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Osamu Suzuki - One of the best experts on this subject based on the ideXlab platform.
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Octacalcium Phosphate bone substitute materials comparison between properties of biomaterials and other calcium Phosphate materials
Dental Materials Journal, 2020Co-Authors: Osamu Suzuki, Yukari Shiwaku, Ryo HamaiAbstract:Octacalcium Phosphate (OCP) is a material that can be converted to hydroxyapatite (HA) under physiological environments and is considered a mineral precursor to bone apatite crystals. The structure of OCP consists of apatite layers stacked alternately with hydrated layers, and closely resembles the structure of HA. The performance of OCP as a bone substitute differs from that of HA materials in terms of their osteoconductivity and biodegradability. OCP manifests a cellular phagocytic response through osteoclast-like cells similar to that exhibited by the biodegradable material β-tricalcium Phosphate (β-TCP). The use of OCP for human cranial bone defects involves using its granule or composite form with one of the natural polymers, viz., the reconstituted collagen. This review article discusses the differences and similarities in these calcium Phosphate (Ca-P)-based materials from the viewpoint of the structure and their material chemistry, and attempts to elucidate why Ca-P materials, particularly OCP, display unique osteoconductive property.
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Chemical Stability-Sensitive Osteoconductive Performance of Octacalcium Phosphate Bone Substitute in an Ovariectomized Rat Tibia Defect
ACS Applied Bio Materials, 2020Co-Authors: Kazuyoshi Baba, Yukari Shiwaku, Takahisa Anada, Kaori Tsuchiya, Ryo Hamai, Yu Mori, Itsuki Oizumi, Naohisa Miyatake, Eiji Itoi, Osamu SuzukiAbstract:The purpose of this study was to investigate whether the chemical condition of osteoporotic serum affects the chemical stability of Octacalcium Phosphate (OCP) and its osteoconductive property. The...
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angiogenesis involvement by Octacalcium Phosphate gelatin composite driven bone regeneration in rat calvaria critical sized defect
Acta Biomaterialia, 2019Co-Authors: Tsuyoshi Kurobane, Yukari Shiwaku, Takahisa Anada, Kaori Tsuchiya, Tetsu Takahashi, Kazuyoshi Baba, Ryo Hamai, Masahiro Iikubo, Osamu SuzukiAbstract:Abstract Effect of Octacalcium Phosphate/gelatin composite (OCP/Gel) on angiogenesis was studied by its implantation in rat calvaria critical-sized defect in relation to bone regeneration for 2 and 4 weeks. The implantation of OCP/Gel disks was analyzed by radiomorphometry using a radiopaque material perfusion (Microfil®) method and histomorphometry by hematoxylin and eosin-staining before and after the decalcification. Effect of the OCP dose in the range up to 4 mg per well on the capillary-like tube formation by human umbilical vein endothelial cells (HUVECs) was also examined in a transwell cell culture. The results showed that the blood vessels formation by OCP/Gel group was significantly higher at 2 weeks than other groups but decreased at 4 weeks during the advancement of new bone formation. The capillary-like tube formation was highest in an OCP dose of 1 mg per well while other OCP doses above or below 1 mg did not show such a stimulatory effect. The results established both in vivo and in vitro confirmed that OCP has a positive effect on angiogenesis during bone regeneration in a suitable dose ranges, suggesting that the angiogenesis stimulated by OCP could be involved in the OCP/Gel-enhanced bone regeneration. Statement of significance We have reported that Octacalcium Phosphate (OCP) materials display stimulatory capacities on the bone tissue-related cells. However, the effect of OCP on the angiogenesis and its relation to the OCP-enhanced bone regeneration is unknown. This study confirmed the capacity of OCP on angiogenesis before increasing the new bone mass after the implantation of a composite of OCP and gelatin (OCP/Gel). The blood vessels formation took place associated with the area beginning of the new bone formation, which finally decreased together with development of bone formation. Because OCP was ascertained stimulating the capillary-like tube formation in HUVEC culture with a certain OCP dose, the present study is the first report showing the capacity of OCP on angiogenesis during the OCP/Gel-enhanced bone regeneration.
