As alternatives to autografts, allografts, and xenografts, calcium phosphate (CaP)-based bone-defect-filling materials (e.g., deproteinized bovine bone (DBB, Bio-Oss^®)) are widely used to repair large-volume bone defects (LVBDs) in clinic. However, most of these materials show a very low degradability due to a sintering process in their production. In this study, we synthesized a novel type of granules—biomimetically precipitated nanocrystalline calcium phosphate (BpNcCaP) by developing our previous biomimetic protocol. We evaluated the cytotoxicity of BpNcCaP by assessing the viability of L929 mouse fibroblasts using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. To characterize the physicochemical properties of the novel BpNcCaP granules, we first compared the morphology and composition of BpNcCaP with those of Bio-Oss^® using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). We further compared the surface area, pore size distribution, hydrophilicity behavior, and hardness of BpNcCaP with those of Bio-Oss^® granules using specific surface area, contact angle, and Vickers hardness as parameters, respectively. BpNcCaP showed no obvious cytotoxicity. In-vitro characterization data showed that BpNcCaP and Bio-Oss^® granules were both comprised of nanocrystalline hydroxyapatite (HAp). The Ca/P ratios of BpNcCaP and Bio-Oss^® calculated from the EDS results were 1.34 and 1.66, respectively. Hence, BpNcCaP and Bio-Oss^® were Ca-deficient HAp. Compared with Bio-Oss^®, synthetic BpNcCaP had better hydrophilicity, higher specific surface area, lower crystallinity, and hardness. These data suggested a good performance of BpNcCaP granules in clinical applications.

Nanocrystalline hydroxyapatite has been extensively used for biomedical field, such as drug carrier, antitumor agent, surface coating, and bone-regenerating material. The wet chemical method is one of the most commonly used methods in the synthesis of nanosized hydroxyapatite due to its relatively low costs and more customizable control of the final product. Herein, we updated the most recent advances in artificial nano-hydroxyapatite prepared from biomimetic precipitation throughout context. Furthermore, micron-sized particles and macro-sized scaffolds made of nano-hydroxyapatite deposition are introduced. Their outstanding physicochemical properties and potential clinical application are highlighted. This article reviews the latest progress on preparing biomimetic nano-hydroxyapatite and provides inspiration to promote new breakthrough in regenerative therapy and clinical translation.