Octacalcium phosphate (OCP) has attracted interest as an alloplastic bone graft due to its biomimetic crystal structure and bioactivity. This study evaluated the osteogenic and periodontal regenerative potential of OCP-based grafts through a multiphase approach including in vitro assays, in vivo validation in a dog model, and clinical application. OCP granules were physicochemically characterized and assessed using MG-63 cells for cytocompatibility, osteogenic differentiation, and gene expression. In vivo experiments were conducted in surgically created one-wall intrabony defects in dogs, followed by micro-computed tomography, histological, and histomorphometric analyses. OCP exhibited high porosity, a large surface area, and sustained release of calcium and phosphate ions. In vitro, OCP significantly enhanced osteogenic gene expression and mineralization. In vivo, OCP demonstrated greater new bone formation and regeneration area than defect-only controls at all time points and showed superior early-stage regeneration compared with biphasic calcium phosphate (BCP). Histomorphometric analysis confirmed favorable periodontal tissue regeneration, including the formation of cementum and the periodontal ligament. Clinical application of OCP-based grafts in guided tissue regeneration, ridge preservation, and sinus augmentation resulted in favorable outcomes without complications. Overall, these findings support OCP as an effective alloplastic graft material with translational potential for periodontal and implant-related regeneration.

Gelatin and collagen, known as natural proteins, have been used as additives to improve clinical usability and efficacy of synthetic bone substitutes. In particular, a method of adding natural proteins while synthesizing calcium phosphate minerals has been used to implement a composition similar to natural bone. In this study, octacalcium phosphate (OCP), a raw material for synthetic bone substitutes, was synthesized in a natural protein solution, and the effect of the added protein on the characteristics of OCP crystals was evaluated. OCP powders were prepared by the hydration of dicalcium phosphate dihydrate (DCPD) (CaHPO4.H2O) in a protein solution via a heterogeneous crystallization route. The properties of the synthesized OCP crystals were investigated to examine how they were influenced by the protein solution. Collagen and gelatin, used as protein molecules, expanded the a-axis lattice parameter (100) of OCP crystals by 3.1 % and 1.5 %, respectively, which is thought to be due to their incorporation into the hydration layer together with water molecules during OCP synthesis. In addition, the size of OCP crystals became smaller than that of OCP crystals synthesized in distilled water, which is thought to be due to the encapsulation oradsorption of OCP crystals by the added proteins. The incorporation or adsorption/encapsulation effects of proteins on OCP crystals varied depending on the type of protein. Gelatin showed greater changes than collagen in the crystal structure, particle shape, and thermal and hydrolytic stability of OCP powder due to protein incorporation into the hydration layer or adsorption on the surface of OCP crystal.

Octacalcium phosphate (OCP) is a precursor of biological apatite minerals that can be used in synthetic bone grafts. In this work, a new type of synthetic bone grafts was developed by adding water glass to OCP (W-OCP). The OCP phase is generally known to be thermodynamically unstable and rapidly hydrolyzes to apatite. However, X-ray diffraction confirmed that OCP can remain stable even in the presence of water glass. In a rabbit calvarial defect model, W-OCP increased the bone area by 22.4 %, which was significantly higher than that of defects only at week 4 (p < 0.05). In clinical trials, the new bone formation rate was 49.5 %, confirming that W-OCP had an extremely high application potential as a new bone graft material. After treating MG-63 cells with a W-OCP elution medium, changes in gene expression levels that promoted bone formation were verified via microarray analysis. From the results, W-OCP can be inferred that sodium and silicate ions in water glass play an important role in the recruitment of osteoblasts, significantly increasing the bone growth rate at the early implantation stages. The obtained results suggest that W-OCP can be potentially applied as a new type of synthetic bone materials.