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Capacity of Octacalcium Phosphate to promote osteoblastic differentiation toward osteocytes in vitro
Acta Biomaterialia, 2018Co-Authors: Yukari Shiwaku, Takahisa Anada, Kaori Tsuchiya, Tetsu Takahashi, Osamu SuzukiAbstract:Abstract Octacalcium Phosphate (OCP) has been shown to act as a nucleus for initial bone deposition and enhancing the early stages of osteoblastic differentiation. However, the effect on differentiation at the late stage into osteocytes has not been elucidated. The present study was designed to investigate whether OCP can promote the differentiation lineage from osteoblasts to late osteocytes using a clonal cell line IDG-SW3 compared to commercially available sintered β-tricalcium Phosphate (β-TCP) and hydroxyapatite (HA) in a transwell cell culture. Special attention was paid to detect the progress of OCP hydrolysis associated with ionic dissolution products from this material. OCP induced the appearance of an alkaline phosphatase (ALP) peak in the IDG-SW3 cells compared to β-TCP and HA and increased SOST/sclerostin and FGF23 gene expression after 35 days of incubation. Analyses by X-ray diffraction, curve fitting of Fourier transform infrared spectra, and acid Phosphate inclusion of the materials showed that OCP tended to hydrolyze to an apatitic structure during the incubation. Since the hydrolysis enhanced inorganic Phosphate ion (Pi) release from OCP in the media, IDG-SW3 cells were further incubated in the conditioned media with an increased concentration of Pi in the presence or absence of phosphonoformic acid (PFA), which is an inhibitor of Pi transport within the cells. An increase in Pi concentration up to 1.5 mM raised ALP activity, while its positive effect was eliminated in the presence of 0.1 to 0.5 mM PFA. Calcium ions did not show such an effect. These results indicate the stimulatory capacity of OCP on osteoblastic differentiation toward osteocytes. Statement of Significance Octacalcium Phosphate (OCP) has been shown to have a superior osteoconductivity due to its capacity to enhance initial stage of osteoblast differentiation. However, the effect of OCP on the late osteoblastic differentiation into osteocyte is unknown. This study showed the capacity associated with the structural change of OCP. The data show that OCP released inorganic Phosphate (Pi) ions while the hydrolysis advanced if soaked in the media, determined by chemical and physical analyses, and enhanced osteocytes differentiation of IDG-SW3 cells more than hydroxyapatite (HA) and β-tricalcium Phosphate (β-TCP). Conditioned elevated Pi-containing media in the absence of OCP enhanced the osteocyte differentiation in the range of the concentration induced by OCP, the effect of which was cancelled by the inhibitor of Pi-transporters.
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Octacalcium Phosphate collagen composite facilitates bone regeneration of large mandibular bone defect in humans
Journal of Tissue Engineering and Regenerative Medicine, 2017Co-Authors: Tadashi Kawai, Keiko Matsui, Yuji Tanuma, Tetsu Takahashi, Osamu Suzuki, Shinji KamakuraAbstract:Recently it was reported that the implantation of Octacalcium Phosphate (OCP) and collagen composite (OCP-collagen) was effective at promoting bone healing in small bone defects after cystectomy in humans. In addition, OCP-collagen promoted bone regeneration in a critical-sized bone defect of a rodent or canine model. In this study, OCP-collagen was implanted into a human mandibular bone defect with a longer axis of approximately 40 mm, which was diagnosed as a residual cyst with apical periodontitis. The amount of OCP-collagen implanted was about five times greater than the amounts implanted in previous clinical cases. Postoperative wound healing was satisfactory and no infection or allergic reactions occurred. The OCP-collagen-treated lesion was gradually filled with radio-opaque figures, and the alveolar region occupied the whole of the bone defect 12 months after implantation. This study suggests that OCP-collagen could be a useful bone substitute material for repairing large bone defects in humans that might not heal spontaneously. Copyright © 2015 John Wiley & Sons, Ltd.
Shinji Kamakura - One of the best experts on this subject based on the ideXlab platform.
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clinical study of Octacalcium Phosphate and collagen composite in oral and maxillofacial surgery
Journal of Tissue Engineering, 2020Co-Authors: Tadashi Kawai, Keiko Matsui, Shinji Kamakura, Masayuki Fukuda, Hiroshi Takano, Mitsuyoshi Iino, Shigeo Ishikawa, Hiromasa Kawana, Tomoya SomaAbstract:Octacalcium Phosphate and its collagen composite have been recognized as bone substitute materials possessing osteoconductivity and biodegradation properties. We evaluated the effectiveness of Octacalcium Phosphate and its collagen composite used for bone augmentation in major oral and maxillofacial surgeries in a clinical trial. Octacalcium Phosphate and its collagen composite were used in cases of sinus floor elevation in 1- and 2-stage, socket preservation, cyst, and alveolar cleft procedures. A total of 60 patients were evaluated for effectiveness after the implantation of Octacalcium Phosphate and its collagen composite. Although sinus floor elevation in 1-stage, cyst, and alveolar cleft cases met the criteria for the judgment of success, sinus floor elevation in 2-stage and socket preservation groups did not meet the criteria in the initial evaluation. However, an additional evaluation for reconfirmation revealed the effectiveness of Octacalcium Phosphate and its collagen composite in those groups, and all evaluation results ultimately indicated the success of this clinical trial. Therefore, this clinical trial suggested that application of Octacalcium Phosphate and its collagen composite for oral and maxillofacial surgery was safe and effective and that Octacalcium Phosphate and its collagen composite could be a bone substitute candidate instead of autologous bone.
