Calcium Phosphate-based Materials Research Articles

Effects of inorganic phosphate on stem cells isolated from human exfoliated deciduous teeth

Calcium phosphate-based materials (CaP) are introduced as potential dental pulp capping materials for deciduous teeth. The present study investigated the influence of inorganic phosphate (Pi) on regulating stem cells isolated from human exfoliated deciduous teeth (SHED). SHEDs were treated with Pi. Cell cycle progression and apoptosis were examined using flow cytometry analysis. Osteo/odontogenic and adipogenic differentiation were analyzed using alizarin red S and oil red O staining, respectively. The mRNA expression profile was investigated using a high-throughput RNA sequencing technique. Pi increased the late apoptotic cell population while cell cycle progression was not altered. Pi upregulated osteo/odontoblastic gene expression and enhanced calcium deposition. Pi-induced mineralization was reversed by pretreatment of cells with Foscarnet, or p38 inhibitor. Pi treatment inhibited adipogenic differentiation as determined by decreased PPARγ expression and reduced intracellular lipid accumulation. Bioinformatic analysis of gene expression profiles demonstrated several involved pathways, including PI3K/AKT, MAPK, EGFR, and VEGF signaling. In conclusion, Pi enhanced osteo/odontogenic but inhibited adipogenic differentiation in SHED.

An effective cascade strategy over a Sn-enriched phosphate material: Upcycling a reductive adsorbent into an environmental catalyst

A calcium phosphate-based material enriched with Sn (8.3 at.%, as revealed by X-ray photoelectron spectroscopy) was successfully used in the reductive adsorption of Cr(VI) to Cr(III) for water remediation and, after use, repurposed into a catalyst for NO oxidation into NO2.The use of multiple characterization techniques (Mӧssbauer spectroscopy, synchrotron X-ray diffraction, TEM, and HAADF-STEM/EDS) provided information on Sn-speciation (Sn(II)/Sn(IV) = 1.2), structural composition, and morphological features. Cassiterite (rutile-type SnO2) and hydroromarchite (tin oxide-hydroxide Sn6O4(OH)4) crystalline phases characterized the material, along with the presence of an amorphous Ca3(PO4)2 phase.Notably, about 15 mgCr(VI)∙g−1 could be effectively reduced over a broad pH range (2–11), even in the simultaneous presence of various anions and cations, with concurrent adsorption of the resulting Cr(III), thanks to the adsorption properties of the phosphate phase. The kinetic constant of Cr(VI) removal was as high as 0.0058 g∙mg−1∙min−1 and increased in the presence of a pool of cations (0.0147 g∙mg−1∙min−1). The catalytic performances of the adsorbent after use in Cr(VI) reductive adsorption were studied in the 150–450 °C interval at 15,000–80,000 h−1 space velocity. About 90 % of NO conversion at 350 °C was observed.This study highlights the adaptability and efficiency of the developed material across different environmental remediation processes.

Investigations on Microstructure and Mechanical Properties of HAp Nanocomposites reinforced with ZrO2 and TiO2

In the contemporary context, approximately 15 million individuals in India grapple with bone-related issues stemming from accidents, fractures, bone mass depletion, and the natural aging process. To address this challenge, a diverse array of biomaterials has been innovated to rectify or enhance bone deficiencies within the human body. Nevertheless, over the past decade, calcium phosphate-based bioceramic materials have gained significant prominence as synthetic alternatives for bone and dental applications in the fields of orthopaedics and dentistry. One such bioactive ceramic, Hydroxyapatite (HAp), boasts exceptional versatility and can find utility in both dental and orthopaedic contexts. In the current research, exhaustive research was conducted to explore the impact of HAp/(ZrO2+TiO2) hybrid nano-composites synthesized through a mechanical synthesis process employing high-energy ball milling (HEBM), incorporating varying weight proportions. The resulting “HAp/(ZrO2+TiO2) nano-composites” were subjected to characterization through scanning electron microscopy combined with energy-dispersive X-ray spectroscopy (SEM-EDX) and X-ray diffraction (XRD). Furthermore, the study assessed the influence of these nano-composites regarding the HAp nano-composites’ mechanical characteristics.

