Hydroxyapatite (HA) particle, which is an inorganic component of biological hard tissues, is being applied as a bioceramic for biotechnology and medicine fields. However, early bone formation is difficult in the implantation of well-known stoichiometric HA into our body. To solve this problem, it is important to control the shapes and chemical compositions of the physicochemical properties of HA to be functionalized as the state similar to the biogenic bone. In this study, the physicochemical properties of the HA particles synthesized in the presence of tetraethoxysilane (TEOS) (SiHA particles) were evaluated and investigated. In particular, the surface layers of the SiHA particles were successfully controlled by adding silicate and carbonate ions in the synthetic, which would be involved in the bone formation process, and their elusive reaction behavior with phosphate-buffered saline (PBS) was also evaluated. The results showed that the ions in the SiHA particles increased with the increase in the added TEOS concentration, and the silica oligomer was also formed on the surfaces. The ions were present not only in the HA structures but also on the surface layers, indicating the formation of the non-apatitic layer containing the hydrated phosphate and calcium ions. The change in state of the particles with the immersion in PBS was evaluated, the carbonate ions eluted from the surface layer into PBS, and the free water component in the hydration layer increased with the immersion time in PBS. Therefore, we successfully synthesized the HA particles containing silicate and carbonate ions, suggesting the important state of the surface layer consisting of the characteristic non-apatitic layers. It was found that the ions in the surface layers can react with PBS and leach out, weakening the interaction of hydrated water molecules on the particle surfaces to increase the free water component in the surface layer.

In this review, the current status of the influence of added ions (i.e., SiO44−, CO32−, etc.) and surface states (i.e., hydrated and non-apatite layers) on the biocompatibility nature of hydroxyapatite (HA, Ca10(PO4)6(OH)2) is discussed. It is well known that HA is a type of calcium phosphate with high biocompatibility that is present in biological hard tissues such as bones and enamel. This biomedical material has been extensively studied due to its osteogenic properties. The chemical composition and crystalline structure of HA change depending on the synthetic method and the addition of other ions, thereby affecting the surface properties related to biocompatibility. This review illustrates the structural and surface properties of HA substituted with ions such as silicate, carbonate, and other elemental ions. The importance of the surface characteristics of HA and its components, the hydration layers, and the non-apatite layers for the effective control of biomedical function, as well as their relationship at the interface to improve biocompatibility, has been highlighted. Since the interfacial properties will affect protein adsorption and cell adhesion, the analysis of their properties may provide ideas for effective bone formation and regeneration mechanisms.

A systematic study of the real-time initial adhesion properties of fibroblasts on a fetal bovine serum-preadsorbed hydroxyapatite surface was successfully realized using a quartz crystal microbalance with dissipation analysis.

Titania and silica have been recognized as potential drug delivery system (DDS) carriers. For this application, controllable biocompatibility and the suppression of the initial burst are required, which can be provided by a calcium phosphate (CP) coating. However, it is difficult to control the morphology of a CP coating on the surface of carrier particles owing to the homogeneous nucleation of CP. In this study, we report the development of a CP-coating method that homogeneously corresponds to the shapes of silica–titania (SiTi) porous nanoparticles. We also demonstrate that controlled surface roughness of CP coatings could be achieved in SBF using SiTi nanoparticles with a well-defined spherical shape, a uniform size, and a tunable nanoporous structure. The precipitation of CP was performed on mono-dispersed porous SiTi nanoparticles with different Si/Ti molar ratios and pore sizes. The pore size distribution was found to significantly affect the CP coating in SBF immersion; the surfaces of the nanoparticles with bimodal pore sizes of 0.7 and 1.1–1.2 nm became rough after CP precipitation, while those with a unimodal pore size of 0.7 nm remained smooth, indicating that these two pore sizes serve as different nucleation sites that lead to different surface morphologies.

In this review, the current status and issues of bone defect sites in our body were explained based on the examples of the conventional hydroxyapatite (HA), and the necessity of regenerative functions in addition to bone defect sites for the biomedical applications was proposed. The characteristics and properties of HA substituted with the heterogeneous ions such as silicate, carbonate and other elemental ions were explained. For the effective control of the biomedical function, the characteristics and possibilities of the surface layer formed on HA and its components, the hydrated layer and the non-HA layer were proposed, and their relationship for improving the biocompatibility was highlighted.