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Octacalcium Phosphate collagen composite facilitates bone regeneration of large mandibular bone defect in humans
Journal of Tissue Engineering and Regenerative Medicine, 2017Co-Authors: Tadashi Kawai, Keiko Matsui, Yuji Tanuma, Tetsu Takahashi, Osamu Suzuki, Shinji KamakuraAbstract:Recently it was reported that the implantation of Octacalcium Phosphate (OCP) and collagen composite (OCP-collagen) was effective at promoting bone healing in small bone defects after cystectomy in humans. In addition, OCP-collagen promoted bone regeneration in a critical-sized bone defect of a rodent or canine model. In this study, OCP-collagen was implanted into a human mandibular bone defect with a longer axis of approximately 40 mm, which was diagnosed as a residual cyst with apical periodontitis. The amount of OCP-collagen implanted was about five times greater than the amounts implanted in previous clinical cases. Postoperative wound healing was satisfactory and no infection or allergic reactions occurred. The OCP-collagen-treated lesion was gradually filled with radio-opaque figures, and the alveolar region occupied the whole of the bone defect 12 months after implantation. This study suggests that OCP-collagen could be a useful bone substitute material for repairing large bone defects in humans that might not heal spontaneously. Copyright © 2015 John Wiley & Sons, Ltd.
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implantation of Octacalcium Phosphate collagen composites ocp col after extraction of canine deciduous teeth achieved undisturbed permanent tooth eruption
Archives of Oral Biology, 2016Co-Authors: Naofumi Kanda, Hiroshi Edamatsu, Keiko Matsui, Yuji Tanuma, Tadashi Kawai, Tetsu Takahashi, Osamu Suzuki, Shinji KamakuraAbstract:Abstract Objective Composite of synthetic Octacalcium Phosphate and collagen (OCP/Col) enhances bone regeneration if implanted into human, canine, or rodent bone defects. This study was designed to investigate the influence on eruption of the permanent successor tooth and alveolar height of OCP/Col implantation into extraction cavities of deciduous teeth. Design Disks of OCP/Col prepared from synthetic granules of Octacalcium Phosphate (OCP) and porcine atelocollagen, and commercially available sintered porous β-tricalcium Phosphate (β-TCP) was implanted into the prepared defect of eleven male beagle dogs by extraction of two deciduous premolars. Untreated group had nothing implanted into the prepared defect, and physiological group (Physiol group) was observed without any treatment. Periodical macroscopic and radiographic examinations were performed until the period equivalent to the physiological eruption of permanent successor teeth (P3 and P4). Results Although no unerupted permanent successor teeth were observed among the OCP/Col, Untreated, and Physiol groups, two permanent successor teeth were unerupted in the β-TCP group. No significant difference of the alveolar heights or the eruptive position in P3 and P4 was observed between OCP/Col and Physiol groups. Conclusion OCP/Col implantation in the alveolar region that included the unerupted permanent successor teeth would cause no disturbance of permanent tooth eruption and preserve the alveolar ridge.
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clinical safety and efficacy of implantation of Octacalcium Phosphate collagen composites in tooth extraction sockets and cyst holes
Journal of Tissue Engineering, 2016Co-Authors: Tadashi Kawai, Keiko Matsui, Yuji Tanuma, Tetsu Takahashi, Osamu Suzuki, Shinji KamakuraAbstract:It was demonstrated that Octacalcium Phosphate collagen composite achieved notable bone regeneration in bone defects in preclinical studies. On the basis of the research results, an investigator-initiated exploratory clinical trial was conducted after approval from a local Institutional Review Board. This clinical study was performed as a single-arm non-randomized intervention study. Octacalcium Phosphate collagen composite was implanted into a total of 10 cases of alveolar bone defects after tooth extractions and cystectomy. Safety assessment was performed in terms of the clinical course and several consecutive laboratory examinations, and sequential radiographs were used for efficacy assessment. All participants uneventfully completed the clinical trial without major problems in their general condition. Postoperative wound swelling was observed, as also commonly seen in tooth extraction or cystectomy. Although no serious liver dysfunction, renal dysfunction, electrolyte imbalance, or abnormal urinalysis results were recognized, the number of white blood cells and C-reactive protein level temporarily increased after the operation. An increase in radiopacity in the Octacalcium Phosphate collagen composite-implanted site was observed in all cases. Finally, the border between the original bone and the Octacalcium Phosphate collagen composite-implanted site became indistinguishable. These results suggest that Octacalcium Phosphate collagen composite could be utilized safely in clinical situations in the future.
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clinical safety and efficacy of implantation of Octacalcium Phosphate collagen composites in tooth extraction sockets and cyst holes
Journal of Tissue Engineering, 2016Co-Authors: Tadashi Kawai, Keiko Matsui, Yuji Tanuma, Tetsu Takahashi, Osamu Suzuki, Shinji KamakuraAbstract:It was demonstrated that Octacalcium Phosphate collagen composite achieved notable bone regeneration in bone defects in preclinical studies. On the basis of the research results, an investigator-in...
Adriana Bigi - One of the best experts on this subject based on the ideXlab platform.
