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Dorozhkin, S.V. Biomedical Applications of CaPO4 Deposits. Encyclopedia. Available online: (accessed on 20 June 2024).
Dorozhkin SV. Biomedical Applications of CaPO4 Deposits. Encyclopedia. Available at: Accessed June 20, 2024.
Dorozhkin, Sergey V.. "Biomedical Applications of CaPO4 Deposits" Encyclopedia, (accessed June 20, 2024).
Dorozhkin, S.V. (2023, July 05). Biomedical Applications of CaPO4 Deposits. In Encyclopedia.
Dorozhkin, Sergey V.. "Biomedical Applications of CaPO4 Deposits." Encyclopedia. Web. 05 July, 2023.
Biomedical Applications of CaPO4 Deposits

The clinical applications of CaPO4 alone were largely limited to non-load-bearing areas of the body. However, investigations have continued and researchers have begun to deposit biocompatible CaPO4 on the surface of mechanically strong but biologically inert or biotoxic materials in order to combine the benefits of various materials. For example, metal implants are used in artificial joints such as hip joints and artificial tooth roots as sufficient mechanical stability is required.  Since no metal alone causes osseointegration, i.e., they do not create a mechanically stable connection between the implant and bone tissue, they are coated with CaPO4 to create osseointegration. However, the problem of osseointegration is not limited to metals. Biodegradable polymers are also generally not bioactive. Therefore, to overcome this disadvantage, the surface of those polymers is also coated with CaPO4 and can be replaced by autogenous bone after implantation, as CaPO4 is involved in the same bone regeneration response as natural bones.

biomedical CaPO4

1. Introduction

All known materials have their own specific properties and, depending on the applications, those properties may or may not be desirable. That is, certain ones are aggressive, corrosive or biotoxic; others are sensitive to light, heat and oxidation; some are hydrophilic, transparent, slimy, etc. To eliminate the undesirable properties, the surfaces of improper materials need to be modified. This resulted in the appearance of a specialized sub-discipline of materials science called surface engineering, which modifies the surfaces of solid materials in various ways. In a broad sense, surface engineering has applications in chemistry, and mechanical and electrical engineering (especially in relation to semiconductor manufacturing) [1], which is beyond the scope of this research.
Generally, surface modifications can be broadly divided into three categories: (1) depositing a material onto a surface with desired function and properties; (2) transforming an existing surface into a more desirable composition, structure or morphology; (3) partially removing material from an existing surface to create a specific topography [2]. As can be seen from the list of the options, the first two categories involve the application of surface deposits (coatings, films and layers) to solve problems in traditional forms. Regarding biomaterials, their properties are likely to be important when they are implanted in the human body. That is, in the case of artificial bone grafts, synthetic materials used in vivo must have appropriate properties, both surface and bulk, to meet the dual requirements of biocompatibility and application-specific mechanical properties. That is why cytotoxic, genotoxic, allergic, neurotoxic, carcinogenic and mutagenic factors are considered when evaluating the biomedical properties of orthopedic implant materials [2]. To meet all these requirements, the surfaces of bioincompatible materials can be modified with appropriate deposits (coatings, films and layers) to create favorable surface conditions for adsorption of proteins from biological fluids and to promote cell–extracellular matrix interactions and production of growth factors. Otherwise, either fibrous tissue will surround implants made of bioincompatible materials or mechanically weak grafts will not function properly. Both types of defects prolong the healing time. Therefore, diverse surface treatments have been developed to improve the biocompatibility and osteoconductivity of artificial implants [3].
On the other hand, some compounds, such as calcium orthophosphates (abbreviated as CaPO4), are well suited to in vivo applications due to their chemical similarity to the inorganic substances found in mammalian bones and teeth [4][5][6]. However, since all types of CaPO4 are ceramic, they are all mechanically weak (brittle) and cannot be subjected to physiological loads (other than compressive ones) occurring in the human skeleton. For many years, therefore, the clinical applications of CaPO4 alone were largely limited to non-load-bearing areas of the body. However, investigations have continued and researchers have begun to deposit biocompatible CaPO4 on the surface of mechanically strong but biologically inert or biotoxic materials in order to combine the benefits of various materials [7][8]. For example, metal implants are used in artificial joints such as hip joints and artificial tooth roots as sufficient mechanical stability is required. Since no metal alone causes osseointegration, i.e., they do not create a mechanically stable connection between the implant and bone tissue, they are coated with CaPO4 to create osseointegration. However, the problem of osseointegration is not limited to metals. Biodegradable polymers are also generally not bioactive. Therefore, to overcome this disadvantage, the surface of those polymers is also coated with CaPO4 and can be replaced by autogenous bone after implantation, as CaPO4 is involved in the same bone regeneration response as natural bones [7][8][9][10][11][12][13][14][15].
However, in order to successfully fulfill the important functions (i.e., bioactive adaptation of biologically inert implants), all types of CaPO4 deposits (coatings, films and layers) must meet a number of requirements. The minimum requirements for HA coatings first appeared in the 1992 US guidelines of the Food and Drug Administration (FDA) [16] and sometime later in the International Organization for Standardization (ISO) standards [17]. Subsequently, the FDA guidelines were updated in 1997 [18] and the ISO standards in 2000 [19], 2008 [20] and 2018 [21]. In addition, there is a 2002 ISO standard for the determination of HA coating adhesion strength [22], which was revised in 2018 [23]. In short, important quality characteristics for CaPO4 deposits include thickness, phase composition, crystallinity, Ca/P ratio, microstructure, porosity, surface texture and roughness. All these parameters are likely to affect the mechanical properties of CaPO4 deposits such as cohesion, bond strength, tensile strength, shear strength, Young’s modulus, fatigue life and residual stress.