Glass ionomer cement (GIC) is composed of anionic polyacrylic acid and a silica-based inorganic powder. GIC is used as a filling material in the decayed cavity of the tooth; therefore, compatibility with the tooth tissue is essential. In the present study, we aimed to improve the histocompatibility of GIC by introducing nano-hydroxyapatite (nHA), a component of teeth, into a silica-based inorganic powder. CFAS-nHA was prepared by chemically bonding nanorod hydroxyapatite (nHA) to the surface of calciumfluoroaluminosilicate (CFAS). The synthesis of CFAS-nHA was confirmed using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The prepared CFAS-nHA was mixed with polyacrylic acid and cured to prepare GIC containing nHA (GIC-nHA). Cytocompatibility tests of GIC-nHA and GIC were performed using osteoblasts. Osteoblast activity and bone formation ability were superior after GIC-nHA treatment than after control GIC treatment. This enhanced histocompatibility is believed to be due to the improvement of the biological activity of osteoblasts induced by the HA introduced into the GIC. Therefore, to enhance its compatibility with dental tissues, GIC could be manufactured by chemically bonding nHA to the surface of GI inorganic powder.

Biomaterials have been used to supplement and restore function and structure by replacing or restoring parts of damaged tissues and organs. In ancient times, the medical use of biomaterials was limited owing to infection during surgery and poor surgical techniques. However, in modern times, the medical applications of biomaterials are diversifying owing to great developments in material science and medical technology. In this paper, we introduce biomaterials, focusing on calcium phosphate ceramics, including octacalcium phosphate, which has recently attracted attention as a bone graft material.

3D printing technology using calcium phosphate materials such as octacalcium phosphate (OCP, Ca 8 H 2 [PO 4 ] 6 ·5H 2 O) has emerged as a precise approach for fabricating personalized patient-specific constructs. However, the properties of materials and binder solutions for 3D printing may affect the optimal level of biocompatibility. Therefore, in this study, the OCP material was combined with a sodium alginate solution in a 3D printing paste to improve its biocompatibility. Moreover, Alg-OCP and 3D printing scaffolds increased the ALP activity and induced osteogenic differentiation without cytotoxicity in MG-63 cells. This study indicates the potential of Alg-OCP and 3D printing scaffold for novel bone graft materials. Graphical abstract

As a new wet chemical method, polymer template strategy uses monomer polymerization to form a continuous carbon network. The carbon skeleton can make the carbothermal reduction reaction take place in the original, thus preventing the excessive agglomeration of grains. The Al2O3 / C ceramic precursor were obtained by polymer template strategy, and then AlON powders with 3 mu m size were synthesized through a spark plasma sintering (SPS) method at 1,650 degrees C. We confirmed that a continuous network of carbon chains was formed by polymerization to encapsulate the alumina powder, so as to reduce the contact growth of the grains during the high-temperature carbothermal reaction. We established that, when the mass ratio of carbon source to alumina was 1.6:10, the pure AlON powder could be prepared by calcining at 1,650 degrees C for 20 min in a flowing nitrogen atmosphere.

Bioceramics are calcium-phosphate-based materials used in medical and dental implants for replacing or repairing damaged bone tissues; however, the effect of bioceramic sintering on the intracellular signaling pathways remains unknown. In order to address this, we analyzed the impact of sintering on the cell signaling pathways of osteoblast cells using sintered and non-sintered hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP). X-ray diffraction indicated that only the morphology of HA was affected by sintering; however, the sintered bioceramics were found to have elevated the calcium concentrations in relation to the non-sintered variants. Both bioceramics inhibited the JNK signaling pathway; the sintered HA exhibited half the value of the non-sintered variant, while the sintered β-TCP rarely expressed a p-JNK value. The total Src and Raptor protein concentrations were unaffected by the sintering, while the p-Src concentrations were decreased. The p-EGFR signaling pathway was regulated by the non-sintered bioceramics, while the p-p38 concentrations were reduced by both the sintered β-TCP and HA. All of the bioceramics attenuated the total AKT concentrations, particularly the non-sintered HA, and the AKT phosphorylation concentration, except for the non-sintered β-TCP. Thus, the sintering of bioceramics affects several intracellular signaling pathways. These findings may elucidate the bioceramic function and expand their application scope as novel substrates in clinical applications.

