# Octacalcium Phosphate Bone Substitute (Bontree(r)): From Basic Research to Clinical Case Study
###### Abstract  
Bone grafts used in alveolar bone regeneration can be categorized into autografts, allografts, xenografts, and synthetic bones, depending on their origin. The purpose of this study was to evaluate the effect of a commercialized octacalcium phosphate (OCP)-based synthetic bone substitute material (Bontree(r)) in vitro, in vivo, and in clinical cases. Material characterization of Bontree(r) granules (0.5 mm and 1.0 mm) using scanning electron microscopy and X-ray diffraction showed that both 0.5 mm and 1.0 mm Bontree(r) granules were uniformly composed mainly of OCP. The receptor activator of NF-xB ligand (RANKL) and alkaline phosphatase (ALP) activities of MG63 cells were assessed and used to compare Bontree(r) with a commercial biphasic calcium phosphate ceramic (MBC+TM). Compared with MBC+TM, Bontree(r) suppressed RANKL and increased ALP activity. A rabbit tibia model used to examine the effects of granule size of Bontree(r) grafts showed that 1.0 mm Bontree(r) granules had a higher new bone formation ability than 0.5 mm Bontree(r) granules. Three clinical cases using Bontree(r) for ridge or sinus augmentation are described. All eight implants in the three patients showed a 100% success rate after 1 year of functional loading. This basic research and clinical application demonstrated the safety and efficacy of Bontree(r) for bone regeneration. b 27 August 2021  
Octacalcium Phosphate Bone Substitute (Bontree(r)): From Basic Research to Clinical Case Study  
[PERSON], [PERSON], [PERSON], [PERSON] Octacalcium Phosphulate Bone Substitute  
(Bontree(r)): From Basic Research to Clinical Case Study  
[PERSON], [PERSON], [PERSON], [PERSON]. defects at the donor site [5]. Allografts do not require surgery at the donor site and have osteoinduction and osteoconduction capabilities, but antigenicity- and infection-related problems may arise. In addition, new bone formation depends on the condition of the donor, which is a disadvantage [6]. Deproteinized bovine bone mineral (DBBM) is the most commonly used xenograft material in clinical practice. It has a calcium/phosphorus ratio similar to that of human bone, and its excellent osteoconductivity has been proven. However, xenografts have only osteoconductive ability and high absorption resistance; therefore, new bone formation is slower than that associated with autografts [7]. Synthetic bone graft materials can be mass-produced, their properties can be controlled, and there is no risk of cross-infection, although there are limitations such as low biodegradability depending on the material. Ceramics, tricalcium phosphate (TCP), and hydroxyapatite (HA) are used as synthetic bone materials. Several studies have been conducted on HA and \(\beta\)-TCP, which are calcium phosphate-based biomaterials [8]. Recently, octacalcium phosphate (OCP, Ca\({}_{8}\)H\({}_{2}\)[PO\({}_{4}\)]\({}_{6}\).5H\({}_{2}\)O) was developed as a new synthetic bone substitute [9]. OCP is irreversibly converted to sustainable biological apatite under physiological conditions because OCP is a direct precursor of biological apatite [10]. OCP has been proven to be effective for new bone formation because of its high osteogenic capability and rapid bioavailability [11]. However, the sintering process changes the original crystal structure of OCP, and it cannot be formed into larger solid masses by sintering. In other words, OCP is generally fragile and difficult to develop as a synthetic bone substitute [12]. Due to these limitations, studies aimed at the commercialization of OCP-based bone substitutes have focused on coating OCP on DBBM [13] or mixing it with collagen [9; 12; 14]. However, a new synthesis method that does not require sintering was recently developed to mass-produce high-purity OCP with improved physical properties.