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antiresorptive and anti angiogenetic Octacalcium Phosphate functionalized with bisphosphonates an in vitro tri culture study
Acta Biomaterialia, 2017Co-Authors: Lucia Forte, Elisa Boanini, Paola Torricelli, Massimo Gazzano, Milena Fini, Adriana BigiAbstract:Abstract Development of new materials for the local administration of bisphosphonates (BPs) is aimed to avoid the negative side effects of prolonged systemic use of these potent drugs. In this work, we synthesized Octacalcium Phosphate (OCP) in the presence of two potent BPs and obtained a single crystalline phase up to a zoledronate and alendronate content of 3.5 wt% and 5.2 wt%, respectively. Both BPs provoke minor structural modifications and a reduction of the crystal dimensions of OCP, which suggests a preferential interaction of the BPs with the structure of the calcium Phosphate. Alendronate containing samples display increased values of zeta potential with respect to that of OCP, and an initial burst release of the BP in solution. At variance, the zeta potential of zoledronate functionalized samples decreases on increasing the content of zoledronate, which is not appreciably released in solution. Bone microenvironment response to the composite materials was investigated in vitro using a triculture model. BP functionalized samples downregulate the viability of the cells, sustain osteoblast differentiation and accelerate the production of collagen type I and osteocalcin. At variance, they inhibit monocyte differentiation into osteoclast and provoke a dose dependent reduction of VEGF production, exhibiting antiresorptive and anti-angiogenetic properties that can be usefully exploited for the local treatment of abnormal bone losses. Statement of Significance Bisphosphonates (BPs) are powerful drugs for the treatment of bone diseases. However, BPs systemic administration suffers several undesirable side effects, which stimulate the development of suitable systems for their local administration. In this study we functionalized Octacalcium Phosphate (OCP) with alendronate and zoledronate in order to get biomaterials able to couple the good biological performance of OCP with the therapeutic properties of the BPs. The results provide novel information on the interaction between these two potent BPs and Octacalcium Phosphate. Moreover, the triculture in vitro study indicates that the synthesized composite materials stimulate the production of bone extracellular matrix, inhibit monocytes differentiation into osteoclasts and downregulate the release of Vascular Endothelial Growth Factor (VEGF) in a dose dependent way. The data allow to state that the new composite materials can be usefully employed for the local treatment of diseases involving abnormally high bone resorption.
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antiresorption implant coatings based on calcium alendronate and Octacalcium Phosphate deposited by matrix assisted pulsed laser evaporation
Colloids and Surfaces B: Biointerfaces, 2015Co-Authors: Elisa Boanini, Paola Torricelli, Lucia Forte, S Pagani, Natalia Mihailescu, C Ristoscu, I N Mihailescu, Adriana BigiAbstract:The integration of an implant material with bone tissue depends on the chemistry and physics of the implant surface. In this study we applied matrix assisted pulsed laser evaporation (MAPLE) in order to synthesize calcium alendronate monohydrate (a bisphosphonate obtained by calcium sequestration from Octacalcium Phosphate by alendronate) and calcium alendronate monohydrate/Octacalcium Phosphate composite thin films on titanium substrates. Octacalcium Phosphate coatings were prepared as reference material. The powders, which were synthesized in aqueous medium, were suspended in deionised water, frozen at liquid nitrogen temperature and used as targets for MAPLE experiments. The transfer was conducted with a KrF* excimer laser source (λ = 248 nm, τFWHM ≤ 25 ns) in mild conditions of temperature and pressure. XRD, FTIR and SEM analyses confirmed that the coatings contain the same crystalline phases as the as-prepared powder samples. Osteoblast derived from stem cells and osteoclast derived from monocytes of osteoporotic subjects were co-cultured on the coatings up to 14 days. Osteoclast displayed significantly reduced proliferation and differentiation in the presence of calcium alendronate monohydrate, pointing to a clear role of the coatings containing this bisphosphonate on inhibiting excessive bone resorption. At variance, osteoblast production of alkaline phosphatase and type I pro-collagen were promoted by the presence of bisphosphonate, which also decreased the production of interleukin 6. The positive influence towards osteoblast differentiation was even more enhanced in the composite coatings, thanks to the presence of Octacalcium Phosphate.
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magnesium and strontium doped Octacalcium Phosphate thin films by matrix assisted pulsed laser evaporation
Journal of Inorganic Biochemistry, 2012Co-Authors: Elisa Boanini, Paola Torricelli, I N Mihailescu, Milena Fini, Felix Sima, N Serban, Adriana BigiAbstract:Octacalcium Phosphate (OCP) is a promising alternative to hydroxyapatite as biomaterial for hard tissue repair. In this study we successfully applied Matrix Assisted Pulsed Laser Evaporation (MAPLE) to deposit Mg and Sr doped OCP (MgOCP and SrOCP), as well as OCP, thin films on titanium substrates. OCP, Mg-substituted and Sr-substituted OCP were synthesized in aqueous medium, then were suspended in deionised water, frozen at liquid nitrogen temperature and used as targets for MAPLE experiments. The depositions were carried out using a KrF* excimer laser source (λ = 248 nm, τFWHM = 25 ns) in mild conditions of temperature and pressure. The results of X-ray diffraction, infrared spectroscopy, scanning electron microscopy and energy dispersive spectroscopy investigations revealed that the OCP thin films are deposited in the form of cauliflower-like aggregates and droplets, as well as crystal fragments, with a homogeneous distribution of magnesium and strontium on the surface of the coatings. Human osteoblast-like MG-63 cells were cultured on the different biomaterials up to 14 days. MgOCP and SrOCP coatings promote osteoblast proliferation and differentiation with respect to OCP. Under these experimental conditions, the production of procollagen-type I, transforming growth factor-β1, alkaline phosphatase and osteocalcin indicated that the level of differentiation of the cells grown on the different coatings increased in the order OCP < MgOCP < SrOCP.
