掲載種別：研究論文（学術雑誌）   出版者・発行元：Small Structures  

Hematopoietic stem cell (HSC) transplantation is used to treat blood and immunodeficient diseases. HSC expansion techniques must be developed to prevent complications and ensure reliable therapeutic efficacy. Hence, several studies have attempted in vitro expansion of HSCs using scaffolds but failed to mimic the diverse and complex nature of HSC environments. Herein, an artificial HSC microenvironment, bone marrow (BM) niches is created, through in vivo engineering using carbonate apatite honeycomb scaffolds and the potential of these scaffolds in restoring lost hematopoietic function and immunity is investigated. BM niches are generated in every honeycomb channel, wherein HSCs are gradually aggregated. Compared to the actual BM, the scaffolds exhibit a 9.9- and 78-fold increase in the number of stored CD45− CD34+ side scatterlow cells that are mainly considered HSCs at 8 and 12 weeks, respectively. The transplantation of the honeycomb scaffold containing HSCs and BM niches into immunocompromised mice increases peripheral blood chimerism and restores hematopoietic function and the number of immunocytes (monocytes and lymphocytes) to normal levels. This study contributes to the development of efficient HSC transplantation techniques. Additionally, in vivo-engineered integrated tissues using honeycomb scaffolds can be used to elucidate the interplay between the BM niches and resident cells.

DOI： 10.1002/sstr.202400065

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記述言語：日本語   出版者・発行元：公益社団法人 日本金属学会  

DOI： 10.2320/materia.63.615

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Applied Materials and Interfaces  

Osteoporotic bone defects are difficult to repair in elderly patients. This study aimed to repair osteoporotic bone defects using a combination of bone tissue engineering (BTE) and drug delivery systems (DDS). Herein, honeycomb granules (HCGs) composed of carbonate apatite microspheres were fabricated as BTE scaffolds. Each HCG possesses hexagonal macropores and abundant interconnected micropores between the microspheres. Owing to these multiscale interconnected pores, HCGs can readily contain antibodies against sclerostin (Scl), which causes imbalances in bone homeostasis. Anti-Scl antibody-loaded HCGs (Scl-Ab-HCGs) regulate the release of Scl-Abs in response to the pH of the osteoporotic environment. In ovariectomized rabbit osteoporotic femurs, HCG monotherapy forms new bone with less osteocyte damage (fewer empty bone lacunae) and fewer osteoclasts than osteoporotic bone; however, it is insufficient to prevent receptor activator of nuclear factor-kappa B ligand (RANKL) overexpression. Consequently, HCG monotherapy restores bone quantity better than no treatment but not to normal levels. In contrast, new bone tissue formed by Scl-Ab-HCG-based DDS predominantly expresses osteocalcin rather than RANKL, similar to normal bone, and shows a similar osteocyte apoptosis level, bone quantity, and osteoclast number as normal bone. Thus, Scl-Ab-HCG-based DDS is a promising approach for osteoporotic bone defect repair.

DOI： 10.1021/acsami.4c08047

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Materials Today Bio  

Bone regeneration using synthetic materials has a high rate of surgical site infection, resulting in severe pain for patients and often requiring revision surgery. We propose Ag3PO4-based surface modification and structural control of scaffolds for preventing infections in bone regeneration. We demonstrated the differences in toxicity and antibacterial activity between in vitro and in vivo studies and determined the optimal silver content in terms of overall anti-infection effects, bone regeneration, toxicity, and pigmentation. A honeycomb structure comprising osteoconductive and resorbable carbonate apatite (CAp) was used as the base scaffold. CAp in the scaffold surface was partially replaced with different concentrations of Ag3PO4 via controlled dissolution-precipitation reactions in an AgNO3 solution. Both bone regeneration and infection prevention were achieved at 860–2300 ppm of silver. Despite the absence of Ag3PO4, honeycomb scaffolds were less susceptible to infection, even under conditions where infection occurs in clinically used three-dimensional porous scaffolds. Regardless of in vitro cytotoxicity at >5200 ppm of silver, increasing the silver content to 21,000 ppm did not adversely affect in vivo bone formation and scaffold resorption or cause acute systemic toxicity. Rather, bone formation was enhanced with 5200 ppm of silver. However, pigmentation was observed at that concentration. Hence, we concluded that the optimal silver concentration range is 860–2300 ppm for anti-infective and pigmentation-free bone regeneration. Bone regeneration was achieved via surface modification, resulting in the rapid release of silver ions immediately after implantation, followed by gradual release over several months. The scaffold structure may also aid in preventing bacterial growth within the scaffolds.