Magnesium-Substituted Brushite Cement: Physical and Mechanical Properties

Brushite cements (BrCs) are calcium phosphate-based materials that are being widely used in hard tissue engineering applications due to their osteoconductivity, injectability, and bioresorbability. Therefore, the goal was to evaluate the effects of Mg concentration on the phase composition, setting time, and strength of BrC. Mg, which plays a vital role in bodily functions and bone health, was added to BrC at concentrations of 0.25, 0.50, 1.00, 1.50, 2.00, and 2.50 wt.%. The results showed that Mg stabilizes the TCP structure and increases the TCP content in final BrC. The initial and final setting times of BrCs increase with higher concentrations of Mg. Although 0.25 wt.% Mg did not change the setting of BrCs significantly, a higher concentration of 1.00 wt.% increased the initial setting time from 4.87 ± 0.38 min to 15.14 ± 0.88 min. Cements with Mg concentrations of 1.5 wt.% and above did not set after 4 h. Mg addition up to 0.5 wt.% did not change the compressive strength; however, higher concentrations decreased it significantly and 2.5 Mg-BrC had the lowest strength of 0.45 ± 0.09 MPs. Together, our results show that Mg can be added up to 1.00 wt.% without any adverse effect on the physical and mechanical properties of BrC.

Development of bioinspired damage-tolerant calcium phosphate bulk materials

ABSTRACT Improving the damage tolerance and reliability of ceramic artificial bone materials, such as sintered bodies of hydroxyapatite (HAp), that remain in vivo for long periods of time is of utmost importance. However, the intrinsic brittleness and low damage tolerance of ceramics make this challenging. This paper reports the synthesis of highly damage tolerant calcium phosphate-based materials with a bioinspired design for novel artificial bones. The heat treatment of isophthalate ion-containing octacalcium phosphate compacts in a nitrogen atmosphere at 1000°C for 24 h produced an HAp/β-tricalcium phosphate/pyrolytic carbon composite with a brick-and-mortar structure (similar to that of the nacreous layer). This composite exhibited excellent damage tolerance, with no brittle fracture upon nailing, likely attributable to the specific mechanical properties derived from its unique microstructure. Its maximum bending stress, maximum bending strain, Young’s modulus, and Vickers hardness were 11.7 MPa, 2.8 × 10‒ 2, 5.3 GPa, and 11.7 kgf/mm2, respectively. The material exhibited a lower Young’s modulus and higher fracture strain than that of HAp-sintered bodies and sintered-body samples prepared from pure octacalcium phosphate compacts. Additionally, the apatite-forming ability of the obtained material was confirmed in vitro, using a simulated body fluid. The proposed bioinspired material design could enable the fabrication of highly damage tolerant artificial bones that remain in vivo for long durations of time.

Mechanochemical synthesis and characterization of strontium substituted apatite for biomedical application

Strontium-substituted apatite has been proposed as a promising material for osteoporosis treatment. Several synthesis methods have been attempted in the past. In this study, we investigated a method known as the mechanochemical synthesis method. Characterization was carried out using different amounts of strontium ions in the hydroxyapatite (HAp) matrix with FT-IR spectral analysis, X-ray diffraction, lattice constant measurements, differential thermal analysis (DTA), terahertz spectroscopy, and investigation of the basic morphology using scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX). We report that the development and performance of mechanochemical synthetic pathways are more efficient and economical than other substituted apatite formation methods and are useful in the biomedical field to produce calcium phosphate-based clinical materials. The FTIR spectra, terahertz spectra, and XRD analysis results revealed that the mixture of dicalcium phosphate dihydrate (DCPD), Ca(OH)2 and Sr(OH)2 8H2O was phase-transformed into strontium-containing carbonate amorphous apatite by this simple and economical mechanochemical synthesis method.

