Calcium phosphate bioceramics are materials made of calcium ions (Ca²⁺) and phosphate ions (H₂PO₄⁻, HPO₄²⁻, or PO₄³⁻). Several compounds belong to this family, with different stoichiometries and different phosphate species. They are specifically identified in biomaterials science by their calcium-to-phosphorus atomic ratio (Ca/P)_at. (Table 1).

. Regular surface morphologies are more efficient for bone cell attachment than irregular and sharp ones ^[56][186]. According to Cairns et al., they significantly promote the expression of growth factors involved in bone formation in comparison with sharp surfaces made of needles ^[57][58][187,188].

Bioactivity is a surface phenomenon influenced by, among other factors, the roughness of materials. High roughness exceeding 2 µm is not appropriate, because the long distances between valleys and peaks prevent the formation of the osteoblastic pseudopodia required for bone cell adhesion ^[59][60][61][189,190,191]. Calcium phosphate coatings with roughness values in the range of 0.5 to 1.5 μm are generally described to be the most interesting for the promotion of bone cell activity ^[62][63][64][192,193,194].

The porosity of calcium phosphate coatings has a significant impact on the bioactive behavior of bone implants in a physiological environment. Pores larger than one hundred micrometers (macroporosity) support the growth of bone tissues through the coating and improve the connection between newly formed bone cells. However, these large pores also strongly reduce the mechanical properties of the bioceramic coatings ^[65][195]. Smaller pores of a few tens of micrometers and below (microporosity) enhance protein adsorption, body fluid circulation, and the resorption rate of the coating ^[66][196].

Surface wettability is a key property of calcium phosphate coatings because the bioactivity processes occur in a liquid medium. Contact angle (θ) measurements are used to quantify the wetting behavior of a drop of physiological solution deposited on the coating surface ^[67][68][69][197,198,199]. As a function of the contact angle value, the surface is qualified as hydrophilic or hydrophobic.

Biomaterials with hydrophilic surfaces are more effective in promoting chemical and biological interactions with the physiological environment ^[70][71][201,202].

The adhesion of calcium phosphate coatings is the main mechanical property required by the biomedical market ^{[72][73][74][75][76][77]}[104,203,204,205,206,207]. The value of coatings is determined by performing tensile adhesion measurements according to the international standard ISO 13779-4 ^[78][208].

The measurement requires a Ti6Al4V cylinder (25 mm in diameter and 25 mm in height) with one surface coated with calcium phosphate. The coated surface is attached to another Ti6Al4V cylinder by adhesive glue. The entire system is introduced into a standard tensile machine where an increasing load is applied until the separation of the coating is achieved by the breaking of the interface with the initially coated cylinder. A cohesive failure inside the coating may also occur, but in this case, the measurement is not valid and must be repeated. A minimum of five measurements of adhesive failure is necessary to obtain an average adhesion value. The bone implant industry requires adhesion values higher than 15 MPa ^[78][208].

This protocol is standardized for industrial applications, but several other methods can be used to determine the adhesion of calcium phosphate coatings, including the peel test, the scratch test, the ultrasonic test, and the laser shock adhesion test ^{[72][79][80][81][82][83]}[104,209,210,211,212,213].

The bioactivity and biological properties of calcium phosphate coatings can be improved by means of ionic substitution ^{[84][85][86][87][88][89][90][91][92][93]}[214,215,216,217,218,219,220,221,222,223]. The objective is to release the substituting ions in the physiological environment after implantation, taking advantage of the dissolution process (see Section 2). Several ionic substitutions have been described in the literature, using monovalent cations, divalent cations, trivalent cations, or anions. They are used to impart the various biological or chemical effects described in Table 2.

The stoichiometry of a calcium phosphate coating affects its solubility in a physiological environment, which is the first step involved in the bioactivity process after implantation.

The partial dissolution of the calcium phosphate coating in contact with the physiological environment induces ionic releases. The local concentrations of calcium and phosphate ions increase up to supersaturation, which triggers the precipitation of biological apatite at the interface between the implant and the surrounding bone tissues ^{[34][35][36][37][38][39]}[30,31,35,36,37,38]. After these first chemical steps, the biological steps start, involving bone cell attachment, proliferation, and differentiation. In the last step of the bioactivity process, the bone cells trigger the formation of the extracellular matrix (ECM), which is a three-dimensional network of macromolecules and minerals, such as collagen, enzymes, glycoproteins, and apatite ^[40][41][42][88,89,90]. The function of the extracellular matrix is to provide structural and biochemical support to the surrounding bone cells to promote their development ^[43][91]. Due to the bioactivity of the calcium phosphate coatings, bone-like apatite is formed at the interface between the bone implant and the bone tissue. This bone-like apatite layer is a direct, adherent, and strong bonding that results in the long-term stability of the bone implant inside the human body ^[44][92]. However, the success of the bioactivity process is related to several properties of the calcium phosphate coating and not only to the stoichiometry and solubility of the bioceramic material. The choice of the process and the experimental deposition conditions may influence many physicochemical properties of the calcium phosphate coating, and consequently the bioactivity process.

In addition to stoichiometry and solubility, several physicochemical properties impact the bioactivity of calcium phosphate coatings immersed in a physiological environment. Crystallinity, morphology, roughness, porosity, wettability, adhesion, and ionic substitution are the most important ones.

The crystallinity of calcium phosphate coatings impacts their solubility in a physiological environment. The more crystallized the coating, the more stable it is in solution ^[45][46][47][175,176,177]. Crystallinity can be controlled by post-deposition thermal annealing. The international standard ISO 13779-2 recommends a degree of crystallinity higher than 45% for the biomedical market of bone implants ^[48][178]. However, as a function of the annealing temperature, several phases can form in addition to the calcium phosphate phases ^[49][50][179,180]. To maintain a low level of cytotoxicity, the quantity of secondary phases (for example CaO) in the calcium phosphate coatings should be below 5 wt.% ^[48][178]. The methods for determining the crystallinity of calcium phosphate coatings and the quantity of secondary phases are comprehensively described in the international standard ISO 13779-3 ^[51][181].

The surface morphology of calcium phosphate coatings affects the bone cells’ attachment, growth, proliferation, and differentiation ^[52][53][182,183]. As a function of the deposition process and the experimental conditions, the surface morphology of the coatings can change ^[54][55][184,185]

A few percent of these ions are generally used to produce substituted calcium phosphate coatings. Multi-substitution with several substituting ions is also described in the literature with the objective of cumulating its positive effects on the biological properties of bone implants ^{[161][162][163][164][165][166][167][168][169][170][171][172][173][174][175]}[291,292,293,294,295,296,297,298,299,300,301,302,303,304,305].