Octacalcium phosphate (OCP), a type of bioactive ceramics, may be associated with dentine, tooth apatite, and especially bone generation, and promotes wound healing after fracture. Recently, commercial bone grafting products containing a large amount of OCP material have been released because OCP can be synthesized in large quantities. It is reported to increase cell proliferation, but the interaction between OCP and cell signaling pathways is still unclear. In this study, first, we demonstrated OCP mediated cell signaling pathways with only purified OCP materials. OCP regulated P38, JNK (c-Jun N-terminal kinase), Src, and AKT (protein kinase B) signaling pathways. OCP crystals appeared in the characteristic ribbon shape but varied by several tens of micrometers in size. The X-ray diffraction pattern was the same as previously reported. We studied two concentrations of OCP (10 mg/ml and 20 mg/ml) to understand whether the effect of OCP on cell signaling pathways is dose dependent. We confirmed that OCP treatment affected cell proliferation and alkaline phosphatase and disrupted Src phosphorylation but did not change the total protein level. P38 phosphorylation was activated with OCP treatment and inhibited by SB203580, but P38 total protein level did not change. OCP inhibited JNK phosphorylation signaling, whereas PD98509 inhibited JNK phosphorylation with or without OCP. Interestingly, the AKT total level decreased after OCP treatment, but AKT phosphorylation increased considerably. Our results demonstrate that OCP materials modulate cell signaling pathways and increase cell proliferation.

The electric flash generated by an electric field aided the sintering of hydroxyapatite (HA) in relatively less time and at lower furnace temperatures than the conventional sintering method. The current work has reported a comparative study to explain thermodynamically the effects of the increasing DC electric field strength at 1000°C and 1100°C sintering furnace temperatures during flash sintering in terms of the grain growth and densification of the HA in air. The abrupt change in current density and conductivity of HA during the flash peak correlates the high grain growth and rapid densification with increasing electric field strength. The increased electric field strength reduced the power dissipation from the HA. The abrupt high-rise grain growth phenomenon during flash sintering might consist of the thermal effect and enhancement in ionic conductivity due to the application of an electric field.

This prospective single-arm clinical study aimed to radiographically and histomorphometrically evaluate the efficacy of the lateral approach for sinus floor elevation (LSFE) using biomimetic octacalcium phosphate (OCP) synthetic bone graft (Bontree®). LSFE using Bontree® was performed on 10 patients (15 implant placement sites) willing to undergo implant surgery, followed by implant placements after 6 months of the healing period. The vertical bone height (VBH) and Hounsfield unit (HU) values at each implant placement site were evaluated radiographically using cone-beam computed tomography at baseline immediately after surgery (T1) and 6 months after surgery (T2). A histomorphometric evaluation of the bone core biopsy specimen was also performed. The mean VBH and HU changes at all sites included a decrease by 0.91 mm and a statistically significant increase by 431.86, respectively, from T1 to T2. The mean ratio of the newly formed bone (23.34% ± 10.63%) was greater than that of the residual bone graft (19.09% ± 8.74%), indicating that Bontree® is effective for new bone formation. This pilot study suggests that Bontree® is a promising bone substitute for LSFE.

Octacalcium phosphate (OCP) is a precursor of biological apatite crystals that has attracted attention as a possible bone substitute. On the other hand, few studies have examined this material at the experimental level due to the limitations on OCP mass production. Recently, mass production technology of OCP was developed, and the launch of OCP bone substitutes is occurring. In this study, the bone regeneration capacity of OCP products was compared with two of the most clinically used materials: heat-treated bovine bone (BHA) and sintered biphasic calcium phosphate (BCP). Twelve rabbits were used, and defects in each tibia were filled with OCP, BHA, BCP, and left unfilled as control (CON). The tibias were harvested at 4 and 12 weeks, and 15 μm slides were prepared using the diamond grinding method after being embedded in resin. Histological and histomorphometric analyses were performed to evaluate the bone regeneration ability and mechanism. The OCP showed significantly higher resorption and new bone formation in both periods analysed (p < 0.05). Overall, OCP bone substitutes can enhance bone regeneration significantly by activating osteoblasts and a rapid phase transition of OCP crystals to biological apatite crystals (mineralization), as well as providing additional space for new bone formation by rapid resorption.