Advances in new materials for bone tissue engineering simplifying postoperative rehabilitation: Recent Scientific Breakthroughs

Introduction: Bone tissue engineering has emerged as a promising field in regenerative medicine, aiming to develop innovative materials and approaches for bone repair and regeneration, which also leads to the simplification and search for new approaches in postoperative rehabilitation. The integration of novel materials into scaffolds and implants plays a crucial role in improving bone tissue engineering strategies. In recent years, scientific research has made significant progress in identifying and characterizing novel materials with superior properties and functionalities.
 Aim: This article explores the most recent scientific findings and research breakthroughs concerning novel materials for bone tissues, focusing on their biocompatibility, mechanical properties, bioactivity, and potential clinical applications.
 Conclusion: In recent years, the field of bone tissue engineering has witnessed remarkable advancements in the development of novel materials for bone repair and regeneration, which also simplify the medical rehabilitation of the patient. From bioactive glasses and calcium phosphate-based materials to biodegradable magnesium-based materials and graphene-based composites, researchers have explored a wide range of materials with diverse properties and functionalities. As the field continues to evolve, the integration of cutting-edge technologies, such as 3D printing and nanotechnology, is expected to further enhance the efficacy and clinical relevance of these novel materials, ultimately benefiting patients with bone defects and diseases.

Robocasting of Ceramic Fischer-Koch S Scaffolds for Bone Tissue Engineering.

Triply Periodic Minimal Surfaces (TPMS) are promising structures for bone tissue engineering scaffolds due to their relatively high mechanical energy absorption, smoothly interconnected porous structure, scalable unit cell topology, and relatively high surface area per volume. Calcium phosphate-based materials, such as hydroxyapatite and tricalcium phosphate, are very popular scaffold biomaterials due to their biocompatibility, bioactivity, compositional similarities to bone mineral, non-immunogenicity, and tunable biodegradation. Their brittle nature can be partially mitigated by 3D printing them in TPMS topologies such as gyroids, which are widely studied for bone regeneration, as evidenced by their presence in popular 3D-printing slicers, modeling systems, and topology optimization tools. Although structural and flow simulations have predicted promising properties of other TPMS scaffolds, such as Fischer-Koch S (FKS), to the best of our knowledge, no one has explored these possibilities for bone regeneration in the laboratory. One reason for this is that fabrication of the FKS scaffolds, such as by 3D printing, is challenged by a lack of algorithms to model and slice this topology for use by low-cost biomaterial printers. This paper presents an open-source software algorithm that we developed to create 3D-printable FKS and gyroid scaffold cubes, with a framework that can accept any continuous differentiable implicit function. We also report on our successful 3D printing of hydroxyapatite FKS scaffolds using a low-cost method that combines robocasting with layer-wise photopolymerization. Dimensional accuracy, internal microstructure, and porosity characteristics are also presented, demonstrating promising potential for the 3D printing of TPMS ceramic scaffolds for bone regeneration.

Titanium Implant Alloy Modified by Electrochemically Deposited Functional Bioactive Calcium Phosphate Coatings

Calcium phosphate-based (CaP) bioceramic materials are widely used in the field of bone regeneration, both in orthopaedics and in dentistry, due to their good biocompatibility, osseointegration and osteoconduction. The formation of CaP coatings on high-strength implant materials such as titanium alloys combines the superior mechanical properties of metals with the osteoconductive properties of CaP materials. In this work, the electrochemically assisted deposition of CaP coatings on the titanium alloy, TiAlNb, which is commonly used commercially as an implant material in orthopaedic devices, was examined. The barrier properties (electronic properties) of unmodified and CaP-modified titanium alloy were tested in situ in a simulated physiological solution, Hanks’ solution, under in vitro conditions of real implant applications using electrochemical impedance spectroscopy (EIS). The morphology and microstructure of the obtained CaP deposit were characterised by scanning electron microscopy (SEM) and chemical composition was assessed by energy dispersive X-ray spectroscopy (EDS) and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). The aim was to investigate the effect of calcium phosphate CaP coating on the corrosion resistance of the titanium TiAlNb alloy and to understand better the deposition process in the production of bioactive functional coatings on metallic implant materials.