2. Biomedical Applications of CaPO4 Deposits

The first patent for development of thermal sprayed HA deposits on metal implants was issued in 1979 [24]. The results of the first clinical trials were published in 1987 [25]. Shortly thereafter two leading surgeons in the field of orthopedic surgery, Furlong and Osborn, began implanting plasma-spray-deposited HA stems in patients [26]. Other clinicians followed their lead [27][28]. Since then, many scientific publications have been reported on the benefits of CaPO4-coated implants. Summarizing the available information on the biomechanical and biomedical properties of CaPO4-deposited implants, the following data can be claimed. Compared to uncoated controls, deposited CaPO4 improved bone-implant contact [29][30][31][32][33][34][35][36][37][38], initial stability [39], implant fixation [40][41][42][43][44][45] and nanomechanical properties of adjacent bone [46], higher torque values [33][34][45][47] and extrusion strength [48], protecting the interface from wear particles [49], closing small gaps [50][51], reducing ion emissions from metal substrate [52][53][54][55], retarding metal degradation and corrosion [56][57][58][59][60][61][62][63][64], bone growth [65][66][67], remodeling [68][69], osteointegration [70][71][72][73][74][75][76], improving biocompatibility [77], osteoconductivity [29][60][78][79][80][81][82][83][84], osteoinductivity [85], bone immunomodulation [86], osteogenesis [37][45][87][88][89], early bone [44][71][89][90][91] and healing [92] responses, prevention of fibrous tissue formation [93][94], ectopic bone formation [95], osteoblast density [96] and osteoblast proliferation [97], and improvement of the clinical performance of orthopedic hips. Furthermore, the antimicrobial properties of deposited CaPO4 have been detected in several studies [56][96]. Remarkably, to improve osteoinductive properties, biphasic formulations HA + β-TCP were coated with nanosized HA [98][99]. It should be emphasized that all those cases represent a range of positive effects of CaPO4 deposition by different techniques but comparative studies have revealed that these effects are highly dependent on the deposition technique. That is, compared to uncoated controls, electrochemically deposited CaPO4 was found to contribute to bone-implant fixation, while biomimetic deposition had little effect on fixation [100].
CaPO4 can be deposited as various biocomposites with numerous additives. Among them, drugs, amino acids, and other biologically active compounds such as hormones, peptides, genes, growth factors and DNA are present [101][102][103][104][105][106][107][108][109][110][111][112][113][114]. Antibiotic-containing CaPO4 deposits were found to show significant in vivo improvements in infection prevention when compared to just CaPO4 deposits [106][111][112][113][114]. Similar effects were also seen in Ag-doped deposits [115][116][117][118][119][120][121][122][123][124][125][126]. These bioactive molecule delivery methods extend the function of CaPO4 deposits to promote new bone formation in orthopedic implants. However, there are still many open questions regarding the incorporation method and optimal release kinetics of antibiotics.
In the case of porous implants, the deposited CaPO4 facilitate bone penetration within the pores [127]. Furthermore, one study concluded that there was significantly less pin loosening in the CaPO4-treated group [128]. Thus, many clinical studies are optimistic about the in vivo performance of CaPO4-stored implants. Nevertheless, for the sake of objectivity, it is also necessary to mention the studies in which no positive effects were found [129][130]. Furthermore, the presence or absence of the positive effects may depend on the deposition method [100][131][132] and the coating supplier [133]. Moreover, the application or non-application of post-deposition treatments also affects the biological response of CaPO4 deposits [134]. These uncertainties may be due to several reasons, including variations in chemical and phase composition, porosity and additives, as well as various surgeon and patient factors that often confound clinical trials.