Flash sintering (FS) is becoming a popular densification route for high-temperature oxide ceramics because of its rapid sintering performance. In the current study, bar-shaped hydroxyapatite (HA) specimens were hung between two Pt wire electrodes and consolidated by FS through a direct electric field at a constant furnace temperature (1000°C or 1100°C) in air. The electric field facilitated the sintering of HA at relatively lower furnace temperatures than that obtained using the conventional sintering method. The voltage required for the onset of the flash decreased with increasing furnace temperature. The effects of the DC electric field strength at different sintering furnace temperatures were examined in terms of the phase evolution and stability of HA. HA phase dissociation was not observed regardless of the electric field strength or furnace temperature because of the very short FS time. Higher grain growth with fast densification in the flashed-sintered HA samples occurred with increasing electric field strength at each furnace temperature.

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®) in vitro, in vivo, and in clinical cases. Material characterization of Bontree® 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® granules were uniformly composed mainly of OCP. The receptor activator of NF-κB ligand (RANKL) and alkaline phosphatase (ALP) activities of MG63 cells were assessed and used to compare Bontree® with a commercial biphasic calcium phosphate ceramic (MBCP+TM). Compared with MBCP+TM, Bontree® suppressed RANKL and increased ALP activity. A rabbit tibia model used to examine the effects of granule size of Bontree® grafts showed that 1.0 mm Bontree® granules had a higher new bone formation ability than 0.5 mm Bontree® granules. Three clinical cases using Bontree® 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® for bone regeneration.

Modern technology, including 3D printing, provides enormous potential for shape- and size-tailored treatments, especially in orthopedic surgery and dentistry. However, for a medical device produced in the clinical setting that is not compatible with autoclaving or gas sterilization, the choices are very limited, especially because there are a lot of obstacles to using a radiation facility to sterilize a few small-size devices. The goal of this study was to verify the efficacy of laser sterilization of discs made from hydroxyapatite (HA), a material that can be 3D printed and widely used as bone substitute. For this purpose, we compared sterilization efficacy for E. coli and S. mutans when using a range of laser, γ-ray, and e-beam irradiation. Furthermore, we compared biocompatibility by culturing adult stem cells and MC3T3-E1 on HA discs before and after irradiation. Irradiation by UV-C (266 nm) at 100 mJ/cm2 showed 3 kGy of γ-ray or e-beam equivalent sterilization efficacy, without causing physical or chemical changes in the HA discs. In conclusion, in addition to offering affordable maintenance costs, laser sterilization can be used in small-size facilities and can sterilize an object within nanoseconds; this demonstrates its potential to be used on custom small-size medical devices as an alternative sterilization technique that can replace autoclaving, gas sterilization, or the use of radiation facilities.

Low toughness and wear resistance have limited application of many bioceramics in biomedical applications requiring load bearing capability. Spark plasma sintering (SPS) has widened the envelope of processing conditions available to produce bioceramics with new microstructural architectures. SPS has enabled realisation of transparent hydroxyapatite (HA) by providing the means to consolidate fully dense nanostructured HA. Recently, low-dimensional carbon nanomaterials, including carbon nanotubes (CNTs) and graphene/graphene nanoplatelets (GNP) have gained increasing attention as reinforcements due to their providing superior mechanical properties, favourable biocompatibility, and large specific surface area. Processing of these nanocomposites is done using SPS in order to consolidate the ceramics to full density in short time periods, while retaining the structure and properties of the nanomaterial reinforcements. This review focuses on recent progress on GNP/CNT reinforced HA and alumina nanocomposites, including mechanical properties, tribological behaviour, processing conditions, and mechanisms. Biocompatibility of these promising bioceramics with various cells/tissues are discussed.