DOI： 10.1016/j.mtbio.2024.101161

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人　日本歯科理工学会  

Granular type of bone substitutes is currently used in the field of dentistry to restore alveolar bone defects. However, the migration of the granules from the implantation site is still an unresolved issue. In this study, the feasibility to fabricate self-setting calcium sulfate hemihydrate (CSH) granules using different ranges of loading pressure: CSH(0), CSH(50), CSH(100), and CSH(150) was investigated with the hypothesis that CSH granules with reduced microporosity can inhibit the rapid dissolution rate of the calcium sulfate dihydrate (CSD) set blocks and induce bone regeneration. After 4 weeks of implantation, the granules were mostly replaced with new bone although no significant differences were observed. Nevertheless, the granules demonstrated the ability to set within the bone defect. It is therefore concluded that the setting ability of calcium sulfate can contribute to address the issue of migration of the granules and provide a useful guide for designing setting bone substitutes.

DOI： 10.4012/dmj.2023-248

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出版者・発行元：Ceramics International  

In bone regeneration, synthetic materials are required to replace autogenous bone grafts. The shape, composition, surface, and porous structure of the material are key factors in bone formation and material resorption. In this study, we describe the fabrication of Mg-doped biphasic calcium phosphate (Mg-BCP) granules comprising hydroxyapatite (HAp) and beta-tricalcium phosphate (β-TCP) by exploiting the structural and chemical characteristics of sea urchin spines. The Mg-BCP granules were cylinders with a 1.2–1.8 mm diameter and height of 1.4–1.7 mm. The β-TCP/HAp ratio and Mg content in the Mg-BCP granules were controlled within the ranges of 0.36–0.45 and 2.40–6.21 mol%, respectively. Controlling the β-TCP/HAp ratio and Mg content may contribute to controlling the material resorption rate and promoting osteogenesis and angiogenesis. The Mg-BCP granules maintained the structural characteristics of the sea urchin spines. The granules comprised radial wedges termed septa, and a meshwork termed stereom. The interseptal gaps, or micropores, decreased from the granular exterior (24–29 μm) to the interior (14–28 μm). The septa in the outermost layer provide concavities on the sides of the cylindrical granules. The stereom meshworks in the core and outer layers involved micropores in the ranges of 3–15 and 3–10 μm, respectively. These multiscale pores and surface undulations may improve cell penetration and attachment, bodily fluid permeability, and protein adsorption. The compressive strengths of the Mg-BCP granules were in the range of 45.2–46.1 MPa, which are useful as bone grafts. Due to their rounded shapes, the Mg-BCP granules filled a mold more densely than the clinically used and irregularly shaped granules. These findings demonstrated that Mg-BCP granules are promising materials for bone regeneration.

DOI： 10.1016/j.ceramint.2024.04.341

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記述言語：英語   出版者・発行元：(一社)日本歯科理工学会  

掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of the Australian Ceramic Society  

This study aims to understand the influence of pore size on the compositional, morphological, and functional group characteristics of dicalcium phosphate dihydrate (DCPD)-coated porous β-tricalcium phosphate (β-TCP) granules. This study produced 300–600 μm granular sizes of porous β-TCP granules with various pore diameters. This was achieved by combining dry powders of DCPD and calcium carbonate (CaCO3) [Ca/P ratio: 1.5] with varied quantities of 10%, 20%, 30%, and 40% of sodium chloride (NaCl) powders to obtain mixtures composed of weight percentages (wt%) ratios of 90:10, 80:20, 70:30, and 60:40, respectively. Post-sintering, the porous β-TCP granules fabricated were soaked in an acidic calcium phosphate solution for 30 min to coat the surfaces with DCPD crystals formation via a dissolution-precipitation reaction. Subsequently, the specimens were examined with scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR). The morphological observations demonstrated that increasing NaCl powder up to 40% with a mixture of CaCO3 and DCPD enhanced the β-TCP granules' pore size. Furthermore, The formation of DCPD on and inside the porous β-TCP granules has been accelerated due to the presence of large pores. Conversely, dissolution-precipitation reactions were incomplete on granules with 2.8, 4.9, and 6.91 μm pore sizes. The major XRD peaks of the DCPD and β-TCP phases with 2.8, 4.9, and 6.91 μm pores were also slightly shifted to the right, while granules with 7.53 μm pores demonstrated DCPD and β-TCP peaks aligned with pure β-TCP and DCPD phases. This study's findings are expected to offer insight into the role of pore size in influencing the dissolution-precipitation process that affects the morphological, compositional, and functional group characteristics of DCPD-coated β-TCP granules.

