh, S. Effect of electrical polarization of hydroxyapatite ceramics on new bone formation. Calcif. Tissue Int. 2006, 78, 133–142.
  319. Iwasaki, T.; Tanaka, Y.; Nakamura, M.; Nagai, A.; Hashimoto, K.; Toda, Y.; Katayama, K.; Yamashita, K. Rate of bonelike apatite formation accelerated on polarized porous hydroxyapatite. J. Am. Ceram. Soc. 2008, 91, 3943–3949.
  320. Itoh, S.; Nakamura, S.; Kobayashi, T.; Shinomiya, K.; Yamashita, K. Enhanced bone ingrowth into hydroxyapatite with interconnected pores by electrical polarization. Biomaterials 2006, 27, 5572–5579.
  321. Kobayashi, T.; Itoh, S.; Nakamura, S.; Nakamura, M.; Shinomiya, K.; Yamashita, K. Enhanced bone bonding of hydroxyapatite-coated titanium implants by electrical polarization. J. Biomed. Mater. Res. A 2007, 82A, 145–151.
  322. Bodhak, S.; Bose, S.; Bandyopadhyay, A. Role of surface charge and wettability on early stage mineralization and bone cell-materials interactions of polarized hydroxyapatite. Acta Biomater. 2009, 5, 2178–2188.
  323. Sagawa, H.; Itoh, S.; Wang, W.; Yamashita, K. Enhanced bone bonding of the hydroxyapatite/β-tricalcium phosphate composite by electrical polarization in rabbit long bone. Artif. Organs 2010, 34, 491–497.
  324. Ohba, S.; Wang, W.; Itoh, S.; Nagai, A.; Yamashita, K. Enhanced effects of new bone formation by an electrically polarized hydroxyapatite microgranule/platelet-rich plasma composite gel. Key Eng. Mater. 2013, 529–530, 82–87.
  325. Yamashita, K.; Oikawa, N.; Umegaki, T. Acceleration and deceleration of bone-like crystal growth on ceramic hydroxyapatite by electric poling. Chem. Mater. 1996, 8, 2697–2700.
  326. Teng, N.C.; Nakamura, S.; Takagi, Y.; Yamashita, Y.; Ohgaki, M.; Yamashita, K. A new approach to enhancement of bone formation by electrically polarized hydroxyapatite. J. Dent. Res. 2001, 80, 1925–1929.
  327. Kobayashi, T.; Nakamura, S.; Yamashita, K. Enhanced osteobonding by negative surface charges of electrically polarized hydroxyapatite. J. Biomed. Mater. Res. 2001, 57, 477–484.
  328. Kato, R.; Nakamura, S.; Katayama, K.; Yamashita, K. Electrical polarization of plasma-spray-hydroxyapatite coatings for improvement of osteoconduction of implants. J. Biomed. Mater. Res. A 2005, 74A, 652–658.
  329. Nakamura, S.; Kobayashi, T.; Nakamura, M.; Itoh, S.; Yamashita, K. Electrostatic surface charge acceleration of bone ingrowth of porous hydroxyapatite/β-tricalcium phosphate ceramics. J. Biomed. Mater. Res. A 2010, 92A, 267–275.
  330. Tarafder, S.; Bodhak, S.; Bandyopadhyay, A.; Bose, S. Effect of electrical polarization and composition of biphasic calcium phosphates on early stage osteoblast interactions. J. Biomed. Mater. Res. B Appl. Biomater. 2011, 97B, 306–314.
  331. Ohba, S.; Wang, W.; Itoh, S.; Takagi, Y.; Nagai, A.; Yamashita, K. Acceleration of new bone formation by an electrically polarized hydroxyapatite microgranule/platelet-rich plasma composite. Acta Biomater. 2012, 8, 2778–2787.
  332. Tarafder, S.; Banerjee, S.; Bandyopadhyay, A.; Bose, S. Electrically polarized biphasic calcium phosphates: Adsorption and release of bovine serum albumin. Langmuir 2010, 26, 16625–16629.
  333. Itoh, S.; Nakamura, S.; Nakamura, M.; Shinomiya, K.; Yamashita, K. Enhanced bone regeneration by electrical polarization of hydroxyapatite. Artif. Organs 2006, 30, 863–869.
  334. Nakamura, M.; Nagai, A.; Ohashi, N.; Tanaka, Y.; Sekilima, Y.; Nakamura, S. Regulation of osteoblast-like cell behaviors on hydroxyapatite by electrical polarization. Key Eng. Mater. 2008, 361–363, 1055–1058.
  335. Nakamura, M.; Nagai, A.; Tanaka, Y.; Sekilima, Y.; Yamashita, K. Polarized hydroxyapatite promotes spread and motility of osteoblastic cells. J. Biomed. Mater. Res. A 2010, 92A, 783–790.
  336. Nakamura, M.; Nagai, A.; Yamashita, K. Surface electric fields of apatite electret promote osteoblastic responses. Key Eng. Mater. 2013, 529–530, 357–360.
  337. Nakamura, S.; Kobayashi, T.; Yamashita, K. Extended bioactivity in the proximity of hydroxyapatite ceramic surfaces induced by polarization charges. J. Biomed. Mater. Res. 2002, 61, 593–599.
  338. Wang, W.; Itoh, S.; Tanaka, Y.; Nagai, A.; Yamashita, K. Comparison of enhancement of bone ingrowth into hydroxyapatite ceramics with highly and poorly interconnected pores by electrical polarization. Acta Biomater. 2009, 5, 3132–3140.
  339. Cartmell, S.H.; Thurstan, S.; Gittings, J.P.; Griffiths, S.; Bowen, C.R.; Turner, I.G. Polarization of porous hydroxyapatite scaffolds: Influence on osteoblast cell proliferation and extracellular matrix production. J. Biomed. Mater. Res. A 2014, 102A, 1047–1052.
  340. Nakamura, M.; Kobayashi, A.; Nozaki, K.; Horiuchi, N.; Nagai, A.; Yamashita, K. Improvement of osteoblast adhesion through polarization of plasma-sprayed hydroxyapatite coatings on metal. J. Med. Biol. Eng. 2014, 34, 44–48.
  341. Nagai, A.; Tanaka, K.; Tanaka, Y.; Nakamura, M.; Hashimoto, K.; Yamashita, K. Electric polarization and mechanism of B-type carbonated apatite ceramics. J. Biomed. Mater. Res. A 2011, 99A, 116–124.
  342. Nakamura, M.; Niwa, K.; Nakamura, S.; Sekijima, Y.; Yamashita, K. Interaction of a blood coagulation factor on electrically polarized hydroxyapatite surfaces. J. Biomed. Mater. Res. B Appl. Biomater. 2007, 82B, 29–36.
  343. Ioku, K. Tailored bioceramics of calcium phosphates for regenerative medicine. J. Ceram. Soc. Jpn. 2010, 118, 775–783.
  344. Kawagoe, D.; Ioku, K.; Fujimori, H.; Goto, S. Transparent β-tricalcium phosphate ceramics prepared by spark plasma sintering. J. Ceram. Soc. Jpn. 2004, 112, 462–463.
  345. Chesnaud, A.; Bogicevic, C.; Karolak, F.; Estournès, C.; Dezanneau, G. Preparation of transparent oxyapatite ceramics by combined use of freeze-drying and spark-plasma sintering. Chem. Comm. 2007, 1550–1552.
  346. Eriksson, M.; Liu, Y.; Hu, J.; Gao, L.; Nygren, M.; Shen, Z. Transparent hydroxyapatite ceramics with nanograin structure prepared by high pressure spark plasma sintering at the minimized sintering temperature. J. Eur. Ceram. Soc. 2011, 31, 1533–1540.
  347. Kim, B.N.; Prajatelistia, E.; Han, Y.H.; Son, H.W.; Sakka, Y.; Kim, S. Transparent hydroxyapatite ceramics consolidated by spark plasma sintering. Scripta Mater. 2013, 69, 366–369.
  348. Yun, J.; Son, H.; Prajatelistia, E.; Han, Y.H.; Kim, S.; Kim, B.N. Characterisation of transparent hydroxyapatite nanoceramics prepared by spark plasma sintering. Adv. Appl. Ceram. 2014, 113, 67–72.
  349. Li, Z.; Khor, K.A. Transparent hydroxyapatite obtained through spark plasma sintering: Optical and mechanical properties. Key Eng. Mater. 2015, 631, 51–56.
  350. Fang, Y.; Agrawal, D.K.; Roy, D.M.; Roy, R. Fabrication of transparent hydroxyapatite ceramics by ambient-pressure sintering. Mater. Lett. 1995, 23, 147–151.
