Surface functionalization of hydroxyapatite nanoparticles for biomedical applications.

This review completely covers the various aspects of hydroxyapatite (HAp) nanoparticles and their role in different biological situations, and provides the surface and interface contents on (i) hydroxyapatite nanoparticles and their hybridization with organic molecules, (ii) surface designing of hydroxyapatite nanoparticles to provide their biocompatibility and photofunction, and (iii) coating technology of hydroxyapatite nanoparticles. In particular, we summarized how the HAp nanoparticles interact with the different ions and molecules and highlighted the potential for hybridization between HAp nanoparticles and organic molecules, which is driven by the interactions of the HAp nanoparticle surface ions with several functional groups of biological molecules. In addition, we highlighted the studies focusing on the interfacial interactions between the HAp nanoparticles and proteins for exploring the enhanced biocompatibility. Such studies focus on how these interactions affect the hydration layers and protein adsorption. However, the hydration layer state involves diverse molecular interactions that can alter the shape of the adsorbed proteins, thereby affecting cell adhesion and spreading on the surfaces. We also summarized the relationship between the surface properties of the HAp nanoparticles and the hydration layer. Furthermore, we spotlighted the cytocompatible photoluminescent probes that can be developed by designing HAp/organic nanohybrid structures. We then emphasized the importance of photofunctionalization in theranostics, which involves the integration of diagnostics and therapy based on the surface design of the HAp nanoparticles. Furthermore, the coating techniques using HAp nanoparticles and HAp nanoparticle/polymer composites were outlined for fusing base biomaterials with biological tissues. The advantages of HAp/biocompatible polymer composite coatings include the ability to effectively cover porous or irregularly shaped surfaces while controlling the thickness of the coating layer, and the addition of HAp nanoparticles to the polymer matrix improves the mechanical properties, increases the roughness, and forms the morphologies that mimic bone nanostructures. Therefore, the fundamental design of hydroxyapatite nanoparticles and their surfaces was suggested from various aspects for biomedical applications.

Investigation of Surface Layers on Biological and Synthetic Hydroxyapatites Based on Bone Mineralization Process.

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.

Drug Molecular Immobilization and Photofunctionalization of Calcium Phosphates for Exploring Theranostic Functions.

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.