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In the biomedical fields of bone regenerative therapy, the immobilization of proteins on the bioceramic particles to maintain their highly ordered structures is significantly important. In this review, we comprehensively discussed the importance of the specific surface layer, which can be called “non-apatitic layer”, affecting the immobilization of proteins on particles such as hydroxyapatite and amorphous silica. It was suggested that the water molecules and ions contained in the non-apatitic layer can determine and control the protein immobilization states. In amorphous silica particles, the direct interactions between proteins and silanol groups make it difficult to immobilize the proteins and maintain their highly ordered structures. Thus, the importance of the formation of a surface layer consisting of water molecules and ions (i.e., a non-apatitic layer) on the particle surfaces for immobilizing proteins and maintaining their highly ordered structures was suggested and described. In particular, chlorine-containing amorphous silica particles were also described, which can effectively form the surface layer of protein immobilization carriers. The design of the bio-interactive and bio-compatible surfaces for protein immobilization while maintaining the highly ordered structures will improve cell adhesion and tissue formation, thereby contributing to the construction of social infrastructures to support super-aged society.

Amorphous silica particles (ASPs) have been reported to exhibit bioactive properties and are becoming the focus of attention as bioceramics. However, their interactions with proteins in living organisms remain to be understood and need to be investigated in order to achieve wider applications. Our research group found that chlorine (Cl)-containing ASPs are useful for protein immobilization. Photofunctional dyes (fluorescein (FS−), methylene blue (MB+)) that have the carboxy and amino groups as the main functional groups were immobilized on the Cl-containing ASPs via the mechanochemical method as the model molecule and their spectral properties were used to investigate and discuss the organic/inorganic interfacial bonding states. In FS−, the oxygen atoms of the carboxy groups in the molecule were immobilized by the hydrogen bonds with the silanol groups on the ASPs surfaces, indicating that there is an optimum Cl content for the immobilization as the monomer state. In the case of MB+, as the Cl concentration in the ASPs increases, the immobilization via the electrostatic interactions between the Cl in the ASPs and the terminal dimethylamino group, and the hydrogen bonding between the N atoms of the MB+ hetero ring and the particle silanol group were enhanced. These results mainly suggest that the protein adsorption system occurs through the hydrogen bonding between the carboxy groups of the protein and the silanol groups on the particles and via electrostatic interactions between the amino groups of the protein and the dissociated silanol groups and the contained Cl at the particles. Thus, the spectral characterization using dyes as probes is expected to predict the protein interactions with the amorphous silica particles.

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 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.

Theranostics (bifunction of therapeutics and diagnostics) has attracted increasing attention due to its efficiency that can reduce the physical and financial burden on patients. One of the promising materials for theranostics is calcium phosphate (CP) and it is biocompatible and can be functionalized not only with drug molecules but also with rare earth ions to show photoluminescence that is necessary for the diagnostic purpose. Such the CP-based hybrids are formed in vivo by interacting between functional groups of organic molecules and inorganic ions. It is of great importance to elucidate the interaction of CP with the photofunctional species and the drug molecules to clarify the relationship between the existing state and function. Well-designed photofunctional CPs will contribute to biomedical fields as highly-functional ormultifunctional theranostic materials at the nanoscales. In this review, we describe the hybridization between CPs and heterogeneous species, mainly focusing on europium(III) ion and methylene blue molecule as the representative photofunctional species for theranostics applications.

The highly-oriented structures in biological tissues play an important role in determining the functions of the tissues. In order to artificially fabricate oriented nanostructures similar to biological tissues, it is necessary to understand the oriented mechanism and invent the techniques for controlling the oriented structure of nanobiomaterials. In this review, the oriented structures in biological tissues were reviewed and the techniques for producing highly-oriented nanobiomaterials by imitating the oriented organic/inorganic nanocomposite mechanism of the biological tissues were summarized. In particular, we introduce a fabrication technology for the highly-oriented structure of nanobiomaterials on the surface of a rubbed polyimide film that has physicochemical anisotropy in order to further form the highly-oriented organic/inorganic nanocomposite structures based on interface interaction. This is an effective technology to fabricate one-directional nanobiomaterials by a biomimetic process, indicating the potential for wide application in the biomedical field.

The mineralization process of the osseous layer, which is highly calcified in vivo, was successfully imitated by the immersion process of the decalcified fish scales in simplified simulated body fluid (SSBF). An alkali treatment was used to modify the native collagen in the decalcified Tilapia fish scale. After the alkali treatment, the mineralization was facilitated in SSBF. The XRD patterns and SEM-EDS observation results demonstrated that the externally-mineralized layers by the immersion process were highly similar to the osseous layer containing lower-crystalline hydroxyapatite, suggesting that the simple biomimetic precipitation process was developed.

Biological hydroxyapatite (HA) contains the different minor ions which favour its bio-reactivity in vivo. In this study, the preparation of HA particles containing both silicate and carbonate ions under the presence of sodium silicate was investigated, and the physicochemical properties were evaluated according to the contents and states of silicate and carbonate ions. The increment in the silicate ion reduced the crystallinity and expanded the crystalline size along with a-axis. Solid-state 29Si–NMR spectra indicated the increase in the adsorption of oligomeric silicate species on the HA particle surfaces in addition to the substitution state of silicate ions, suggesting the occurrence of the surface coating of silicates on the surfaces. The possible states of carbonate and silicate ions at the HA surfaces will provide the bioactivity.

For the development of next-generation protein-based biosensor surfaces, it is important to understand how functional proteins, such as fibrinogen (FBG), interact with polar substrate surfaces in order to prepare highly sensitive points of medical care diagnostics. FBG, which is a fibrous protein with an extracellular matrix, has both positively and negatively charged regions on its 3-dimensional surface, which makes interpreting how it effectively binds to polarized surfaces challenging. In this study, single-crystal LiNbO3 (LNO) substrates that have surface charges were used to investigate the adsorption of FBG protruding polar fragments on the positively and negatively charged LNO surfaces. We performed a combination of experiments and multi-scale molecular modeling to understand the binding of FBG in vacuum and water-solvated surfaces of LNO. XPS measurements showed that the FBG adsorption on LNO increased with increment in solution concentration on surfaces independent of charges. Multi-scale molecular modeling employing Quantum Mechanics, Monte Carlo, and Molecular Mechanics addressed the phenomenon of FBG fragment bonding on LNO surfaces. The binding simulation validated the experimental observation using zeta potential measurements which showed presence of solvated medium influenced the adsorption phenomenon due to the negative surface potential.