Enhancing osteoinduction and bone regeneration of biphasic calcium phosphate scaffold thought modulating the balance between pro-osteogenesis and anti-osteoclastogenesis by zinc doping

Biphasic calcium phosphate (BCP) is a promising bone regeneration material with an adjustable degradation rate, and ions doping is an effective method to improve its bone repair effect. However, few studies have focused on the role of ions doping-mediated osteogenesis and osteoclastogenesis balance in bone regeneration. In order to improve the bone repair effect of BCP and emphasize the role of osteogenesis and osteoclastogenesis balance regulated by ions doping to promote bone regeneration. Here, zinc (Zn), an essential trace element with pro-osteogenesis and anti-osteoclastogenesis, was dopped into BCP scaffolds, and its effects on the physicochemical properties, in vitro cytological responses, in vivo osteoinduction, and bone defect regeneration of BCP were systematically investigated. Results showed that Zn was successfully introduced into the crystal lattice of BCP. The differentiation of both osteoblasts and osteoclasts showed a doping content-dependent behavior. By increasing the doping content (0–5 mol.%), the anti-osteoclastogenesis effect of BCP gradually increased, while its pro-osteogenesis performance first increased and then decreased. ThoughBCP with a doping content of 5 mol.% could promote osteogenic differentiation of stem cells and reduced fibrous capsule encapsulation, it could not enhance ectopic bone formation or bone regeneration due to its excessive anti-osteoclastogenesis. BCP with a doping content of 2.5 mol.% remarkably enhanced the osteoinduction activity and accelerated new bone formation, which were associated with its highest pro-osteogenesis and appropriate anti-osteoclastogenesis activity. This study highlights on regulating the balance between pro-osteogenesis and anti-osteoclastogenesis by Zn doping and paves the way for the development of a more osteoinductive calcium phosphate-based material for bone regeneration.

An Overview of Antibacterial Dental Restorative Materials

Antibacterial dental restorative materials (ADRM) have been developed to prevent or treat dental caries and other infections. Glass ionomer cements (GICs), composite resins, calcium hydroxide-based materials, mineral trioxide aggregate (MTA), bioactive glasses, silver-containing materials, quaternary ammonium compounds (QACs), chlorhexidine, nanoparticles, and photodynamic therapy (PDT) are common types of ADRMs. They have antibacterial properties due to the release of fluoride ions, QACs, silver nanoparticles, calcium and hydroxyl ions. ADRMs can prevent tooth decay, promote healing of pulp tissue and regenerate damaged tissues. Researchers are exploring new agents like nanoparticles and antimicrobial peptides to improve the antibacterial properties of ADRMs. PDT is a promising technology for improving the antibacterial properties of dental restorative materials. Antibacterial bioactive dental materials like bioactive glasses, calcium phosphate-based materials, hydroxyapatite-based materials, antibacterial peptides, and silver-containing materials have been developed to provide an additional layer of protection against infection and improve the longevity of dental restorations.

Mercury determination in bioresorbable calcium phosphate using a new electrothermal vaporization system coupled to ICP-MS

A new ETV system coupled to ICP-MS was developed to determine Hg at the ultra-trace level in bioresorbable calcium phosphate-based ceramic materials.

