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.

Osteomyelitis is an infectious disease which is also a major complication of bone defects. This study aims to determine the effect of bovine hydroxyapatite-gelatin-based bone implants with gentamicin as an antibiotic (BHA-GEL-GEN implant) on the regeneration of bone defects in vivo. The BHA-GEL-GEN and BHA-GEL implants were made by direct compression. In vivo study was carried out with Wistar rats. The rats were divided into three groups: negative control, BHA-GEL implant, and BHA-GEL-GEN implants. The defect model used was the burr hole defect model with diameter 2.2mm and 2mm deep. After 2, 7, 14, and 28 days, the rats were sacrificed. Bone integrity was carried out using X-ray radiography. Radiological examination was performed using haematoxylin and eosin (HE) staining and immunohistochemical techniques with anti-vascular endothelial growth factor (VEGF) and anti-alkaline phosphatase (ALP) antibodies. Based on the radiograph, the implanted group had accelerated bone growth in the defect area. Semiquantitative data from HE staining showed that the implanted group had accelerated migration of osteoclasts, osteoblasts, and osteocytes in the defect area. The immunoreactive score showed that the BHA-GEL-GEN group had higher VEGF expression compared to two other groups. The three groups did not provide a significant difference in ALP expression. In conclusion, the BHA-GEL-GEN implant causes accelerated bone defects repair by accelerating tissue vascularity and does not interfere with the bone remodeling process. Therefore, the BHA-GEL-GEN implant is potentially a biomedical material for osteomyelitis therapy.

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.

Bone grafts a commonly used therapeutic technique for the reconstruction and facilitation of bone regeneration due to fractures. BHA–GEL (bovine hydroxyapatite–gelatin) pellet implants have been shown to be able accelerate the process of bone repair by looking at the percentage of new bone, and the contact between the composite and bone. Based on these results, a study was conducted by placing BHA–GEL (9:1) pellet implants in rabbit femoral bone defects, accompanied by 500 mg oral supplement of BHA or calcium lactate to determine the effectiveness of addition supplements. The research model used was a burr hole defect model with a diameter of 4.2 mm in the cortical part of the rabbit femur. On the 7th, 14th and 28th days after treatment, a total of 48 New Zealand rabbits were divided into four groups, namely defect (control), implant, implant + oral BHA, and implant + oral calcium lactate. Animal tests were terminated and evaluated based on X-ray radiology results, Hematoxylin-Eosin staining, vascular endothelial growth Factor (VEGF), osteocalcin, and enzyme-linked immunosorbent assay (ELISA) for bone alkaline phosphatase (BALP) and calcium levels. From this research can be concluded that Oral BHA supplementation with BHA–GEL pellet implants showed faster healing of bone defects compared to oral calcium lactate with BHA–GEL pellet implants.

Over the past decade, the occurrence of bone defects has seen a notable rise. In both developed and developing nations, their prevalence tends to increase in parallel with population density and levels of physical activity. Various therapeutic approaches have been implemented to address bone fractures, focusing on preventing infections, promoting faster healing, and restoring normal bone function. Among these, bone grafting—a surgical technique involving the use of biomaterials—remains a widely utilized method for bone replacement. This review aims to identify biomaterials that have biocompatibility with bone, osteoinductive, and osteoconductive properties so that they can trigger good osteogenesis. This review is based on a compilation of publications from various databases related to factors affecting the process of bone ossification. This study also evaluates the characteristics of hydroxyapatite biomaterials that play a role in inducing osteogenesis. The phosphate/calcium ratio close to 1.67, porosity in the range of 40 to 60%, pore diameter of 200 to 900 nm, and crystallinity of 40 to 60% will help the osteogenesis to perform well. The results of this study highlight the advantages of hydroxyapatite in terms of its osteoconductive, osteoinductive, and osteointegrative properties, which can trigger osteogenesis.

Subchondral defects are often caused by trauma involving cartilage damage, leading to subsequent damage to the underlying bone, specifically the subchondral region. Bilayer scaffolds made from biomaterials, such as bovine hydroxyapatite, possess biocompatible and biodegradable properties that mimic the natural environmental conditions of target tissues so that they can support the formation of new tissues. On the other side, diclofenac as an anti‐inflammatory drug potentiates to inhibit the inflammatory excess regarding the damage. This study aims to study the effectiveness of diclofenac scaffold to rabbit joint defect model. The scaffold was implanted in the rabbit femoral trochlear bone hole, which had a diameter of 5 mm and a depth of 4 mm. After 28 days of intervention, the animals were examined using macroscopic evaluation, hematoxylin‐eosin (HE) staining, and immunohistochemistry (IHC) for type I collagen and type II collagen. Subsequently, the cartilage was evaluated using the International Cartilage Repair Society (ICRS) scoring system. The macroscopic ICRS scores were significantly higher (p < 0.05) in the bilayer scaffold implantation group compared to the monolayer scaffold and control groups. Histological ICRS scores were also significantly higher (p < 0.05) in the bilayer scaffold group compared to the control group. Type II collagen expression was higher (p < 0.05) in the bilayer scaffold group compared to the monolayer scaffold and control groups, although type I collagen expression was lower in comparison. In conclusion, this research suggests that the diclofenac‐loaded bilayer scaffold effectively enhances cartilage and subchondral bone regeneration.