DOI： 10.1007/s41779-024-01029-3

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記述言語：日本語   出版者・発行元：公益社団法人 日本口腔インプラント学会  

<p>骨の無機組成はハイドロキシ（水酸）アパタイトではなく，炭酸アパタイトである．海で生まれた生体は，捕食者からの防御のために海水成分を用いて炭酸カルシウムを組成とする外骨格を形成した．一方，生命体のエネルギー源はリン酸（アデノシン三リン酸など）である．生命体の運動性の向上や，微量のリン酸を含む海中から陸上（空中にはリン酸が存在しない）への移動に伴い，脊椎動物は骨にリン酸を貯蔵した．その結果，脊椎動物の骨格組成は炭酸カルシウムにリン酸を付与した炭酸アパタイトとなった．</p><p>炭酸アパタイト骨補塡材は，上述した生命体の進化に学び炭酸カルシウムにリン酸塩を付与すると調製できる．100％化学合成された炭酸アパタイトは，骨と同じく破骨細胞によって吸収される．細胞間情報伝達によって骨芽細胞が活性化されるため，炭酸アパタイトは圧倒的な骨伝導性を示す．</p><p>多施設治験で有効性が100％であることが証明された．その結果，炭酸アパタイト骨補塡材は日本で初めて適用制限がない骨補塡材として薬事承認され，日米で臨床応用されている．日本ではトップシェアを誇る．</p><p>アパタイトは医用材料として必須である．しかしながらハイドロキシアパタイトは骨の無機組成ではない．治療効果の観点から，ハイドロキシアパタイト関連医用材料を炭酸アパタイトで再構築することが喫緊の課題である．</p>

DOI： 10.11237/jsoi.37.86

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental displacement of granules to unintended locations and leakage of granules from bone defects. Although covering the defect with a barrier membrane prevents granule emanation, this procedure is troublesome. To resolve these problems, we fabricated bioresorbable mesh cages (BRMc) in this study. Bone graft granules composed of carbonate apatite alone (Gr) and bioresorbable mesh cages (BRMc/Gr) introduced the bone graft granules and were implanted into the bone defect in the rabbit femur. Micro-computed tomography and histological analysis were conducted at 4 and 12 weeks after implantation. Osteoprogenitors in the bloodstream from the host bone passed through the pores of BRMc, penetrated the porous structure of graft granules, and might interact with individual granules. Then bone remodeling could progress actively and new bone was formed. The new bone formation was similar to the host bone at 12 weeks and there were minimal signs of local tissue inflammation. BRMc/Gr could reduce the risk of unwanted new bone formation occurring due to loss of granules from the bone defects compared with Gr because BRMc enclosed granules and prevent granules leakage from bone defects and BRMc could not induce unfavorable effects to forme new bone. Additionally, BRMc/Gr could keep granules assembled in one place, avoid displacement of granules to unintended locations, and carry easily. These results demonstrated that BRMc/Gr was effective in bone regeneration and improved clinical handling.

DOI： 10.1038/s41598-024-63067-y

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その他リンク： https://www.nature.com/articles/s41598-024-63067-y

掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology  

Carbonate apatite (CO3Ap)-granules bone substitute exhibits excellent osteoconductivity and replaced by a new bone based on bone remodeling process. However, no improvement has been made so far with respect to the drawbacks of granules; i.e., intraoperative scatter and postoperative migration. The aim of this study was to evaluate the feasibility of fabricating a CO3Ap-granules sponge to overcome these drawbacks. The CO3Ap granules sponge was successfully fabricated by mixing 300–600 µm CO3Ap granules with 3 % atelocollagen, followed by lyophilization at − 70 °C for 24 h and a dehydrothermal treatment at 150 °C for 24 h. The CO3Ap-granules sponge and CO3Ap-granules were implanted into rat calvarial bone defects for 2 and 4 weeks. No significant intraoperative scatter and postoperative migration were evident when the bone defects were reconstructed with the CO3Ap-granules sponge, whereas significant both intraoperative scatter and postoperative migration were observed when the bone defect was reconstructed with CO3Ap granules. Although less osteogenesis was anticipated for the CO3Ap-granules sponge due to the coverage of CO3Ap-granules surface with atelocollagen, no significant differences were observed in bone formation between the CO3Ap-granules sponge and CO3Ap-granules cases because the 3 % atelocollagen and lyophilization kept the CO3Ap granules surface only partially covered. Consequently, the CO3Ap-granules sponge and CO3Ap-granules exhibited similar bone formation at both 2 and 4 weeks after surgery. Thus, the CO3Ap-granules sponge improved the handling performance and retention ability at the bone defects without scarifying the osteogenesis of CO3Ap-granules.