  351. Varma, H.; Vijayan, S.P.; Babu, S.S. Transparent hydroxyapatite ceramics through gel-casting and low-temperature sintering. J. Am. Ceram. Soc. 2002, 85, 493–495.
  352. Watanabe, Y.; Ikoma, T.; Monkawa, A.; Suetsugu, Y.; Yamada, H.; Tanaka, J.; Moriyoshi, Y. Fabrication of transparent hydroxyapatite sintered body with high crystal orientation by pulse electric current sintering. J. Am. Ceram. Soc. 2005, 88, 243–245.
  353. Kotobuki, N.; Ioku, K.; Kawagoe, D.; Fujimori, H.; Goto, S.; Ohgushi, H. Observation of osteogenic differentiation cascade of living mesenchymal stem cells on transparent hydroxyapatite ceramics. Biomaterials 2005, 26, 779–785.
  354. John, A.; Varma, H.K.; Vijayan, S.; Bernhardt, A.; Lode, A.; Vogel, A.; Burmeister, B.; Hanke, T.; Domaschke, H.; Gelinsky, M. in vitro investigations of bone remodeling on a transparent hydroxyapatite ceramic. Biomed. Mater. 2009, 4, 015007.
  355. Wang, J.; Shaw, L.L. Transparent nanocrystalline hydroxyapatite by pressure-assisted sintering. Scripta Mater. 2010, 63, 593–596.
  356. Boilet, L.; Descamps, M.; Rguiti, E.; Tricoteaux, A.; Lu, J.; Petit, F.; Lardot, V.; Cambier, F.; Leriche, A. Processing and properties of transparent hydroxyapatite and β tricalcium phosphate obtained by HIP process. Ceram. Int. 2013, 39, 283–288.
  357. Han, Y.H.; Kim, B.N.; Yoshida, H.; Yun, J.; Son, H.W.; Lee, J.; Kim, S. Spark plasma sintered superplastic deformed transparent ultrafine hydroxyapatite nanoceramics. Adv. Appl. Ceram. 2016, 115, 174–184.
  358. Nakamura, T.; Fukuhara, T.; Izui, H. Mechanical properties of hydroxyapatites sintered by spark plasma sintering. Ceram. Trans. 2006, 194, 265–272.
  359. Grossin, D.; Rollin-Martinet, S.; Estournès, C.; Rossignol, F.; Champion, E.; Combes, C.; Rey, C.; Geoffroy, C.; Drouet, C. Biomimetic apatite sintered at very low temperature by spark plasma sintering: Physico-chemistry and microstructure aspects. Acta Biomater. 2010, 6, 577–585.
  360. Ortali, C.; Julien, I.; Vandenhende, M.; Drouet, C.; Champion, E. Consolidation of bone-like apatite bioceramics by spark plasma sintering of amorphous carbonated calcium phosphate at very low temperature. J. Eur. Ceram. Soc. 2018, 38, 2098–2109.
  361. Kobune, M.; Mineshige, A.; Fujii, S.; Iida, H. Preparation of translucent hydroxyapatite ceramics by HIP and their physical properties. J. Ceram. Soc. Jpn. 1997, 105, 210–213.
  362. Barralet, J.E.; Fleming, G.J.P.; Campion, C.; Harris, J.J.; Wright, A.J. Formation of translucent hydroxyapatite ceramics by sintering in carbon dioxide atmospheres. J. Mater. Sci. 2003, 38, 3979–3993.
  363. Chaudhry, A.A.; Yan, H.; Gong, K.; Inam, F.; Viola, G.; Reece, M.J.; Goodall, J.B.M.; ur Rehman, I.; McNeil-Watson, F.K.; Corbett, J.C.W.; et al. High-strength nanograined and translucent hydroxyapatite monoliths via continuous hydrothermal synthesis and optimized spark plasma sintering. Acta Biomater. 2011, 7, 791–799.
  364. Tancred, D.C.; McCormack, B.A.; Carr, A.J. A synthetic bone implant macroscopically identical to cancellous bone. Biomaterials 1998, 19, 2303–2311.
  365. Miao, X.; Sun, D. Graded/gradient porous biomaterials. Materials 2010, 3, 26–47.
  366. Schliephake, H.; Neukam, F.W.; Klosa, D. Influence of pore dimensions on bone ingrowth into porous hydroxylapatite blocks used as bone graft substitutes. A histometric study. Int. J. Oral Maxillofac. Surg. 1991, 20, 53–58.
  367. Otsuki, B.; Takemoto, M.; Fujibayashi, S.; Neo, M.; Kokubo, T.; Nakamura, T. Pore throat size and connectivity determine bone and tissue ingrowth into porous implants: Three-dimensional micro-CT based structural analyses of porous bioactive titanium implants. Biomaterials 2006, 27, 5892–5900.
  368. Hing, K.A.; Best, S.M.; Bonfield, W. Characterization of porous hydroxyapatite. J. Mater. Sci. Mater. Med. 1999, 10, 135–145.
  369. Lu, J.X.; Flautre, B.; Anselme, K.; Hardouin, P.; Gallur, A.; Descamps, M.; Thierry, B. Role of interconnections in porous bioceramics on bone recolonization in vitro and in vivo. J. Mater. Sci. Mater. Med. 1999, 10, 111–120.
  370. Karageorgiou, V.; Kaplan, D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 2005, 26, 5474–5491.
  371. Tamai, N.; Myoui, A.; Kudawara, I.; Ueda, T.; Yoshikawa, H. Novel fully interconnected porous hydroxyapatite ceramic in surgical treatment of benign bone tumor. J. Orthop. Sci. 2010, 15, 560–568.
  372. Panzavolta, S.; Torricelli, P.; Amadori, S.; Parrilli, A.; Rubini, K.; Della Bella, E.; Fini, M.; Bigi, A. 3D interconnected porous biomimetic scaffolds: In vitro cell response. J. Biomed. Mater. Res. A 2013, 101A, 3560–3570.
  373. Jin, L.; Feng, Z.Q.; Wang, T.; Ren, Z.; Ma, S.; Wu, J.; Sun, D. A novel fluffy hydroxylapatite fiber scaffold with deep interconnected pores designed for three-dimensional cell culture. J. Mater. Chem. B 2014, 2, 129–136.
  374. Flautre, B.; Descamps, M.; Delecourt, C.; Blary, M.C.; Hardouin, P. Porous HA ceramic for bone replacement: Role of the pores and interconnections–experimental study in the rabbits. J. Mater. Sci. Mater. Med. 2001, 12, 679–682.
  375. Mastrogiacomo, M.; Scaglione, S.; Martinetti, R.; Dolcini, L.; Beltrame, F.; Cancedda, R.; Quarto, R. Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics. Biomaterials 2006, 27, 3230–3237.
  376. Okamoto, M.; Dohi, Y.; Ohgushi, H.; Shimaoka, H.; Ikeuchi, M.; Matsushima, A.; Yonemasu, K.; Hosoi, H. Influence of the porosity of hydroxyapatite ceramics on in vitro and in vivo bone formation by cultured rat bone marrow stromal cells. J. Mater. Sci. Mater. Med. 2006, 17, 327–336.
  377. Li, X.; Liu, H.; Niu, X.; Fan, Y.; Feng, Q.; Cui, F.Z.; Watari, F. Osteogenic differentiation of human adipose-derived stem cells induced by osteoinductive calcium phosphate ceramics. J. Biomed. Mater. Res. B Appl. Biomater. 2011, 97B, 10–19.
  378. Hong, M.H.; Kim, S.M.; Han, M.H.; Kim, Y.H.; Lee, Y.K.; Oh, D.S. Evaluation of microstructure effect of the porous spherical β-tricalcium phosphate granules on cellular responses. Ceram. Int. 2014, 40, 6095–6102.
  379. De Godoy, R.F.; Hutchens, S.; Campion, C.; Blunn, G. Silicate-substituted calcium phosphate with enhanced strut porosity stimulates osteogenic differentiation of human mesenchymal stem cells. J. Mater. Sci. Mater. Med. 2015, 26, 54.
  380. Omae, H.; Mochizuki, Y.; Yokoya, S.; Adachi, N.; Ochi, M. Effects of interconnecting porous structure of hydroxyapatite ceramics on interface between grafted tendon and ceramics. J. Biomed. Mater. Res. A 2006, 79A, 329–337.
  381. Yoshikawa, H.; Tamai, N.; Murase, T.; Myoui, A. Interconnected porous hydroxyapatite ceramics for bone tissue engineering. J. R. Soc. Interface 2009, 6, S341–S348.
  382. Ribeiro, G.B.M.; Trommer, R.M.; dos Santos, L.A.; Bergmann, C.P. Novel method to produce β-TCP scaffolds. Mater. Lett. 2011, 65, 275–277.