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collapsed Octacalcium Phosphate stabilized by ionic substitutions
Crystal Growth & Design, 2010Co-Authors: Elisa Boanini, Massimo Gazzano, Katia Rubini, Adriana BigiAbstract:We have explored the possibility of introducing biologically relevant ions, namely Sr2+, Mg2+, and Mn2+, into the structure of Octacalcium Phosphate (OCP). OCP with partial substitutions of Sr2+ and Mg2+ for Ca2+ up to 7.4 and 1.0 at%, respectively, was successfully synthesized. On the contrary, Mn2+ completely inhibits OCP crystallization, and it promotes the precipitation of brushite. The incorporation of Sr2+ and Mg2+ disturbs the shape of the crystals and reduces the stability of OCP structure. The analysis of the structural modifications occurring during heat treatment puts into evidence that the transformation of OCP into apatite involves a crystalline phase, “collapsed OCP”, resulting from loss of structural water molecules. The main characteristic features of this phase are the small angle reflection at about and 17.0 A (2θ = 5.2°) and the reflection at 8.6 A (2θ = 10.3°). Due to the destabilizing effect of the foreign ions, in the temperature range of 170−250 °C, Mg- and Sr-OCP contain “collapsed...
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biocompatible nanocrystalline Octacalcium Phosphate thin films obtained by pulsed laser deposition
Biomaterials, 2004Co-Authors: G Socol, Paola Torricelli, Adriana Bigi, Barbara Bracci, Monica Iliescu, F Miroiu, J Werckmann, I N MihailescuAbstract:We extended for the first time pulsed laser ablation to the deposition of Octacalcium Phosphate Ca8H2(PO4)6.5H2O (OCP) thin films. The depositions were performed with a pulsed UV laser source (lambda=248 nm, tau> or =20 ns) in a flux of hot water vapors. The targets were sintered from crystalline OCP powder and the laser ablation fluence was set at values of 1.5-2 J/cm2. During depositions the collectors, Si or Ti substrates, were maintained at a constant temperature within the range 20-200 degrees C. The resulting structures were submitted to heat treatment in hot water vapors for up to 6 h. The best results were obtained at a substrate temperature of 150 degrees C during both deposition and post-deposition treatment. High-resolution electron microscopy and XRD at grazing incidence indicated that the coatings obtained were made of nanocrystalline OCP. Cross-section TEM investigations showed that the coatings contained droplets stacked on Ti substrates as well as distributed across the entire thickness of the arborescence-like structure layers. The results of WST-1 assay, cell adherence, DNA replication, and caspase-1 activity confirmed the good biocompatibility of the coatings.
Takahisa Anada - One of the best experts on this subject based on the ideXlab platform.
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Chemical Stability-Sensitive Osteoconductive Performance of Octacalcium Phosphate Bone Substitute in an Ovariectomized Rat Tibia Defect
ACS Applied Bio Materials, 2020Co-Authors: Kazuyoshi Baba, Yukari Shiwaku, Takahisa Anada, Kaori Tsuchiya, Ryo Hamai, Yu Mori, Itsuki Oizumi, Naohisa Miyatake, Eiji Itoi, Osamu SuzukiAbstract:The purpose of this study was to investigate whether the chemical condition of osteoporotic serum affects the chemical stability of Octacalcium Phosphate (OCP) and its osteoconductive property. The...