High strength bioinspired calcium phosphate-based material for bone repair applications

Owing to the increasing demand for bone repair strategies, several biomaterials have been developed. Among the materials available for this purpose, hydroxyapatite stands out for its osteoinduction capacity, since it possesses a chemical composition similar to that of inorganic bone constituents. In comparison to bones, the mechanical properties of substitute structures incorporating hydroxyapatite still remain a great challenge for scientists. This study thus presents the synthesis of hydroxyapatite incorporated with a natural bioceramic and a metallic phase of excellent biocompatibility to obtain dense biomaterials with improved mechanical strength. The mechanical responses of the synthesized biomaterials are presented and discussed. The results obtained indicate that the hydroxyapatite-natural ceramic systems fulfils the general mechanical property requirements for some bone repair applications. Separately, the synthesis of titanium-based systems was shown to be much more challenging, but promising. Therefore, recommendations for suppressing the issues with the metal-ceramic interfacial bonding strength were provided. • A simple method of synthesising hydroxyapatite composites for biomedical applications is presented. • Titanium-reinforced composites with calcium phosphate content close to natural bone were developed. • Waste seashells were used for extraction and recovery of valuable calcium oxide compounds. • Hydroxyapatite-based calcium oxide composites with high mechanical performance were synthesised.

Surgical Bone Adhesives with Potential Maxillofacial Applications A Systematic Review

The reduction and stabilisation of fractured bone fragments have always been a challenging task for thesurgeon. A micro-platesystem for maxillofacial fracture treatment provides excellent results. However, plates and screws are difficult toadapt to the thin bone, and small fragments often lead to the weakening of bone causing secondary fractures. Surgical bone adhesives promise as a viable alternative for issues with micro-plates, but a lotremains desired for successful usefor clinical application. The present systematic review aims to identify the bone adhesive materials available at various stages in animal or human models in the last decade and enumerate their characteristics for potential use in non-load bearing maxillofacial fractures. PubMed electronic database searched using a combination of keywords to identify English language articles between January 2011 and December 2020 yielded a total of 1204 records, of which 15 were included for final review after applying PRISMA guidelines. Cyanoacrylate was the commonly used adhesive material followed by fibrin glue and calcium phosphate-based materials. Although encouraging, results with each material still lack human randomised control trials thus presenting inconclusive evidence. Studies on these lines are suggested along with the development of newer materials to overcome the shortcomings in the currently available systems.

Calcium-magnesium phosphate biphasic microspheres with nutrient microchannels promote angiogenesis and osteogenic differentiation

Vascularisation and mineralisation are indispensable conditions for bone repair materials. The introduction of magnesium ions into calcium phosphate-based materials can give them angiogenic and mineralising capabilities. However, the optimum calcium to magnesium ratio has yet to be determined. Microspheres have received much attention from researchers due to their flexibility, non-agglomeration and other advantages. We prepared calcium-magnesium phosphate biphasic microspheres (CMBS) using the water-in-oil emulsion cross-linking method to achieve osteogenic differentiation and vascularisation. The simultaneous use of the sacrificial template method and heat treatment endow the microspheres with a rich micro-pore structure. In addition, we investigated the compounding ratio of calcium phosphate to magnesium phosphate and determined the optimal compounding ratio (Ca/Mg = 3/1–1/1) for this material. The prepared microspheres promoted the attachment, proliferation and directed differentiation of bone marrow mesenchymal stromal cells (BMSCs) and human umbilical vein cells (HUVECs). CMBS-I (Ca/Mg = 3/1) and CMBS-II (Ca/Mg = 1/1) microspheres showed the best promotion effect among all groups. These microspheres were implanted under the skin of Sprague- Dawley (SD) rats, and the composite microspheres significantly induced vascular regeneration compared to pure phase microspheres.

Tunable Behavior in Solution of Amorphous Calcium Ortho/Pyrophosphate Materials: An Acellular In Vitro Study.