  383. Silva, T.S.N.; Primo, B.T.; Silva, A.N., Jr.; Machado, D.C.; Viezzer, C.; Santos, L.A. Use of calcium phosphate cement scaffolds for bone tissue engineering: In vitro study. Acta Cir. Bras. 2011, 26, 7–11.
  384. De Moraes MacHado, J.L.; Giehl, I.C.; Nardi, N.B.; dos Santos, L.A. Evaluation of scaffolds based on α-tricalcium phosphate cements for tissue engineering applications. IEEE Trans. Biomed. Eng. 2011, 58, 1814–1819.
  385. Li, S.H.; de Wijn, J.R.; Layrolle, P.; de Groot, K. Novel method to manufacture porous hydroxyapatite by dual-phase mixing. J. Am. Ceram. Soc. 2003, 86, 65–72.
  386. De Oliveira, J.F.; de Aguiar, P.F.; Rossi, A.M.; Soares, G.D.A. Effect of process parameters on the characteristics of porous calcium phosphate ceramics for bone tissue scaffolds. Artif. Organs 2003, 27, 406–411.
  387. Swain, S.K.; Bhattacharyya, S. Preparation of high strength macroporous hydroxyapatite scaffold. Mater. Sci. Eng. C 2013, 33, 67–71.
  388. Maeda, H.; Kasuga, T.; Nogami, M.; Kagami, H.; Hata, K.; Ueda, M. Preparation of bonelike apatite composite sponge. Key Eng. Mater. 2004, 254–256, 497–500.
  389. Le Ray, A.M.; Gautier, H.; Bouler, J.M.; Weiss, P.; Merle, C. A new technological procedure using sucrose as porogen compound to manufacture porous biphasic calcium phosphate ceramics of appropriate micro- and macrostructure. Ceram. Int. 2010, 36, 93–101.
  390. Li, S.H.; de Wijn, J.R.; Layrolle, P.; de Groot, K. Synthesis of macroporous hydroxyapatite scaffolds for bone tissue engineering. J. Biomed. Mater. Res. 2002, 61, 109–120.
  391. Hesaraki, S.; Sharifi, D. Investigation of an effervescent additive as porogenic agent for bone cement macroporosity. Biomed. Mater. Eng. 2007, 17, 29–38.
  392. Hesaraki, S.; Moztarzadeh, F.; Sharifi, D. Formation of interconnected macropores in apatitic calcium phosphate bone cement with the use of an effervescent additive. J. Biomed. Mater. Res. A 2007, 83A, 80–87.
  393. Tas, A.C. Preparation of porous apatite granules from calcium phosphate cement. J. Mater. Sci. Mater. Med. 2008, 19, 2231–2239.
  394. Şahin, E.; Çiftçioğlu, M. Compositional, microstructural and mechanical effects of NaCl porogens in brushite cement scaffolds. J. Mech. Behav. Biomed. Mater. 2021, 116, 104363.
  395. Descamps, M.; Duhoo, T.; Monchau, F.; Lu, J.; Hardouin, P.; Hornez, J.C.; Leriche, A. Manufacture of macroporous β-tricalcium phosphate bioceramics. J. Eur. Ceram. Soc. 2008, 28, 149–157.
  396. Yao, X.; Tan, S.; Jiang, D. Improving the properties of porous hydroxyapatite ceramics by fabricating methods. J. Mater. Sci. 2005, 40, 4939–4942.
  397. Song, H.Y.; Youn, M.H.; Kim, Y.H.; Min, Y.K.; Yang, H.M.; Lee, B.T. Fabrication of porous β-TCP bone graft substitutes using PMMA powder and their biocompatibility study. Korean J. Mater. Res. 2007, 17, 318–322.
  398. Indra, A.; Hadi, F.; Mulyadi, I.H.; Affi, J.; Gunawarman. A novel fabrication procedure for producing high strength hydroxyapatite ceramic scaffolds with high porosity. Ceram. Int. 2021, 47, 26991–27001.
  399. Almirall, A.; Larrecq, G.; Delgado, J.A.; Martínez, S.; Planell, J.A.; Ginebra, M.P. Fabrication of low temperature macroporous hydroxyapatite scaffolds by foaming and hydrolysis of an α-TCP paste. Biomaterials 2004, 25, 3671–3680.
  400. Huang, X.; Miao, X. Novel porous hydroxyapatite prepared by combining H2O2 foaming with PU sponge and modified with PLGA and bioactive glass. J. Biomater. Appl. 2007, 21, 351–374.
  401. Li, B.; Chen, X.; Guo, B.; Wang, X.; Fan, H.; Zhang, X. Fabrication and cellular biocompatibility of porous carbonated biphasic calcium phosphate ceramics with a nanostructure. Acta Biomater. 2009, 5, 134–143.
  402. Cheng, Z.; Zhao, K.; Wu, Z.P. Structure control of hydroxyapatite ceramics via an electric field assisted freeze casting method. Ceram. Int. 2015, 41, 8599–8604.
  403. Lyu, Y.; Asoh, T.A.; Uyama, H. Facile synthesis of a three-dimensional hydroxyapatite monolith for protein adsorption. J. Mater. Chem. B 2021, 9, 9711–9719.
  404. Tadic, D.; Beckmann, F.; Schwarz, K.; Epple, M. A novel method to produce hydroxylapatite objects with interconnecting porosity that avoids sintering. Biomaterials 2004, 25, 3335–3340.
  405. Sepulveda, P.; Binner, J.G.; Rogero, S.O.; Higa, O.Z.; Bressiani, J.C. Production of porous hydroxyapatite by the gel-casting of foams and cytotoxic evaluation. J. Biomed. Mater. Res. 2000, 50, 27–34.
  406. Chevalier, E.; Chulia, D.; Pouget, C.; Viana, M. Fabrication of porous substrates: A review of processes using pore forming agents in the biomaterial field. J. Pharm. Sci. 2008, 97, 1135–1154.
  407. Tang, Y.J.; Tang, Y.F.; Lv, C.T.; Zhou, Z.H. Preparation of uniform porous hydroxyapatite biomaterials by a new method. Appl. Surf. Sci. 2008, 254, 5359–5362.
  408. Abdulqader, S.T.; Rahman, I.A.; Ismail, H.; Ponnuraj Kannan, T.; Mahmood, Z. A simple pathway in preparation of controlled porosity of biphasic calcium phosphate scaffold for dentin regeneration. Ceram. Int. 2013, 39, 2375–2381.
  409. Wen, F.H.; Wang, F.; Gai, Y.; Wang, M.T.; Lai, Q.H. Preparation of mesoporous hydroxylapatite ceramics using polystyrene microspheres as template. Appl. Mech. Mater. 2013, 389, 194–198.
  410. Sari, M.; Hening, P.; Chotimah; Ana, I.D.; Yusuf, Y. Bioceramic hydroxyapatite-based scaffold with a porous structure using honeycomb as a natural polymeric porogen for bone tissue engineering. Biomater. Res. 2021, 25, 2.
  411. Castillo-Paz, A.M.; Cañon-Davila, D.F.; Londoño-Restrepo, S.M.; Jimenez-Mendoza, D.; Pfeiffer, H.; Ramírez-Bon, R.; Rodriguez-Garcia, M.E. Fabrication and characterization of bioinspired nanohydroxyapatite scaffolds with different porosities. Ceram. Int. 2022, in press.
  412. Cho, S.; Kim, J.; Lee, S.B.; Choi, M.; Kim, D.H.; Jo, I.; Kwon, H.; Kim, Y. Fabrication of functionally graded hydroxyapatite and structurally graded porous hydroxyapatite by using multi-walled carbon nanotubes. Compos. A 2020, 139, 106138.
  413. Guda, T.; Appleford, M.; Oh, S.; Ong, J.L. A cellular perspective to bioceramic scaffolds for bone tissue engineering: The state of the art. Curr. Top. Med. Chem. 2008, 8, 290–299.
  414. Tian, J.; Tian, J. Preparation of porous hydroxyapatite. J. Mater. Sci. 2001, 36, 3061–3066.
  415. Swain, S.K.; Bhattacharyya, S.; Sarkar, D. Preparation of porous scaffold from hydroxyapatite powders. Mater. Sci. Eng. C 2011, 31, 1240–1244.
  416. Zhao, K.; Tang, Y.F.; Qin, Y.S.; Luo, D.F. Polymer template fabrication of porous hydroxyapatite scaffolds with interconnected spherical pores. J. Eur. Ceram. Soc. 2011, 31, 225–229.
  417. Sung, J.H.; Shin, K.H.; Moon, Y.W.; Koh, Y.H.; Choi, W.Y.; Kim, H.E. Production of porous calcium phosphate (CaP) ceramics with highly elongated pores using carbon-coated polymeric templates. Ceram. Int. 2012, 38, 93–97.