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angiogenesis involvement by Octacalcium Phosphate gelatin composite driven bone regeneration in rat calvaria critical sized defect
Acta Biomaterialia, 2019Co-Authors: Tsuyoshi Kurobane, Yukari Shiwaku, Takahisa Anada, Kaori Tsuchiya, Tetsu Takahashi, Kazuyoshi Baba, Ryo Hamai, Masahiro Iikubo, Osamu SuzukiAbstract:Abstract Effect of Octacalcium Phosphate/gelatin composite (OCP/Gel) on angiogenesis was studied by its implantation in rat calvaria critical-sized defect in relation to bone regeneration for 2 and 4 weeks. The implantation of OCP/Gel disks was analyzed by radiomorphometry using a radiopaque material perfusion (Microfil®) method and histomorphometry by hematoxylin and eosin-staining before and after the decalcification. Effect of the OCP dose in the range up to 4 mg per well on the capillary-like tube formation by human umbilical vein endothelial cells (HUVECs) was also examined in a transwell cell culture. The results showed that the blood vessels formation by OCP/Gel group was significantly higher at 2 weeks than other groups but decreased at 4 weeks during the advancement of new bone formation. The capillary-like tube formation was highest in an OCP dose of 1 mg per well while other OCP doses above or below 1 mg did not show such a stimulatory effect. The results established both in vivo and in vitro confirmed that OCP has a positive effect on angiogenesis during bone regeneration in a suitable dose ranges, suggesting that the angiogenesis stimulated by OCP could be involved in the OCP/Gel-enhanced bone regeneration. Statement of significance We have reported that Octacalcium Phosphate (OCP) materials display stimulatory capacities on the bone tissue-related cells. However, the effect of OCP on the angiogenesis and its relation to the OCP-enhanced bone regeneration is unknown. This study confirmed the capacity of OCP on angiogenesis before increasing the new bone mass after the implantation of a composite of OCP and gelatin (OCP/Gel). The blood vessels formation took place associated with the area beginning of the new bone formation, which finally decreased together with development of bone formation. Because OCP was ascertained stimulating the capillary-like tube formation in HUVEC culture with a certain OCP dose, the present study is the first report showing the capacity of OCP on angiogenesis during the OCP/Gel-enhanced bone regeneration.
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Capacity of Octacalcium Phosphate to promote osteoblastic differentiation toward osteocytes in vitro
Acta Biomaterialia, 2018Co-Authors: Yukari Shiwaku, Takahisa Anada, Kaori Tsuchiya, Tetsu Takahashi, Osamu SuzukiAbstract:Abstract Octacalcium Phosphate (OCP) has been shown to act as a nucleus for initial bone deposition and enhancing the early stages of osteoblastic differentiation. However, the effect on differentiation at the late stage into osteocytes has not been elucidated. The present study was designed to investigate whether OCP can promote the differentiation lineage from osteoblasts to late osteocytes using a clonal cell line IDG-SW3 compared to commercially available sintered β-tricalcium Phosphate (β-TCP) and hydroxyapatite (HA) in a transwell cell culture. Special attention was paid to detect the progress of OCP hydrolysis associated with ionic dissolution products from this material. OCP induced the appearance of an alkaline phosphatase (ALP) peak in the IDG-SW3 cells compared to β-TCP and HA and increased SOST/sclerostin and FGF23 gene expression after 35 days of incubation. Analyses by X-ray diffraction, curve fitting of Fourier transform infrared spectra, and acid Phosphate inclusion of the materials showed that OCP tended to hydrolyze to an apatitic structure during the incubation. Since the hydrolysis enhanced inorganic Phosphate ion (Pi) release from OCP in the media, IDG-SW3 cells were further incubated in the conditioned media with an increased concentration of Pi in the presence or absence of phosphonoformic acid (PFA), which is an inhibitor of Pi transport within the cells. An increase in Pi concentration up to 1.5 mM raised ALP activity, while its positive effect was eliminated in the presence of 0.1 to 0.5 mM PFA. Calcium ions did not show such an effect. These results indicate the stimulatory capacity of OCP on osteoblastic differentiation toward osteocytes. Statement of Significance Octacalcium Phosphate (OCP) has been shown to have a superior osteoconductivity due to its capacity to enhance initial stage of osteoblast differentiation. However, the effect of OCP on the late osteoblastic differentiation into osteocyte is unknown. This study showed the capacity associated with the structural change of OCP. The data show that OCP released inorganic Phosphate (Pi) ions while the hydrolysis advanced if soaked in the media, determined by chemical and physical analyses, and enhanced osteocytes differentiation of IDG-SW3 cells more than hydroxyapatite (HA) and β-tricalcium Phosphate (β-TCP). Conditioned elevated Pi-containing media in the absence of OCP enhanced the osteocyte differentiation in the range of the concentration induced by OCP, the effect of which was cancelled by the inhibitor of Pi-transporters.
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comparative study on the resorbability and dissolution behavior of Octacalcium Phosphate β tricalcium Phosphate and hydroxyapatite under physiological conditions
Dental Materials Journal, 2016Co-Authors: Susumu Sakai, Takahisa Anada, Kaori Tsuchiya, Hajime Yamazaki, H C Margolis, Osamu SuzukiAbstract:The dissolution behaviors of Octacalcium Phosphate (OCP), β-tricalcium Phosphate (β-TCP), and hydroxyapatite (HA) were compared by implanting the materials in rat subcutaneous pouches for 8 weeks using a filter chamber or immersing them in simulated body fluid (SBF) or Tris-HCl buffer for 2 weeks at pH 7.4 and 37(o)C. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and chemical analysis were conducted on these materials. Degree of supersaturation (DS) in the two solutions immersed with each calcium Phosphate material was calculated from their chemical compositions. The results showed that OCP partially converted to apatitic crystals, while β-TCP and HA remained unchanged after the implantation. The DS of the SBF solution remained slightly supersaturated with respect to OCP and β-TCP, but slightly undersaturated in the Tris-HCl buffer. These findings suggest that previously reported OCP and β-TCP biodegradation could be induced through cell-mediated osteoclastic resorption rather than a simple dissolution process.