Amorphous calcium phosphate-based materials are of major interest in the field of bone substitution. Very recently, the low-temperature synthesis of a new family of amorphous calcium phosphate containing both orthophosphate and pyrophosphate ions in controlled proportions has been reported. Despite their interest, especially due to the biochemical role and the hydrolysis of pyrophosphate occurring in vivo, the behavior of such materials when interacting with aqueous media has never been described. Consequently, we herein report the in vitro acellular evolution of three compositions of mixed calcium ortho- and pyrophosphate amorphous materials including a different orthophosphate proportion. As a first step to assess the physicochemical reactivity of these amorphous materials, they were tested in two different media at 37 °C, acidified water and simulated body fluid solution, from 1 h up to 15 days. The results demonstrated that they were quite stable and that they progressively released part of their constitutive ions, highlighting their potential for controlled delivery of bioactive ions (calcium, orthophosphate, and pyrophosphate ions). In addition to these properties, we showed that the material with the highest ortho/(ortho + pyro) phosphate ratio started to crystallize into nanocrystalline apatite analogous to bone mineral within 2 days or 2 weeks depending on the medium. For the other material compositions, no layer of apatite was detected at their surface with SBF testing despite the favorable supersaturation indexes, crystallization being probably inhibited by pyrophosphate ions released in the medium. This varying apatite-forming ability emphasizes the key role of the ortho/(ortho + pyro) phosphate ratio of these materials in their in vitro reactivity and bioactivity, which paves the way for the development of this promising family of amorphous calcium phosphate materials with tunable physicochemical and biological properties.

Novel β-TCP/HA biphasic calcium phosphate microspheres with porous surface structure prepared via a calcium carbonate template

Calcium phosphate-based materials have been considered and widely developed as a promising candidate for bone repair and regeneration. With an aim to allow a better balance between resorption and degradation, novel beta-tricalcium and hydroxyapatite (β-TCP/HA) biphasic calcium phosphate (BCP) microspheres with different surface topographies were successfully prepared in this study. Results revealed that the surface topography structure of prepared BCP microspheres could be adjusted by tuning phosphoric acid concentrations and pH values. In vitro cytocompatibility has also been evaluated by CCK-8 and live/dead staining. Moreover, the potential applications of the obtained BCP microspheres as drug delivery were investigated by using the doxycycline as a model drug. All the results have demonstrated that utilizing the spherical calcium carbonate as a hard template is an effective strategy for synthesizing advanced β-TCP/HA BCP microspheres with controllable surface topography, which holds tremendous promise for bone regeneration and drug delivery applications.

Assessment of Streptococcus mutans biofilm formation on calcium phosphate ceramics: The role of crystalline composition and microstructure.

Streptococcus mutans is one of the bacteria that initiates the colonization of the pellicle at the tooth surface. It forms a plaque, together with other bacteria, which gradually dissolves the pellicle and leaves the tooth surface unprotected against the acidic oral environment. Calcium phosphate ceramics are excellent synthetic materials for the study of biofilm formation in dentistry because they are comparable to teeth in chemical composition and structure. Calcium phosphates can be processed to achieve a variety of crystalline compounds with biologically relevant ionic substitutions and structures that allow study of the effect of the surface chemistry and the topography independently. In this article, we describe the preparation and characterization of three types of calcium phosphate-based materials as a suitable surface for the formation of the S. mutans biofilm: beta-tricalcium phosphate (β-TCP); sintered hydroxyapatite (SHA); and calcium-deficient hydroxyapatite (CDHA). The densest biofilms were formed on the surfaces of SHA and CDHA, with no significant differences due to the stoichiometry or microstructure. In contrast, β-TCP showed a lower susceptibility to S. mutans biofilm formation, suggesting that the crystalline structure is the controlling parameter. Subsequently, SHA was selected to develop a dental biofilm model that allowed study of S. mutans biofilm susceptibility to chlorhexidine and ethanol.