  418. Morejón, L.; Delgado, J.A.; Ribeiro, A.A.; de Oliveira, M.V.; Mendizábal, E.; García, I.; Alfonso, A.; Poh, P.; van Griensven, M.; Balmayor, E.R. Development, characterization and in vitro biological properties of scaffolds fabricated from calcium phosphate nanoparticles. Int. J. Mol. Sci. 2019, 20, 1790.
  419. Deville, S.; Saiz, E.; Tomsia, A.P. Freeze casting of hydroxyapatite scaffolds for bone tissue engineering. Biomaterials 2006, 27, 5480–5489.
  420. Lee, E.J.; Koh, Y.H.; Yoon, B.H.; Kim, H.E.; Kim, H.W. Highly porous hydroxyapatite bioceramics with interconnected pore channels using camphene-based freeze casting. Mater. Lett. 2007, 61, 2270–2273.
  421. Fu, Q.; Rahaman, M.N.; Dogan, F.; Bal, B.S. Freeze casting of porous hydroxyapatite scaffolds. I. Processing and general microstructure. J. Biomed. Mater. Res. B Appl. Biomater. 2008, 86B, 125–135.
  422. Impens, S.; Schelstraete, R.; Luyten, J.; Mullens, S.; Thijs, I.; van Humbeeck, J.; Schrooten, J. Production and characterisation of porous calcium phosphate structures with controllable hydroxyapatite/β-tricalcium phosphate ratios. Adv. Appl. Ceram. 2009, 108, 494–500.
  423. Macchetta, A.; Turner, I.G.; Bowen, C.R. Fabrication of HA/TCP scaffolds with a graded and porous structure using a camphene-based freeze-casting method. Acta Biomater. 2009, 5, 1319–1327.
  424. Potoczek, M.; Zima, A.; Paszkiewicz, Z.; Ślósarczyk, A. Manufacturing of highly porous calcium phosphate bioceramics via gel-casting using agarose. Ceram. Int. 2009, 35, 2249–2254.
  425. Zuo, K.H.; Zeng, Y.P.; Jiang, D. Effect of polyvinyl alcohol additive on the pore structure and morphology of the freeze-cast hydroxyapatite ceramics. Mater. Sci. Eng. C 2010, 30, 283–287.
  426. Soon, Y.M.; Shin, K.H.; Koh, Y.H.; Lee, J.H.; Choi, W.Y.; Kim, H.E. Fabrication and compressive strength of porous hydroxyapatite scaffolds with a functionally graded core/shell structure. J. Eur. Ceram. Soc. 2011, 31, 13–18.
  427. Hesaraki, S. Freeze-casted nanostructured apatite scaffold obtained from low temperature biomineralization of reactive calcium phosphates. Key Eng. Mater. 2014, 587, 21–26.
  428. Ng, S.; Guo, J.; Ma, J.; Loo, S.C.J. Synthesis of high surface area mesostructured calcium phosphate particles. Acta Biomater. 2010, 6, 3772–3781.
  429. Walsh, D.; Hopwood, J.D.; Mann, S. Crystal tectonics: Construction of reticulated calcium phosphate frameworks in bicontinuous reverse microemulsions. Science 1994, 264, 1576–1578.
  430. Walsh, D.; Mann, S. Chemical synthesis of microskeletal calcium phosphate in bicontinuous microemulsions. Chem. Mater. 1996, 8, 1944–1953.
  431. Zhao, K.; Tang, Y.F.; Qin, Y.S.; Wei, J.Q. Porous hydroxyapatite ceramics by ice templating: Freezing characteristics and mechanical properties. Ceram. Int. 2011, 37, 635–639.
  432. Zhou, K.; Zhang, Y.; Zhang, D.; Zhang, X.; Li, Z.; Liu, G.; Button, T.W. Porous hydroxyapatite ceramics fabricated by an ice-templating method. Scripta Mater. 2011, 64, 426–429.
  433. Flauder, S.; Gbureck, U.; Muller, F.A. TCP scaffolds with an interconnected and aligned porosity fabricated via ice-templating. Key Eng. Mater. 2013, 529–530, 129–132.
  434. Zhang, Y.; Zhou, K.; Bao, Y.; Zhang, D. Effects of rheological properties on ice-templated porous hydroxyapatite ceramics. Mater. Sci. Eng. C 2013, 33, 340–346.
  435. Kitamura, M.; Ohtsuki, C.; Ogata, S.; Kamitakahara, M.; Tanihara, M. Microstructure and bioresorbable properties of α-TCP ceramic porous body fabricated by direct casting method. Mater. Trans. 2004, 45, 983–988.
  436. Ioku, K.; Kawachi, G.; Nakahara, K.; Ishida, E.H.; Minagi, H.; Okuda, T.; Yonezawa, I.; Kurosawa, H.; Ikeda, T. Porous granules of β-tricalcium phosphate composed of rod-shaped particles. Key Eng. Mater. 2006, 309–311, 1059–1062.
  437. White, E.; Shors, E.C. Biomaterial aspects of Interpore-200 porous hydroxyapatite. Dent. Clin. North Am. 1986, 30, 49–67.
  438. Aizawa, M.; Howell, S.F.; Itatani, K.; Yokogawa, Y.; Nishizawa, K.; Toriyama, M.; Kameyama, T. Fabrication of porous ceramics with well-controlled open pores by sintering of fibrous hydroxyapatite particles. J. Ceram. Soc. Jpn. 2000, 108, 249–253.
  439. Nakahira, A.; Tamai, M.; Sakamoto, K.; Yamaguchi, S. Sintering and microstructure of porous hydroxyapatite. J. Ceram. Soc. Jpn. 2000, 108, 99–104.
  440. Koh, Y.H.; Kim, H.W.; Kim, H.E.; Halloran, J.W. Fabrication of macrochannelled-hydroxyapatite bioceramic by a coextrusion process. J. Am. Ceram. Soc. 2002, 85, 2578–2580.
  441. Charriere, E.; Lemaitre, J.; Zysset, P. Hydroxyapatite cement scaffolds with controlled macroporosity: Fabrication protocol and mechanical properties. Biomaterials 2003, 24, 809–817.
  442. Gonzalez-McQuire, R.; Green, D.; Walsh, D.; Hall, S.; Chane-Ching, J.Y.; Oreffo, R.O.C.; Mann, S. Fabrication of hydroxyapatite sponges by dextran sulphate/amino acid templating. Biomaterials 2005, 26, 6652–6656.
  443. Eichenseer, C.; Will, J.; Rampf, M.; Wend, S.; Greil, P. Biomorphous porous hydroxyapatite-ceramics from rattan (Calamus Rotang). J. Mater. Sci. Mater. Med. 2010, 21, 131–137.
  444. Walsh, D.; Boanini, E.; Tanaka, J.; Mann, S. Synthesis of tri-calcium phosphate sponges by interfacial deposition and thermal transformation of self-supporting calcium phosphate films. J. Mater. Chem. 2005, 15, 1043–1048.
  445. Song, H.Y.; Islam, S.; Lee, B.T. A novel method to fabricate unidirectional porous hydroxyapatite body using ethanol bubbles in a viscous slurry. J. Am. Ceram. Soc. 2008, 91, 3125–3127.
  446. Zhou, L.; Wang, D.; Huang, W.; Yao, A.; Kamitakahara, M.; Ioku, K. Preparation and characterization of periodic porous frame of hydroxyapatite. J. Ceram. Soc. Jpn. 2009, 117, 521–524.
  447. Xu, S.; Li, D.; Lu, B.; Tang, Y.; Wang, C.; Wang, Z. Fabrication of a calcium phosphate scaffold with a three dimensional channel network and its application to perfusion culture of stem cells. Rapid Prototyp. J. 2007, 13, 99–106.
  448. Saiz, E.; Gremillard, L.; Menendez, G.; Miranda, P.; Gryn, K.; Tomsia, A.P. Preparation of porous hydroxyapatite scaffolds. Mater. Sci. Eng. C 2007, 27, 546–550.
  449. Sakamoto, M.; Nakasu, M.; Matsumoto, T.; Okihana, H. Development of superporous hydroxyapatites and their examination with a culture of primary rat osteoblasts. J. Biomed. Mater. Res. A 2007, 82A, 238–242.
  450. Wang, H.; Zhai, L.; Li, Y.; Shi, T. Preparation of irregular mesoporous hydroxyapatite. Mater. Res. Bull. 2008, 43, 1607–1614.
  451. Sakamoto, M. Development and evaluation of superporous hydroxyapatite ceramics with triple pore structure as bone tissue scaffold. J. Ceram. Soc. Jpn. 2010, 118, 753–757.