DOI： 10.1016/j.ajoms.2024.05.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Advanced Healthcare Materials  

The aging global population is generating an ever-increasing demand for bone regeneration. Various materials, including blocks, granules, and sponges, are developed for bone regeneration. However, blocks require troublesome shaping and exhibit poor bone-defect conformities; granules migrate into the surrounding tissues during and after filling of the defect, causing handling difficulties and complications; and sponges contain polymers that are subject to religious restrictions, lack osteoconductivity, and may cause inflammation and allergies. Herein, carbonate apatite chains that overcome the limitations of conventional materials are presented. Although carbonate apatite granules migrate, causing inflammation and ectopic calcification, the chains remain in the defects without causing any complications. The chains conform to the defect shape and transform into 3D porous structures, resulting in faster bone regeneration than that observed using granules. Thus, these findings indicate that even traditional calcium phosphates materials can be converted to state-of-the-art materials via shape control.

DOI： 10.1002/adhm.202303245

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記述言語：英語  

DOI： https://doi.org/10.1016/j.ceramint.2024.04.341

出版者・発行元：Journal of the Australian Ceramic Society  

Among the various bone substitutes, carbonate apatite (CO3Ap) has received significant attention in the field of hard tissue regeneration due to its similarity in chemical composition to natural bone and its osteoconductivity and bioresorbability. This study aimed to develop a cost-effective method for fabricating porous CO3Ap blocks while maintaining a balance between porosity and mechanical properties. The level of interconnectivity in the porous structure was achieved by adjusting the pore volume fractions of the starting materials. The phase and microstructure characteristics of the porous CO3Ap blocks were assessed using techniques such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The diametral tensile strength (DTS) of the blocks was determined using a universal testing machine. The results demonstrated that the mechanical strength of the blocks stayed within a range that was suitable for handling properties. This advantage allows the porous blocks to withstand initial stress during implantation procedures or in the early stages of defect healing.

DOI： 10.1007/s41779-023-00954-z

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記述言語：英語  

DOI： https://doi.org/10.3390/biomimetics9020112

記述言語：英語   出版者・発行元：Biomimetics  

Generally, ceramics are brittle, and porosity is inversely correlated with strength, which is one of the challenges of ceramic scaffolds. Here, we demonstrate that lamellar septum-like carbonate apatite scaffolds have the potential to overcome these challenges. They were fabricated by exploiting the cellular structure of the cuttlebone, removing the organic components from the cuttlebone, and performing hydrothermal treatment. Scanning electron microscopy revealed that the scaffolds had a cellular structure with walls between lamellar septa. The interwall and interseptal sizes were 80–180 and 300–500 μm, respectively. The size of the region enclosed by the walls and septa coincided with the macropore size detected by mercury intrusion porosimetry. Although the scaffold porosity was extremely high (93.2%), the scaffold could be handled without disintegration. The compressive stress–strain curve demonstrated that the scaffolds showed layer-by-layer fracture behavior, which seemed beneficial for avoiding catastrophic failure under impact. When the scaffolds were implanted into rabbit femurs, new bone and blood vessels formed within the scaffold cells at 4 weeks. At 12 weeks, the scaffolds were almost entirely replaced with new bone. Thus, the lamellar septum-like cellular-structured carbonate apatite is a promising scaffold for achieving early bone regeneration and compression resistance.