Calcium phosphate-based materials regulate osteoclast-mediated osseointegration

Calcium phosphate-based materials (CaP) have been widely used as bone graft substitutes with a decent osseointegration. However, the mechanism whereby cells function and repair the bone defect in CaP micro-environment is still elusive. The aim of this study is to find the mechanism how osteoclast behaviors mediate bone healing with CaP scaffolds. Recent reports show that behaviors of osteoclast are closely related with osteogenesis, thus we make a hypothesis that active osteoclast behaviors induced by CaP facilitate bone healing. Here, we found a new mechanism that CaP can regulate osteoclast-mediated osseointegration. Calcium phosphate cement (CPC) is selected as a representative CaP. We demonstrate that the osteoclast-mediated osseointegration can be strongly modulated by the stimulation with CaP. An appropriate Ca/P ratio in CaP can effectively promote the RANKL-RANK binding and evoke more activated NF-κB signaling transduction, which results in vigorous osteoclast differentiation. We observe significant improvement of bone healing in vivo, owing to the active coupling effect of osteoclasts. What is more noteworthy is that the phosphate ions released from CaP can be a pivotal role regulating osteoclast activity by changing Ca/P ratio readily in materials. These studies suggest the potential of harnessing osteoclast-mediated osteogenesis in order to develop a materials-manipulated approach for improving osseointegration.

Mechanism of apatite formation on a poorly crystallized calcium phosphate in a simulated body fluid (SBF) at 37 °C

Calcium phosphate-based bioactive materials have recently attracted considerable attention. In particular, poorly crystalline apatites (PCA) are successfully used for bone repair and regeneration, enhancing the osteointegration and osteoconduction properties. Our study aims to better understand the mechanism of apatite formation on the poorly crystallized apatite powders. For this purpose, two PCA samples were synthesized in the same conditions while varying only the maturation time.The most noticeable difference between both samples is that the immature specimen (PCA2h) was richer in both water and HPO42− labile species than the mature specimen (PCA2m). Besides, it has a higher surface area and more negatively charged surface. Both PCA samples were soaked in a simulated body fluid (SBF) for different periods of time at 37 °C, leading to the neoformation of bone-like apatite layer on their surfaces due to their bioactivity. The surface of all samples was investigated using scanning electron microscopy (SEM) coupled with energy-dispersive X-ray (EDX) spectroscopy, zeta-potential measurements and BET analysis. FTIR spectroscopy, XRD, and TG-DTA were used to characterize bulk samples. Thermodynamic calculations of CaP precipitation were also performed. Experimental and theoretical data showed that the bone-like apatite formation mechanism on both samples undergoes by three stages. Only on the PCA2h, did a fast precipitation of positively Ca-rich amorphous phase (ACP) occur at a first time (prenucleation stage). It is converted into Ca-poor ACP by uptaking anions from surrounding media, to promote the formation of apatite nuclei during the second stage (nucleation stage). Then, nascent apatite crystals grew into bone like-apatite coating by poorly crystallized BCO3-apatite which is the most thermodynamically stable CaP phase in SBF (growing and maturation stage). While the bone like-apatite formation process on the mature PCA particles include similar events without Ca-rich ACP deposit. Thus, the formation of the Ca-poor ACP starts immediately at the beginning of soaking (at the 1st stage), followed by apatite nucleation (2nd stage), promoting the growth and maturation of BCO3-apatite crystals (3rd stage). Our results highlight the fact that in the waterlogged conditions of the hydrated shells surrounding the immature PCA nanocrystals, a high density of labile orthophosphate anions leads enriches the PCA-liquid solution interface in Ca2+ ions, momentarily stabilizing them into a positively charged amorphous complex likely to be strongly solvated. Then, this interface becomes more attractive for free orthophosphate anions, enhancing the bioactivity to improve osteointegration. The composition of the hydrated shells coating of the biomimetic apatite crystal in both labile species and hydration water seems to govern their bioactivity via surface charge potential and hydrophilic capacity. These data allow a better understanding of the bioactive behaviour of biomaterials involving biomimetic PCA phases for tissue engineering.