  452. Sakamoto, M.; Matsumoto, T. Development and evaluation of superporous ceramics bone tissue scaffold materials with triple pore structure a) hydroxyapatite, b) beta-tricalcium phosphate. In Bone Regeneration; Tal, H., Ed.; InTech Open: Rijeka, Croatia, 2012; pp. 301–320.
  453. Deisinger, U. Generating porous ceramic scaffolds: Processing and properties. Key Eng. Mater. 2010, 441, 155–179.
  454. Ishikawa, K.; Tsuru, K.; Pham, T.K.; Maruta, M.; Matsuya, S. Fully-interconnected pore forming calcium phosphate cement. Key Eng. Mater. 2012, 493–494, 832–835.
  455. Yoon, H.J.; Kim, U.C.; Kim, J.H.; Koh, Y.H.; Choi, W.Y.; Kim, H.E. Fabrication and characterization of highly porous calcium phosphate (CaP) ceramics by freezing foamed aqueous CaP suspensions. J. Ceram. Soc. Jpn. 2011, 119, 573–576.
  456. Ahn, M.K.; Shin, K.H.; Moon, Y.W.; Koh, Y.H.; Choi, W.Y.; Kim, H.E. Highly porous biphasic calcium phosphate (BCP) ceramics with large interconnected pores by freezing vigorously foamed BCP suspensions under reduced pressure. J. Am. Ceram. Soc. 2011, 94, 4154–4156.
  457. Schlosser, M.; Kleebe, H.J. Vapor transport sintering of porous calcium phosphate ceramics. J. Am. Ceram. Soc. 2012, 95, 1581–1587.
  458. Zheng, W.; Liu, G.; Yan, C.; Xiao, Y.; Miao, X.G. Strong and bioactive tri-calcium phosphate scaffolds with tube-like macropores. J. Biomim. Biomater. Tissue Eng. 2014, 19, 65–75.
  459. Tsuru, K.; Nikaido, T.; Munar, M.L.; Maruta, M.; Matsuya, S.; Nakamura, S.; Ishikawa, K. Synthesis of carbonate apatite foam using β-TCP foams as precursors. Key Eng. Mater. 2014, 587, 52–55.
  460. Chen, Z.C.; Zhang, X.L.; Zhou, K.; Cai, H.; Liu, C.Q. Novel fabrication of hierarchically porous hydroxyapatite scaffolds with refined porosity and suitable strength. Adv. Appl. Ceram. 2015, 114, 183–187.
  461. Swain, S.K.; Bhattacharyya, S.; Sarkar, D. Fabrication of porous hydroxyapatite scaffold via polyethylene glycol-polyvinyl alcohol hydrogel state. Mater. Res. Bull. 2015, 64, 257–261.
  462. Charbonnier, B.; Laurent, C.; Marchat, D. Porous hydroxyapatite bioceramics produced by impregnation of 3D-printed wax mold: Slurry feature optimization. J. Eur. Ceram. Soc. 2016, 36, 4269–4279.
  463. Roy, D.M.; Linnehan, S.K. Hydroxyapatite formed from coral skeletal carbonate by hydrothermal exchange. Nature 1974, 247, 220–222.
  464. Zhang, X.; Vecchio, K.S. Conversion of natural marine skeletons as scaffolds for bone tissue engineering. Front. Mater. Sci. 2013, 7, 103–117.
  465. Yang, Y.; Yao, Q.; Pu, X.; Hou, Z.; Zhang, Q. Biphasic calcium phosphate macroporous scaffolds derived from oyster shells for bone tissue engineering. Chem. Eng. J. 2011, 173, 837–845.
  466. Tampieri, A.; Sprio, S.; Ruffini, A.; Celotti, G.; Lesci, I.G.; Roveri, N. From wood to bone: Multi-step process to convert wood hierarchical structures into biomimetic hydroxyapatite scaffolds for bone tissue engineering. J. Mater. Chem. 2009, 19, 4973–4980.
  467. Thanh, T.N.X.; Maruta, M.; Tsuru, K.; Matsuya, S.; Ishikawa, K. Three–dimensional porous carbonate apatite with sufficient mechanical strength as a bone substitute material. Adv. Mater. Res. 2014, 891–892, 1559–1564.
  468. Kasuga, T.; Ota, Y.; Tsuji, K.; Abe, Y. Preparation of high-strength calcium phosphate ceramics with low modulus of elasticity containing β-Ca(PO3)2 fibers. J. Am. Ceram. Soc. 1996, 79, 1821–1824.
  469. Suchanek, W.L.; Yoshimura, M. Preparation of fibrous, porous hydroxyapatite ceramics from hydroxyapatite whiskers. J. Am. Ceram. Soc. 1998, 81, 765–767.
  470. Moroni, L.; de Wijn, J.R.; van Blitterswijk, C.A. Integrating novel technologies to fabricate smart scaffolds. J. Biomater. Sci. Polymer Edn. 2008, 19, 543–572.
  471. Studart, A.R.; Gonzenbach, U.T.; Tervoort, E.; Gauckler, L.J. Processing routes to macroporous ceramics: A review. J. Am. Ceram. Soc. 2006, 89, 1771–1789.
  472. Hing, K.; Annaz, B.; Saeed, S.; Revell, P.; Buckland, T. Microporosity enhances bioactivity of synthetic bone graft substitutes. J. Mater. Sci. Mater. Med. 2005, 16, 467–475.
  473. Wang, Z.; Sakakibara, T.; Sudo, A.; Kasai, Y. Porosity of β-tricalcium phosphate affects the results of lumbar posterolateral fusion. J. Spinal Disord. Tech. 2013, 26, E40–E45.
  474. Lan Levengood, S.K.; Polak, S.J.; Wheeler, M.B.; Maki, A.J.; Clark, S.G.; Jamison, R.D.; Wagoner Johnson, A.J. Multiscale osteointegration as a new paradigm for the design of calcium phosphate scaffolds for bone regeneration. Biomaterials 2010, 31, 3552–3563.
  475. Ruksudjarit, A.; Pengpat, K.; Rujijanagul, G.; Tunkasiri, T. The fabrication of nanoporous hydroxyapatite ceramics. Adv. Mater. Res. 2008; 47–50, 797–800.
  476. Li, Y.; Tjandra, W.; Tam, K.C. Synthesis and characterization of nanoporous hydroxyapatite using cationic surfactants as templates. Mater. Res. Bull. 2008, 43, 2318–2326.
  477. El Asri, S.; Laghzizil, A.; Saoiabi, A.; Alaoui, A.; El Abassi, K.; M’hamdi, R.; Coradin, T. A novel process for the fabrication of nanoporous apatites from Moroccan phosphate rock. Colloid Surf. A 2009, 350, 73–78.
  478. Raksujarit, A.; Pengpat, K.; Rujijanagul, G.; Tunkasiri, T. Processing and properties of nanoporous hydroxyapatite ceramics. Mater. Des. 2010, 31, 1658–1660.
  479. Ramli, R.A.; Adnan, R.; Bakar, M.A.; Masudi, S.M. Synthesis and characterisation of pure nanoporous hydroxyapatite. J. Phys. Sci. 2011, 22, 25–37.
  480. LeGeros, R.Z. Calcium phosphate-based osteoinductive materials. Chem. Rev. 2008, 108, 4742–4753.
  481. Prokopiev, O.; Sevostianov, I. Dependence of the mechanical properties of sintered hydroxyapatite on the sintering temperature. Mater. Sci. Eng. A 2006, 431, 218–227.
  482. Daculsi, G.; Jegoux, F.; Layrolle, P. The micro macroporous biphasic calcium phosphate concept for bone reconstruction and tissue engineering. In Advanced Biomaterials: Fundamentals, Processing and Applications; Basu, B., Katti, D.S., Kumar, A., Eds.; American Ceramic Society: Columbus, OH, USA; Wiley: Hoboken, NJ, USA, 2009; p. 768.
  483. Shipman, P.; Foster, G.; Schoeninger, M. Burnt bones and teeth: An experimental study of color, morphology, crystal structure and shrinkage. J. Archaeol. Sci. 1984, 11, 307–325.
  484. Rice, R.W. Porosity of Ceramics; Marcel Dekker: New York, NY, USA, 1998; p. 560.
  485. Fan, J.; Lei, J.; Yu, C.; Tu, B.; Zhao, D. Hard-templating synthesis of a novel rod-like nanoporous calcium phosphate bioceramics and their capacity as antibiotic carriers. Mater. Chem. Phys. 2007, 103, 489–493.
  486. Hsu, Y.H.; Turner, I.G.; Miles, A.W. Fabrication of porous bioceramics with porosity gradients similar to the bimodal structure of cortical and cancellous bone. J. Mater. Sci. Mater. Med. 2007, 18, 2251–2256.