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synthetic Octacalcium Phosphate enhanced reparative dentine formation via induction of odontoblast differentiation
Journal of Tissue Engineering and Regenerative Medicine, 2015Co-Authors: Xiaogu Wang, Takahisa Anada, Osamu Suzuki, Tetsuo Suzawa, Tomohiko Miyauchi, Baohong Zhao, Rika Yasuhara, Masanori Nakamura, Ryutaro KamijoAbstract:Synthetic Octacalcium Phosphate (OCP) has been suggested to be a useful biomaterial for the regeneration of hard tissues, including bone. However, it remains unknown whether OCP induces dentine formation by dental pulp. We investigated biomineralization of dental pulp exposed to synthetic OCP in vitro and in vivo. When dental pulp was exposed directly to OCP, rapid formation of reparative dentine (RD) was induced and expression of dentine sialoprotein synthesis was observed in dental pulp adjacent to newly synthesized RD. OCP inhibited the proliferation of rat pulp cells and also promoted their odontoblastic differentiation in vitro, as alkaline phosphatase activity, mineralization of pulp cells and the expression level of dentine sialophosphoprotein were enhanced. Direct contact between OCP and pulp cells is required for OCP to exhibit its effects in vitro. The expression level of Runx2, a transcription factor whose downregulation is closely related to odontoblast differentiation, was downregulated in pulp cells cultured with OCP. Structural changes of OCP during culture were determined by Fourier transform infrared spectroscopy. OCP tended to be converted to carbonate hydroxyapatite after incubation with or without pulp cells, which may be analogous to biological apatite crystals. Taken together, our data suggest that synthetic OCP supports RD formation by dental pulp and downregulation of Runx2 may be involved in that stimulatory activity. Furthermore, OCP–apatite conversion is involved in this stimulatory capacity of OCP. Copyright © 2013 John Wiley & Sons, Ltd.
Yoshitomo Honda - One of the best experts on this subject based on the ideXlab platform.
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Effect of addition of hyaluronic acids on the osteoconductivity and biodegradability of synthetic Octacalcium Phosphate.
Acta biomaterialia, 2013Co-Authors: Kentaro Suzuki, Takahisa Anada, Yoshitomo Honda, Naohisa Miyatake, Eiji Itoi, Hideki Imaizumi, Koshi N Kishimoto, Tatsuya Miyazaki, Masami Hosaka, Osamu SuzukiAbstract:The present study was designed to investigate whether three sodium hyaluronic acid (HyA) medical products, Artz(®), Suvenyl(®) and a chemically modified derivative of sodium HyA Synvisc(®), can be used as suitable vehicles for an osteoconductive Octacalcium Phosphate (OCP). OCP granules (300-500 μm diameter) were mixed with these sodium HyAs with molecular weights of 90 × 10(4) (Artz(®)), 190 × 10(4) (Suvenyl(®)) and 600 × 10(4) (Synvisc(®)) (referred to as HyA90, HyA190 and HyA600, respectively). OCP-HyA composites were injected using a syringe into a polytetrafluoroethylene ring, placed on the subperiosteal region of mouse calvaria for 3 and 6 weeks, and then bone formation was assessed by histomorphometry. The capacity of the HyAs for osteoclast formation from RAW264 cells with RANKL was examined by TRAP staining in vitro. Bone formation was enhanced by the OCP composites with HyA90 and HyA600, compared to OCP alone, through enhanced osteoclastic resorption of OCP. HyA90 and HyA600 facilitated in vitro osteoclast formation. The results suggest that the osteoconductive property of OCP was accelerated by the HyAs-associated osteoclastic resorption of OCP, and therefore that HyA/OCP composites are attractive bone substitutes which are injectable and bioactive materials.
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Granule size-dependent bone regenerative capacity of Octacalcium Phosphate in collagen matrix.
