Bone defects and periodontal disease are pathological conditions that may become neglected diseases if not treated properly. Hydroxyapatite (HA), along with tricalcium phosphate and bioglass ceramic, is a biomaterial widely applied to orthopedic and dental uses. The in vivo performance of HA is determined by the interaction between HA particles with bone cells, particularly the bone mineralizing cells osteoblasts. It has been reported that HA-induced osteoblastic differentiation by increasing the expression of osteogenic transcription factors. However, the pathway involved and the events that occur in the cell membrane have not been well understood and remain controversial. Advances in gene editing and the discovery of pharmacologic inhibitors assist researchers to better understand osteoblastic differentiation. This review summarizes the involvement of extracellular signal-regulated kinase (ERK), p38, Wnt, and bone morphogenetic protein 2 (BMP2) in osteoblastic cellular regulation induced by HA. These advances enhance the current understanding of the molecular mechanism of HA as a biomaterial. Moreover, they provide a better strategy for the design of HA to be utilized in bone engineering.

Submicron hydroxyapatite has been reported to have beneficial effects in bone tissue engineering. This study aimed to fabricate submicron-scale bovine hydroxyapatite (BHA) using the high-energy dry ball milling method. Bovine cortical bone was pretreated and calcined to produce BHA powder scaled in microns. BHA was used to fabricate submicron BHA with milling treatment for 3, 6, and 9 h and was characterized by using dynamic light scattering, scanning electron microscope connected with energy dispersive X-Ray spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffractometry to obtain its particle size, calcium-to-phosphorus (Ca/P) ratio, functional chemical group, and XRD peaks and crystallinity. Results showed that the particle size of BHA had a wide distribution range, with peaks from ~5 to ~10 µm. Milling treatment for 3, 6, and 9 h successfully gradually reduced the particle size of BHA to a submicron scale. The milled BHA’s hydrodynamic size was significantly smaller compared to unmilled BHA. Milling treatment reduced the crystallinity of BHA. However, the treatment did not affect other characteristics; unmilled and milled BHA was shaped hexagonally, had carbonate and phosphate substitution groups, and the Ca/P ratio ranged from 1.48 to 1.68. In conclusion, the fabrication of submicron-scale BHA was successfully conducted using a high-energy dry ball milling method. The milling treatment did not affect the natural characteristics of BHA. Thus, the submicron-scale BHA may be potentially useful as a biomaterial for bone grafts.

Curcumin is one of the most popular medicines due to its various pharmacological properties. Nonetheless, curcumin has low bioavailability, insoluble in water, and aggregates easily. This can be overcome by formulating curcumin into nanoemulsion. One of the methods to produce nanoemulsion is wet-ball milling. The aims of this study are, firstly, to determine the optimum milling time to produce curcumin nanoemulsion in the Virgin Coconut Oil (VCO)-Tween 80 system, and secondly to determine the curcumin loading capacity and efficiency of encapsulation. The optimum milling time is evaluated based on the particle size, polydispersity index, and nanoemulsion stability. Curcumin loading capacity and efficiency of encapsulation is analyzed based on the maximum mass of curcumin added in the system which still can maintain particle size in the range of nanoemulsion (under 1000 nm) and the amount of curcumin entrapped in the droplets. Curcumin nanoemulsion was made by the combination of 1 mg curcumin powder, 200 µl VCO as oil phase, 60 µl Tween 80 as surfactant, and 5 ml distilled water as the dispersion medium. Meanwhile, the milling time is varied at 1, 4, 8 and 24 hours. Particle size and polydispersity index are measured using Particle Size Analyzer using Dynamic Light Scattering technique while encapsulation efficiency is calculated based on the curcumin absorption using UV-Vis spectrophotometer. The results show that curcumin nanoemulsion system milled for 24 hours produce smallest particle size (160 nm), lowest polydispersity index (0.176), and stable during 30 days in the storage at room temperature (25 °C) and refrigerator temperature (4 °C). The maximum of curcumin that can be added in the nanoemulsion and produce particle size below 500 nm is 300 mg. Encapsulation efficiency obtained is 78.13 % of the total curcumin in the nanoemulsion system. In summary, the current work has demonstrated the successful incorporation of curcumin into oil in water (O/W) nanoemulsion particles with small particle size, low index polydispersity, good physical stability, and high encapsulation efficiency.