Osteoporosis and other bone defect had become major problem worldwide. The main problem is the imbalance between bone formation and bone resorption process. The disproportion of those process leads to bone impairment such as, increase in rigidity and brittleness. This complication could be tackled by adding identical material to the bone at the deficient area. In this case, octacalcium phosphate (OCP) incorporated with magnesium (Mg) shows favorable indication as bone implant or cement. However, the information of the Mg doped OCP was scarce. In this study Mg doped OCP was synthesized by precipitation method to collect uniform sample. As a result, significant change could be observed in the crystal lattice and the particle size. Besides, the existence of Mg alters the stability of the phase transformation during the synthesis. Those properties transformation thus could be further utilized for the Mg doped OCP to be applied clinically.

The goal of this study is to obtain basic information to improve the bone adhesion of silica components, which are used as the main ingredient in glass ionomer cement (GIC). To achieve this, nanorod hydroxyapatite (nHA) was grafted to the surface of silica cover glass. Surface analysis confirmed nHA was joined to the glass surface and biocompatibility with osteoblasts was investigated. The grafting of nHA on the surface of slide cover glass (Glass) was confirmed by X-ray photoelectron spectroscopy (XPS) and contact angle (θ) measurement. MC3T3-E1 cells were more stretched out on the nHA-grafted cover glass (Glass-nHA) in comparison to the Glass. In addition, the Glass-nHA was more bioactive in supporting the proliferation of MC3T3-E1 cells in comparison to cells seeded on the Glass. The Glass-nHA was to be highly bioactive and this might be useful information for property modification of GIC.

PURPOSE:The purpose of this study was to evaluate the effectiveness of conventional sandblasted, large-grit, acid-etched (SLA) surface coated with a pH buffering solution based on surface wettability, blood protein adhesion, osteoblast affinity, and platelet adhesion and activation.METHODS:Titanium discs and implants with conventional SLA surface (SA), SLA surface in an aqueous calcium chloride solution (CA), and SLA surface with a pH buffering agent (SOI) were prepared. The wetting velocity was measured by the number of threads wetted by blood over an interval of time. Serum albumin adsorption was tested using the bicinchoninic acid assay and by measuring fluorescence intensity. Osteoblast activity assays (osteoblast adhesion, proliferation, differentiation, mineralization, and migration) were also performed, and platelet adhesion and activation assays were conducted.RESULTS:In both the wetting velocity test and the serum albumin adsorption assay, the SOI surface displayed a significantly higher wetting velocity than the SA surface (P=0.000 and P=0.000, respectively). In the osteoblast adhesion, proliferation, differentiation, and mineralization tests, the mean values for SOI were all higher than those for SA and CA. On the osteoblast migration, platelet adhesion, and activation tests, SOI also showed significantly higher values than SA (P=0.040, P=0.000, and P=0.000, respectively).CONCLUSIONS:SOI exhibited higher hydrophilicity and affinity for proteins, cells, and platelets than SA. Within the limits of this study, it may be concluded that coating an implant with a pH buffering agent can induce the attachment of platelets, proteins, and cells to the implant surface. Further studies should be conducted to directly compare SOI with other conventional surfaces with regard to its safety and effectiveness in clinical settings.

Porous ceramics are promising materials for a number of functional and structural applications that include thermal insulation, filters, bio-scaffolds for tissue engineering, and preforms for composite fabrication. These applications take advantage of the special characteristics of porous ceramics, such as low thermal mass, low thermal conductivity, high surface area, controlled permeability, and low density. In this review, we emphasize the direct foaming method, a simple and versatile approach that allows the fabrication of porous ceramics with tailored microstructure, along with distinctive properties. The wet foam stability is achieved under the controlled addition of amphiphiles to the colloidal suspension, which induce in situ hydrophobization, allowing the wet foam to resist coarsening and Ostwald ripening upon drying and sintering. Different components, like contact angle, adsorption free energy, air content, bubble size, and Laplace pressure, play vital roles in the stabilization of the particle stabilized wet foam to the porous ceramics. The mechanical behavior of the load-displacements curves of sintered samples was investigated using Herzian indentations testes. From the collected results, we found that microporous structures with pore sizes from 30 mu m to 570 mu m and the porosity within the range from 70% to 85%.