Tissue engineering. Part A, 2012Co-Authors: Yuji Tanuma, Takahisa Anada, Yoshitomo Honda, Tadashi Kawai, Shinji Kamakura, Seishi Echigo, Osamu SuzukiAbstract:The present study was designed to determine whether the osteoconductivity of Octacalcium Phosphate-collagen (OCP/Col) composite can be improved by controlling the granule size of OCP. The granules of synthetic OCP, with diameters in the range of 53 to 300, 300 to 500, and 500 to 1000 μm, were used as an inorganic source of composite materials mixed with atelo-Col. After vacuum dehydrothemal treatment, OCP/Col disks were implanted into critical-sized calvaria defects in Wistar rats for 4, 8, and 12 weeks and examined radiographically, histologically, histomorphometrically, and histochemically. The materials were characterized according to mercury intrusion porosimetry and scanning electron microscopy. X-ray diffraction was performed before and after implantation. The dissolution of OCP crystals in a Col matrix was determined by immersing OCP/Col disks in a culture medium. OCP/Col had a constant pore size (~30 μm) regardless of OCP granule size. OCP in the Col matrix tended to convert to hydroxyapatite (HA) during the implantation. OCP/Col with the smallest granules of OCP enhances both bone regeneration and biodegradation the most through tartrate-resistant acid phosphatase (TRAP)-positive osteoclastic cellular resorption of OCP granules. The smallest OCP granules in the Col matrix showed the highest dissolution and had the greatest potential to form HA. The results indicated that the size of the included OCP granules can controll the osteoconductivity of OCP/Col. The overall results suggest that the physicochemical property of OCP crystals is a factor that determines the bone regenerative capacity of OCP/Col in critical-sized calvaria large bone defects in rats.
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proteome analysis of rat serum proteins adsorbed onto synthetic Octacalcium Phosphate crystals
Analytical Biochemistry, 2011Co-Authors: Hirofumi Kaneko, Takahisa Anada, Yoshitomo Honda, Shinji Kamakura, Junichi Kamiie, Hirotaka Kawakami, Naru Shiraishi, Tetsuya Terasaki, Hidetoshi Shimauchi, Osamu SuzukiAbstract:Abstract The present study was designed to determine which proteins are selectively adsorbed onto two bone substitute materials, Octacalcium Phosphate (OCP) and hydroxyapatite (HA) crystals, from rat serum by proteome analysis. Ground crystals of synthetic OCP and commercially available sintered HA, with the same surface area, were incubated in rat serum proteins at 37 °C for 24 h. The proteins from the crystals extracted with guanidine–HCl–EDTA were listed on the basis of the results of liquid chromatography tandem mass spectrometry (LC/MS/MS). A total of 138 proteins were detected from OCP; 103 proteins were detected from HA. Forty-eight proteins were from both crystals. A quantitative analysis of the proteins detected was performed for the extracted two bone formation-related proteins apolipoprotein E (Apo E), a protein known to promote osteoblast differentiation, and complement 3 (C3). HA adsorbed C3 (3.98 ± 0.03 fmol/μg protein) more than OCP (1.81 ± 0.07 fmol/μg protein) did, while OCP adsorbed Apo E (2.42 ± 0.03 fmol/μg protein) more than HA (1.21 ± 0.01 fmol/μg protein) did even after deleting the high-abundance proteins, such as albumin. The results demonstrated that OCP exhibits a similar property but distinct capacity with HA in adsorbing bone formation-related proteins from the serum constituents.
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mechanical stress related calvaria bone augmentation by onlayed Octacalcium Phosphate collagen implant
Tissue Engineering Part A, 2010Co-Authors: Aritsune Matsui, Takahisa Anada, Yoshitomo Honda, Tadashi Kawai, Shinji Kamakura, Seishi Echigo, Naohisa Miyatake, Taisuke Masuda, Osamu SuzukiAbstract:Previous studies have suggested that the biodegradability of Octacalcium Phosphate–collagen (OCP/Col) composite by osteoclasts is accelerated in association with mechanical stress suffered by the host tissue around the implant. The present study was designed to investigate whether alleviation of mechanical stress restores the bone regenerative properties of OCP/Col, as previously shown in nonload-bearing sites. OCP/Col discs supported with a polytetrafluoroethylene (PTFE) ring, which has a higher modulus than OCP/Col, were implanted in a rat subperiosteal pocket for up to 12 weeks. The structural features of the implant and biological responses were analyzed by X-ray diffraction, Fourier transform infrared spectroscopy, histomorphometry, histochemistry, and tissue mRNA expression around the implants. The effect of compression was analyzed using mouse stromal ST-2 cells by deforming the cell-seeded OCP/Col discs in vitro with or without a PTFE ring. The results clearly indicated the restoration of bone for...
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effect of topography of the Octacalcium Phosphate granule surfaces on its bone regenerative property
2010Co-Authors: Yoshitomo Honda, Takahisa Anada, Shinji Kamakura, Osamu SuzukiAbstract:We have previously reported that synthetic Octacalcium Phosphate (OCP) enhanced differentiation of osteoblasts and osteoclasts in vitro and also the bone regeneration in vivo. While the conversion of OCP into hydroxyapatite (HA) has been considered to be involved in the stimulatory capacity of OCP, little is known about the effect of topography of the OCP granule surface on its osteogenic capability. The present study reviews whether the surface topography of OCP granules, aggregates consisting of randomly oriented plate-like crystals, affects its intrinsic bone regenerative property in vivo. Two OCP granules, showing similar conversion velocity but a different surface topography, induced the distinct bone-forming ability in the calvaria defect of mouse. These results suggest that special attention should be paid for the surface microstructure as well as the conversion velocity in OCP granules to prepare the potent bone regenerative scaffold.