  487. Munch, E.; Franco, J.; Deville, S.; Hunger, P.; Saiz, E.; Tomsia, A.P. Porous ceramic scaffolds with complex architectures. JOM 2008, 60, 54–59.
  488. Naqshbandi, A.R.; Sopyan, I.; Gunawan. Development of porous calcium phosphate bioceramics for bone implant applications: A review. Rec. Pat. Mater. Sci. 2013, 6, 238–252.
  489. Jodati, H.; Yılmaz, B.; Evis, Z. A review of bioceramic porous scaffolds for hard tissue applications: Effects of structural features. Ceram. Int. 2020, 46, 15725–15739.
  490. Yan, X.; Yu, C.; Zhou, X.; Tang, J.; Zhao, D. Highly ordered mesoporous bioactive glasses with superior in vitro bone-forming bioactivities. Angew. Chem. Int. Ed. Engl. 2004, 43, 5980–5984.
  491. Barba, A.; Maazouz, Y.; Diez-Escudero, A.; Rappe, K.; Espanol, M.; Montufar, E.B.; Öhman-Mägi, C.; Persson, C.; Fontecha, P.; Manzanares, M.C.; et al. Osteogenesis by foamed and 3D-printed nanostructured calcium phosphate scaffolds: Effect of pore architecture. Acta Biomater. 2018, 79, 135–147.
  492. Cosijns, A.; Vervaet, C.; Luyten, J.; Mullens, S.; Siepmann, F.; van Hoorebeke, L.; Masschaele, B.; Cnudde, V.; Remon, J.P. Porous hydroxyapatite tablets as carriers for low-dosed drugs. Eur. J. Pharm. Biopharm. 2007, 67, 498–506.
  493. Uchida, A.; Shinto, Y.; Araki, N.; Ono, K. Slow release of anticancer drugs from porous calcium hydroxyapatite ceramic. J. Orthop. Res. 1992, 10, 440–445.
  494. Shinto, Y.; Uchida, A.; Korkusuz, F.; Araki, N.; Ono, K. Calcium hydroxyapatite ceramic used as a delivery system for antibiotics. J. Bone. Joint. Surg. Br. 1992, 74, 600–604.
  495. Martin, R.B.; Chapman, M.W.; Sharkey, N.A.; Zissimos, S.L.; Bay, B.; Shors, E.C. Bone ingrowth and mechanical properties of coralline hydroxyapatite 1 yr after implantation. Biomaterials 1993, 14, 341–348.
  496. Kazakia, G.J.; Nauman, E.A.; Ebenstein, D.M.; Halloran, B.P.; Keaveny, T.M. Effects of in vitro bone formation on the mechanical properties of a trabeculated hydroxyapatite bone substitute. J. Biomed. Mater. Res. A 2006, 77A, 688–699.
  497. Hing, K.A.; Best, S.M.; Tanner, K.E.; Bonfield, W.; Revell, P.A. Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes. J. Biomed. Mater. Res. A 2004, 68A, 187–200.
  498. Vuola, J.; Taurio, R.; Goransson, H.; Asko-Seljavaara, S. Compressive strength of calcium carbonate and hydroxyapatite implants after bone marrow induced osteogenesis. Biomaterials 1998, 19, 223–227.
  499. Von Doernberg, M.C.; von Rechenberg, B.; Bohner, M.; Grünenfelder, S.; van Lenthe, G.H.; Müller, R.; Gasser, B.; Mathys, R.; Baroud, G.; Auer, J. In vivo behavior of calcium phosphate scaffolds with four different pore sizes. Biomaterials 2006, 27, 5186–5198.
  500. Mygind, T.; Stiehler, M.; Baatrup, A.; Li, H.; Zou, X.; Flyvbjerg, A.; Kassem, M.; Bunger, C. Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds. Biomaterials 2007, 28, 1036–1047.
  501. Mankani, M.H.; Afghani, S.; Franco, J.; Launey, M.; Marshall, S.; Marshall, G.W.; Nissenson, R.; Lee, J.; Tomsia, A.P.; Saiz, E. Lamellar spacing in cuboid hydroxyapatite scaffolds regulates bone formation by human bone marrow stromal cells. Tissue Eng. A 2011, 17, 1615–1623.
  502. Chan, O.; Coathup, M.J.; Nesbitt, A.; Ho, C.Y.; Hing, K.A.; Buckland, T.; Campion, C.; Blunn, G.W. The effects of microporosity on osteoinduction of calcium phosphate bone graft substitute biomaterials. Acta Biomater. 2012, 8, 2788–2794.
  503. Holmes, R.E. Bone regeneration within a coralline hydroxyapatite implant. Plast. Reconstr. Surg. 1979, 63, 626–633.
  504. Tsuruga, E.; Takita, H.; Wakisaka, Y.; Kuboki, Y. Pore size of porous hydoxyapatite as the cell-substratum controls BMP-induced osteogenesis. J. Biochem. 1997, 121, 317–324.
  505. LeGeros, R.Z.; LeGeros, J.P. Calcium phosphate bioceramics: Past, present, future. Key Eng. Mater. 2003, 240–242, 3–10.
  506. Woodard, J.R.; Hilldore, A.J.; Lan, S.K.; Park, C.J.; Morgan, A.W.; Eurell, J.A.C.; Clark, S.G.; Wheeler, M.B.; Jamison, R.D.; Wagoner Johnson, A.J. The mechanical properties and osteoconductivity of hydroxyapatite bone scaffolds with multi-scale porosity. Biomaterials 2007, 28, 45–54.
  507. Jacovella, P.F.; Peiretti, C.B.; Cunille, D.; Salzamendi, M.; Schechtel, S.A. Long-lasting results with hydroxylapatite (Radiesse) facial filler. Plast. Reconstr. Surg. 2006, 118, 15S–21S.
  508. Rustom, L.E.; Poellmann, M.J.; Wagoner Johnson, A.J. Mineralization in micropores of calcium phosphate scaffolds. Acta Biomater. 2019, 83, 435–455.
  509. Levitt, G.E.; Crayton, P.H.; Monroe, E.A.; Condrate, R.A. Forming methods for apatite prosthesis. J. Biomed. Mater. Res. 1969, 3, 683–685.
  510. Fukuba, S.; Okada, M.; Nohara, K.; Iwata, T. Alloplastic bone substitutes for periodontal and bone regeneration in dentistry: Current status and prospects. Materials 2021, 14, 1096.
  511. Dorozhkin, S.V. Dental applications of calcium orthophosphates (CaPO4). J. Dent. Res. 2019, 1, 24–54.
  512. Roca-Millan, E.; Jané-Salas, E.; Marí-Roig, A.; Jiménez-Guerra, Á.; Ortiz-García, I.; Velasco-Ortega, E.; López-López, J.; Monsalve-Guil, L. The application of beta-tricalcium phosphate in implant dentistry: A systematic evaluation of clinical studies. Materials 2022, 15, 655.
  513. Easwer, H.V.; Rajeev, A.; Varma, H.K.; Vijayan, S.; Bhattacharya, R.N. Cosmetic and radiological outcome following the use of synthetic hydroxyapatite porous-dense bilayer burr-hole buttons. Acta Neurochir. 2007, 149, 481–485.
  514. Kashimura, H.; Ogasawara, K.; Kubo, Y.; Yoshida, K.; Sugawara, A.; Ogawa, A. A newly designed hydroxyapatite ceramic burr-hole button. Vasc. Health Risk Manag. 2010, 6, 105–108.
  515. Jordan, D.R.; Gilberg, S.; Bawazeer, A. Coralline hydroxyapatite orbital implant (Bio-Eye): Experience with 158 patients. Ophthal. Plast. Reconstr. Surg. 2004, 20, 69–74.
  516. Yoon, J.S.; Lew, H.; Kim, S.J.; Lee, S.Y. Exposure rate of hydroxyapatite orbital implants. A 15-year experience of 802 cases. Ophthalmology 2008, 115, 566–572.
  517. Tabatabaee, Z.; Mazloumi, M.; Rajabi, T.M.; Khalilzadeh, O.; Kassaee, A.; Moghimi, S.; Eftekhar, H.; Goldberg, R.A. Comparison of the exposure rate of wrapped hydroxyapatite (Bio-Eye) versus unwrapped porous polyethylene (Medpor) orbital implants in enucleated patients. Ophthal. Plast. Reconstr. Surg. 2011, 27, 114–118.
  518. Ma, X.Z.; Bi, H.S.; Zhang, X. Effect of hydroxyapatite orbital implant for plastic surgery of eye in 52 cases. Int. Eye Sci. 2012, 12, 988–990.