In biomedical applications, bone grafts are usually much thicker than the CaPO4 deposits applied on them. Thus, the coated implants combine the surface biocompatibility and bioactivity of CaPO4 with the core strength of a strong substrate [135]. Clinical results of coated implants reveal a much longer post-implantation lifetime than uncoated devices and are therefore particularly beneficial for younger patients [136]. Their biomedical properties approach those of bioactive glass-coated implants [137][138].
Among the available CaPO4 compounds, HA seems to be the most popular deposition material, so most of the clinical studies have been performed with HA. Namely, HA coatings as an in vivo fixation system for hip implants have been found to perform well in the short to medium term: 2 years [139], 5 years [140], 6 years [141], 8 years [142][143], 9 to 12 years [144], 10 years [145][146][147], 10 to 13 years [147], 10 to 15.8 years [148], 10 to 17 years [149], 13 to 15 years [150], 15 years [151], 15 to 21 years [152], 16 years [153], 17 years [154], 17 to 25 years [155], 18 years [156], 19 years [157], 25–30 years [158] and 30–35 years [159]. Similar data have been obtained for HA-coated [160][161][162][163][164] and biphasic HA + TCP coated [165] dental implants. Longer-term clinical results are still awaited with great interest. Additional details on this topic can be found in the references [166][167][168][169][170][171].
At the end of this section, it should be emphasized that many in vivo studies on CaPO4 deposits have shown stronger and faster fixations, more bone growth at the interface, etc., but not all types of CaPO4 deposits give the same results [172][173]. Furthermore, negative results should always be kept in mind and the reasons for this should be carefully investigated and understood. Thus, the clinical applications of CaPO4 deposits are still far from faultlessness. The main areas of concern are listed below [174][175][176]:
In vivo degradation and resorption of CaPO4 deposits can lead to a loss of bond strength between the substrate and the coating, which can hinder implant fixation.
Delamination and delamination of deposits can induce the formation of particle debris.
CaPO4 deposited on polymers may also alleviate osteolysis problems by causing increased polymer wear from the acetabular cup.
In addition, in vivo studies are still scarce in the literature. The limitations of such experiments can be attributed to the following reasons:
It is difficult to select an appropriate animal model to simulate the actual mechanical loading and unloading states to which an implant may be subjected in a human environment.
Normally, experiments require the sacrificing of many animals because of the statistical analysis needed to validate the results.
These experiments demand high costs and long clinical trial durations.
The lack of collaboration between materials scientists and biologists has led to a lack of understanding of this interdisciplinary topic.
The use of animals in experiments raises serious ethical issues because of the painful procedures and exposure to poisons that occur during experiments.


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Video Production Service