DOI： 10.3390/biomimetics9020112

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記述言語：英語  

DOI： https://doi.org/10.1002/adhm.202303245

記述言語：英語  

DOI： https://www.tandfonline.com/doi/full/10.1080/14686996.2024.2303327

掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Bioprinting  

In the reconstruction of bone defects close to soft tissue, preventing the invasion of fibrous tissue into the bone defect is key to successful bone reconstruction. In this study, we clarified the effects of the pore architecture of artificial bone grafts on the penetration of bone and fibrous tissue, and the orientation of regenerated bone. Carbonate apatite grafts with uniaxial pores along the long- (L-graft) or short-axis (S-graft) direction of the graft and biaxial pores along the long- and short-axes (LS-graft) were used. These grafts were implanted in bone defects created by rabbit ulnae amputation. The pores of the L-, S-, and LS-grafts opened into the bone stumps, muscles, and bone stumps and muscles together, respectively. In the L-graft, the graft pores developed bone from the bone stump to the graft center, while preventing excessive invasion of fibrous tissue. In S- and LS-grafts, the graft pores along the short axis allowed the invasion of fibrous tissue into the grafts. Consequently, although the bone grew to the edge regions in these grafts, further bone ingrowth was inhibited by the fibrous tissue. Furthermore, the pore architecture of the grafts affected the orientation of the regenerated bone. The degree of orientation of the bone formed in the L- and S-grafts was 1.6-fold higher than that formed in the LS-grafts. Thus, controlling the pore architecture allowed the growth of bone to predominate over that of fibrous tissue and induced the formation of bone with an ordered orientation.

DOI： 10.36922/ijb.2323

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出版者・発行元：Ceramics International  

Three-dimensional interconnected porous carbonate apatite (3D-CO3Ap) bone grafts facilitate rapid bone replacement because of their structure, which supports cellular infiltration. Existing 3D-CO3Ap grafts have demonstrated limited mechanical strength, with a maximum compressive strength of 3 MPa. By fusing polymer-bound CaCO3 granules, followed by the debinding and compositional transformation of the granules via a dissolution–precipitation reaction, we successfully fabricated 3D-CO3Ap grafts that exhibited remarkably enhanced compressive strengths, which were recorded at 14.9 ± 3.7 MPa. The use of spherical granules, which provide more uniform and effective intergranular contacts than cylindrical granules, was key to achieving higher mechanical strength and superior bone formation. 3D-CO3Ap developed with spherical granules not only exhibited higher compressive strength, but also enhanced new bone formation compared with those fabricated with cylindrical granules. This study underscores the significance of porous microstructure design in 3D-CO3Ap, highlighting its critical role in optimizing both mechanical properties and bone regeneration capabilities.

DOI： 10.1016/j.ceramint.2024.10.203

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記述言語：日本語   出版者・発行元：一般社団法人 日本人工臓器学会  

DOI： 10.11392/jsao.52.177

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Materials  

The internal structure of the scaffolds is a key factor for bone regeneration. In this study, we focused on the space dimensionality within the scaffold that may control cell migration and evaluated the effects on the size and orientation of blood vessels and the amount of bone formation in the scaffold. The carbonate apatite scaffolds with intrascaffold space allowing one-dimensional (1D), two-dimensional (2D), or three-dimensional (3D) cell migration were fabricated by 3D printing. These scaffolds had the same space size, i.e., distances between the struts (~300 µm). The scaffolds were implanted into the medial condyle of rabbit femurs for four weeks. Both the size and orientation degree of the blood vessels formed in the scaffolds allowing 1D cell migration were 2.5- to 4.0-fold greater than those of the blood vessels formed in the scaffolds allowing 2D and 3D cell migration. Furthermore, the amount of bone formed in the scaffolds allowing 1D cell migration was 1.4-fold larger than that formed in the scaffolds allowing 2D and 3D cell migration. These are probably because the 1D space limited the direction of cell migration and prevented the branching of blood vessels, whereas 2D and 3D spaces provided the opportunity for random cell migration and blood vessel branching. Thus, scaffolds with 1D space are advantageous for inducing large and oriented blood vessels, resulting in a larger amount of bone formation.

DOI： 10.3390/ma16247518

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Colloids and Surfaces B: Biointerfaces  