  519. Baino, F.; Vitale-Brovarone, C. Bioceramics in ophthalmology. Acta Biomater. 2014, 10, 3372–3397.
  520. Thiesmann, R.; Anagnostopoulos, A.; Stemplewitz, B. Long-term results of the compatibility of a coralline hydroxyapatite implant as eye replacement|Langzeitergebnisse zur Verträglichkeit eines korallinen Hydroxylapatitimplantats als Bulbusersatz. Ophthalmologe 2018, 115, 131–136.
  521. Wehrs, R.E. Hearing results with incus and incus stapes prostheses of hydroxylapatite. Laryngoscope 1991, 101, 555–556.
  522. Smith, J.; Gardner, E.; Dornhoffer, J.L. Hearing results with a hydroxylapatite/titanium bell partial ossicular replacement prosthesis. Laryngoscope 2002, 112, 1796–1799.
  523. Doi, T.; Hosoda, Y.; Kaneko, T.; Munemoto, Y.; Kaneko, A.; Komeda, M.; Furukawa, M.; Kuriyama, H.; Kitajiri, M.; Tomoda, K.; et al. Hearing results for ossicular reconstruction using a cartilage-connecting hydroxyapatite prosthesis with a spearhead. Otol. Neurotol. 2007, 28, 1041–1044.
  524. Thalgott, J.S.; Fritts, K.; Giuffre, J.M.; Timlin, M. Anterior interbody fusion of the cervical spine with coralline hydroxyapatite. Spine 1999, 24, 1295–1299.
  525. Mashoof, A.A.; Siddiqui, S.A.; Otero, M.; Tucci, J.J. Supplementation of autogenous bone graft with coralline hydroxyapatite in posterior spine fusion for idiopathic adolescent scoliosis. Orthopedics 2002, 25, 1073–1076.
  526. Liu, W.Y.; Mo, J.W.; Gao, H.; Liu, H.L.; Wang, M.Y.; He, C.L.; Tang, W.; Ye, Y.J. Nano-hydroxyapatite artificial bone serves as a spacer for fusion with the cervical spine after bone grafting. Chin. J. Tissue Eng. Res. 2012, 16, 5327–5330.
  527. Litak, J.; Czyzewski, W.; Szymoniuk, M.; Pastuszak, B.; Litak, J.; Litak, G.; Grochowski, C.; Rahnama-Hezavah, M.; Kamieniak, P. Hydroxyapatite use in spine surgery–molecular and clinical aspect. Materials 2022, 15, 2906.
  528. Silva, R.V.; Camilli, J.A.; Bertran, C.A.; Moreira, N.H. The use of hydroxyapatite and autogenous cancellous bone grafts to repair bone defects in rats. Int. J. Oral Maxillofac. Surg. 2005, 34, 178–184.
  529. Damron, T.A. Use of 3D β-tricalcium phosphate (Vitoss®) scaffolds in repairing bone defects. Nanomedicine 2007, 2, 763–775.
  530. Zaed, I.; Cardia, A.; Stefini, R. From reparative surgery to regenerative surgery: State of the art of porous hydroxyapatite in cranioplasty. Int. J. Mol. Sci. 2022, 23, 5434.
  531. Alsahafi, R.A.; Mitwalli, H.A.; Balhaddad, A.A.; Weir, M.D.; Xu, H.H.K.; Melo, M.A.S. Regenerating craniofacial dental defects with calcium phosphate cement scaffolds: Current status and innovative scope review. Front. Dent. Med. 2021, 2, 743065.
  532. Bass, L.S.; Smith, S.; Busso, M.; McClaren, M. Calcium hydroxylapatite (Radiesse) for treatment of nasolabial folds: Long-term safety and efficacy results. Aesthetic Surg. J. 2010, 30, 235–238.
  533. Low, K.L.; Tan, S.H.; Zein, S.H.S.; Roether, J.A.; Mouriño, V.; Boccaccini, A.R. Calcium phosphate-based composites as injectable bone substitute materials. J. Biomed. Mater. Res. B Appl. Biomater. 2010, 94B, 273–286.
  534. Daculsi, G.; Uzel, A.P.; Weiss, P.; Goyenvalle, E.; Aguado, E. Developments in injectable multiphasic biomaterials. The performance of microporous biphasic calcium phosphate granules and hydrogels. J. Mater. Sci. Mater. Med. 2010, 21, 855–861.
  535. Suzuki, K.; Anada, T.; Honda, Y.; Kishimoto, K.N.; Miyatake, N.; Hosaka, M.; Imaizumi, H.; Itoi, E.; Suzuki, O. Cortical bone tissue response of injectable octacalcium phosphate-hyaluronic acid complexes. Key Eng. Mater. 2013; 529–530, 296–299.
  536. Pastorino, D.; Canal, C.; Ginebra, M.P. Drug delivery from injectable calcium phosphate foams by tailoring the macroporosity-drug interaction. Acta Biomater. 2015, 12, 250–259.
  537. Moussi, H.; Weiss, P.; le Bideau, J.; Gautier, H.; Charbonnier, B. Injectable macromolecules-based calcium phosphate bone substitutes. Mater. Adv. 2022, 3, 6125–6141.
  538. Bohner, M.; Baroud, G. Injectability of calcium phosphate pastes. Biomaterials 2005, 26, 1553–1563.
  539. Laschke, M.W.; Witt, K.; Pohlemann, T.; Menger, M.D. Injectable nanocrystalline hydroxyapatite paste for bone substitution: In vivo analysis of biocompatibility and vascularization. J. Biomed. Mater. Res. B Appl. Biomater. 2007, 82B, 494–505.
  540. Lopez-Heredia, M.A.; Barnewitz, D.; Genzel, A.; Stiller, M.; Peters, F.; Huebner, W.D.; Stang, B.; Kuhr, A.; Knabe, C. In vivo osteogenesis assessment of a tricalcium phosphate paste and a tricalcium phosphate foam bone grafting materials. Key Eng. Mater. 2015, 631, 426–429.
  541. Torres, P.M.C.; Gouveia, S.; Olhero, S.; Kaushal, A.; Ferreira, J.M.F. Injectability of calcium phosphate pastes: Effects of particle size and state of aggregation of β-tricalcium phosphate powders. Acta Biomater. 2015, 21, 204–216.
  542. Chow, L.C. Next generation calcium phosphate-based biomaterials. Dent. Mater. J. 2009, 28, 1–10.
  543. Victor, S.P.; Kumar, T.S.S. Processing and properties of injectable porous apatitic cements. J. Ceram. Soc. Jpn. 2008, 116, 105–107.
  544. Hesaraki, S.; Nemati, R.; Nosoudi, N. Preparation and characterisation of porous calcium phosphate bone cement as antibiotic carrier. Adv. Appl. Ceram. 2009, 108, 231–240.
  545. Stulajterova, R.; Medvecky, L.; Giretova, M.; Sopcak, T. Structural and phase characterization of bioceramics prepared from tetracalcium phosphate–monetite cement and in vitro osteoblast response. J. Mater. Sci. Mater. Med. 2015, 26, 183.
  546. Bohner, M. Resorbable biomaterials as bone graft substitutes. Mater. Today 2010, 13, 24–30.
  547. Moussa, H.; Jiang, W.; Alsheghri, A.; Mansour, A.; Hadad, A.E.; Pan, H.; Tang, R.; Song, J.; Vargas, J.; McKee, M.D.; et al. High strength brushite bioceramics obtained by selective regulation of crystal growth with chiral biomolecules. Acta Biomater. 2020, 106, 351–359.
  548. Schröter, L.; Kaiser, F.; Stein, S.; Gbureck, U.; Ignatius, A. Biological and mechanical performance and degradation characteristics of calcium phosphate cements in large animals and humans. Acta Biomater. 2020, 117, 1–20.
  549. Paital, S.R.; Dahotre, N.B. Calcium phosphate coatings for bio-implant applications: Materials, performance factors, and methodologies. Mater. Sci. Eng. R 2009, 66, 1–70.
  550. León, B.; Jansen, J.A. (Eds.) Thin Calcium Phosphate Coatings for Medical Implants; Springer: New York, NY, USA, 2009; p. 326.
  551. Dorozhkin, S.V. Calcium orthophosphate deposits: Preparation, properties and biomedical applications. Mater. Sci. Eng. C 2015, 55, 272–326.
  552. Kon, M.; Ishikawa, K.; Miyamoto, Y.; Asaoka, K. Development of calcium phosphate based functional gradient bioceramics. Biomaterials 1995, 16, 709–714.
  553. Wong, L.H.; Tio, B.; Miao, X. Functionally graded tricalcium phosphate/fluoroapatite composites. Mater. Sci. Eng. C 2002, 20, 111–115.
  554. Tampieri, A.; Celotti, G.; Sprio, S.; Delcogliano, A.; Franzese, S. Porosity-graded hydroxyapatite ceramics to replace natural bone. Biomaterials 2001, 22, 1365–1370.
  555. Werner, J.; Linner-Krcmar, B.; Friess, W.; Greil, P. Mechanical properties and in vitro cell compatibility of hydroxyapatite ceramics with graded pore structure. Biomaterials 2002, 23, 4285–4294.
  556. Watanabe, T.; Fukuhara, T.; Izui, H.; Fukase, Y.; Okano, M. Properties of HAp/β-TCP functionally graded material by spark plasma sintering. Trans. Jpn. Soc. Mech. Eng. A 2009, 75, 612–618.
  557. Bai, X.; Sandukas, S.; Appleford, M.R.; Ong, J.L.; Rabiei, A. Deposition and investigation of functionally graded calcium phosphate coatings on titanium. Acta Biomater. 2009, 5, 3563–3572.
  558. Tamura, A.; Asaoka, T.; Furukawa, K.; Ushida, T.; Tateishi, T. Application of α-TCP/HAp functionally graded porous beads for bone regenerative scaffold. Adv. Sci. Technol. 2013, 86, 63–69.
  559. Gasik, M.; Keski-Honkola, A.; Bilotsky, Y.; Friman, M. Development and optimisation of hydroxyapatite-β-TCP functionally gradated biomaterial. J. Mech. Behav. Biomed. Mater. 2014, 30, 266–273.
  560. Zhou, C.; Deng, C.; Chen, X.; Zhao, X.; Chen, Y.; Fan, Y.; Zhang, X. Mechanical and biological properties of the micro-/nano-grain functionally graded hydroxyapatite bioceramics for bone tissue engineering. J. Mech. Behav. Biomed. Mater. 2015, 48, 1–11.
  561. Marković, S.; Lukić, M.J.; Škapin, S.D.; Stojanović, B.; Uskoković, D. Designing, fabrication and characterization of nanostructured functionally graded HAp/BCP ceramics. Ceram. Int. 2015, 41, 2654–2667.
  562. Salimi, E. Functionally graded calcium phosphate bioceramics: An overview of preparation and properties. Ceram. Int. 2020, 46, 19664–19668.
  563. Freidlin, L.K.; Sharf, V.Z. Two paths for the dehydration of 1,4-butandiol to divinyl with a tricalcium phosphate catalyst. Bull. Acad. Sci. USSR Div. Chem. Sci. 1960, 9, 1577–1579.
  564. Bett, J.A.S.; Christner, L.G.; Hall, W.K. Studies of the hydrogen held by solids. XII. Hydroxyapatite catalysts. J. Am. Chem. Soc. 1967, 89, 5535–5541.
  565. Monma, H. Catalytic behavior of calcium phosphates for decompositions of 2-propanol and ethanol. J. Catal. 1982, 75, 200–203.
  566. Tsuchida, T.; Yoshioka, T.; Sakuma, S.; Takeguchi, T.; Ueda, W. Synthesis of biogasoline from ethanol over hydroxyapatite catalyst. Ind. Eng. Chem. Res. 2008, 47, 1443–1452.
  567. Tsuchida, T.; Kubo, J.; Yoshioka, T.; Sakuma, S.; Takeguchi, T.; Ueda, W. Reaction of ethanol over hydroxyapatite affected by Ca/P ratio of catalyst. J. Catal. 2008, 259, 183–189.
  568. Xu, J.; White, T.; Li, P.; He, C.; Han, Y.F. Hydroxyapatite foam as a catalyst for formaldehyde combustion at room temperature. J. Am. Chem. Soc. 2010, 132, 13172–13173.
  569. Hatano, M.; Moriyama, K.; Maki, T.; Ishihara, K. Which is the actual catalyst: Chiral phosphoric acid or chiral calcium phosphate? Angew. Chem. Int. Ed. Engl. 2010, 49, 3823–3826.
  570. Zhang, D.; Zhao, H.; Zhao, X.; Liu, Y.; Chen, H.; Li, X. Application of hydroxyapatite as catalyst and catalyst carrier. Prog. Chem. 2011, 23, 687–694.
  571. Gruselle, M.; Kanger, T.; Thouvenot, R.; Flambard, A.; Kriis, K.; Mikli, V.; Traksmaa, R.; Maaten, B.; Tõnsuaadu, K. Calcium hydroxyapatites as efficient catalysts for the Michael C–C bond formation. ACS Catal. 2011, 1, 1729–1733.
  572. Stošić, D.; Bennici, S.; Sirotin, S.; Calais, C.; Couturier, J.L.; Dubois, J.L.; Travert, A.; Auroux, A. Glycerol dehydration over calcium phosphate catalysts: Effect of acidic-basic features on catalytic performance. Appl. Catal. A 2012, 447–448, 124–134.
  573. Ghantani, V.C.; Lomate, S.T.; Dongare, M.K.; Umbarkar, S.B. Catalytic dehydration of lactic acid to acrylic acid using calcium hydroxyapatite catalysts. Green Chem. 2013, 15, 1211–1217.
  574. Chen, G.; Shan, R.; Shi, J.; Liu, C.; Yan, B. Biodiesel production from palm oil using active and stable K doped hydroxyapatite catalysts. Energ. Convers. Manage. 2015, 98, 463–469.
  575. Gruselle, M. Apatites: A new family of catalysts in organic synthesis. J. Organomet. Chem. 2015, 793, 93–101.
  576. Urist, M.R.; Huo, Y.K.; Brownell, A.G.; Hohl, W.M.; Buyske, J.; Lietze, A.; Tempst, P.; Hunkapiller, M.; de Lange, R.J. Purification of bovine bone morphogenetic protein by hydroxyapatite chromatography. Proc. Natl. Acad. Sci. USA 1984, 81, 371–375.
  577. Kawasaki, T. Hydroxyapatite as a liquid chromatographic packing. J. Chromatogr. 1991, 544, 147–184.
  578. Kuiper, M.; Sanches, R.M.; Walford, J.A.; Slater, N.K.H. Purification of a functional gene therapy vector derived from moloney murine leukaemia virus using membrane filtration and ceramic hydroxyapatite chromatography. Biotechnol. Bioeng. 2002, 80, 445–453.
  579. Jungbauer, A.; Hahn, R.; Deinhofer, K.; Luo, P. Performance and characterization of a nanophased porous hydroxyapatite for protein chromatography. Biotechnol. Bioeng. 2004, 87, 364–375.
  580. Wensel, D.L.; Kelley, B.D.; Coffman, J.L. High-throughput screening of chromatographic separations: III. Monoclonal antibodies on ceramic hydroxyapatite. Biotechnol. Bioeng. 2008, 100, 839–854.
  581. Hilbrig, F.; Freitag, R. Isolation and purification of recombinant proteins, antibodies and plasmid DNA with hydroxyapatite chromatography. Biotechnol. J. 2012, 7, 90–102.
  582. Cummings, L.J.; Frost, R.G.; Snyder, M.A. Monoclonal antibody purification by ceramic hydroxyapatite chromatography. Method Mol. Biol. 2014, 1131, 241–251.
  583. Nagai, M.; Nishino, T.; Saeki, T. A new type of CO2 gas sensor comprising porous hydroxyapatite ceramics. Sens. Actuator 1988, 15, 145–151.
  584. Petrucelli, G.C.; Kawachi, E.Y.; Kubota, L.T.; Bertran, C.A. Hydroxyapatite-based electrode: A new sensor for phosphate. Anal. Commun. 1996, 33, 227–229.
  585. Tagaya, M.; Ikoma, T.; Hanagata, N.; Chakarov, D.; Kasemo, B.; Tanaka, J. Reusable hydroxyapatite nanocrystal sensors for protein adsorption. Sci. Technol. Adv. Mater. 2010, 11, 045002.
  586. Khairnar, R.S.; Mene, R.U.; Munde, S.G.; Mahabole, M.P. Nano-hydroxyapatite thick film gas sensors. AIP Conf. Proc. 2011, 1415, 189–192.
  587. López, M.S.P.; Redondo-Gómez, E.; López-Ruiz, B. Electrochemical enzyme biosensors based on calcium phosphate materials for tyramine detection in food samples. Talanta 2017, 175, 209–216.
  588. Nijhawan, A.; Butler, E.C.; Sabatini, D.A. Hydroxyapatite ceramic adsorbents: Effect of pore size, regeneration, and selectivity for fluoride. J. Environ. Eng. 2018, 144, 04018117.
  589. Ibrahim, M.; Labaki, M.; Giraudon, J.M.; Lamonier, J.F. Hydroxyapatite, a multifunctional material for air, water and soil pollution control: A review. J. Hazard. Mater. 2020, 383, 121139.
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