Osteoconductive ceramics (OCs) are often used to endow polylactic acid (PLA) with osseointegration ability. Conventionally, OC powder is dispersed in PLA. However, considering cell attachment to the implant, OCs may be more favorable when they exist in the form of aggregations, such as granules, and are larger than the cells rather than being dispersed like a powder. In this study, to clarify the effects of the dispersion state of OCs on the osseointegration ability, carbonate apatite (CAp), a bone mineral analog that is osteoconductive and bioresorbable, powder–PLA (P-PLA), and CAp granule–PLA (G-PLA) composite implants were fabricated via thermal pressing. The powder and granule sizes of CAp were approximately 1 and 300–600 µm, respectively. G-PLA exhibited a higher water wettability and released calcium and phosphate ions faster than P-PLA. When cylindrical G-PLA, P-PLA, and PLA were implanted in rabbit tibial bone defects, G-PLA promoted bone maturation compared to P-PLA and pure PLA. Furthermore, G-PLA bonded directly to the host bone, whereas P-PLA bonded across the osteoid layers. Consequently, the bone-to-implant contact of G-PLA was 1.8- and 5.6-fold higher than those of P-PLA and PLA, respectively. Furthermore, the adhesive shear strength of G-PLA was 1.9- and 3.0-fold higher than those of P-PLA and PLA, respectively. Thus, G-PLA achieved earlier and stronger osseointegration than P-PLA or PLA. The findings of this study highlight the significance of the state of dispersion of OCs in implants as a novel strategy for material development.

DOI： 10.1016/j.colsurfb.2023.113588

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Surfaces and Interfaces  

The main reason for revision arthroplasty with an alumina-based prosthesis is aseptic loosening of the prosthesis. To prevent loosening of the prosthesis, endowing bioinert alumina with osteogenic ability is deemed an effective approach. Hence, we developed an alumina substrate with carbonate apatite and evaluated its effectiveness for early binding to the bone. Alumina substrates were coated with carbonate apatite using the following procedures: (1) etching the alumina substrate by alkaline hydrothermal treatment; (2) calcium carbonate coating of the etched alumina substrate; and (3) composition conversion of calcium carbonate coating into carbonate apatite by phosphatization. The tensile bond strength of carbonate apatite coating to alumina substrate was 17.6 MPa, which satisfied the criteria defined by the International Organization for Standardization. Contrary to the results of etched alumina substrates, the carbonate apatite-coated alumina substrates promoted the proliferation and osteogenic differentiation of mesenchymal stem cells and induced mineralization. Furthermore, the carbonate apatite-coated alumina substrates strongly adhered to the rabbit tibia 4 weeks after implantation compared to the etched alumina substrates. The contact area and adhesion strength of carbonate apatite-coated alumina substrates to bone were approximately 19- and 6-fold higher than those of etched alumina substrates, respectively. Thus, carbonate apatite coating may contribute to preventing the loosening of alumina prostheses.

DOI： 10.1016/j.surfin.2022.102617

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Biomedical Materials Research - Part A  

Scaffolds having appropriate mechanical strength and providing a proper microenvironment for osteogenesis are expected to be effective alternatives to autografts for bone regeneration. In this study, ant-nest type porous (ANP) scaffolds consisting of CO3Ap were fabricated using calcium carbonate powder or slurry and two types of polyurethane foam through a dissolution–precipitation reaction. ANP-type, three-dimensional, interconnected porous CO3Ap scaffolds were fabricated by burning out the struts of polyurethane foams embedded in CaCO3, followed by compositional transformation from CaCO3 to CO3Ap. The types of polyurethane foam and impregnation methods of CaCO3 into polyurethane form affected the geometry of the resulting ANP structures. Mechanical and in vivo biological performances of these scaffolds relied on the geometry of the ANP structures. The ANP structures displayed had a clear structural advantage in bone regeneration, owing to the promotion of cell and tissue migration throughout the scaffolds. In particular, ANP-structured scaffolds, which had highest porosity, interconnectivity, and smallest strut thickness, had a mechanical strength comparable to cancellous bone, formed more new bone, were highly resorbed, resulting in cancellous bone-like bone tissue regeneration at 12 weeks of healing. The results suggest that bone regeneration after the migration of cell and tissue into the entire scaffolds is affected by strut thickness preferentially over porosity and interconnectivity. ANP-structured CO3Ap scaffolds are attractive for bone regeneration.

DOI： 10.1002/jbm.a.37608

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記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

2種の生体吸収性骨補填材、炭酸アパタイト(CO3Ap)とβリン酸三カルシウム(β-TCP)を、インプラント設置も同時に行う歯槽骨増大手術に利用し、その転帰を組織学的に比較した。ビーグル犬12頭(体重8～11kg)を実験に使用した。下顎両側の小臼歯領域に骨欠損(長さ7mm、幅2mm、深さ6mm)を作成しCO3Ap小粒またはβ-TCP小粒で歯槽骨増大処置を施した上でチタン製インプラントを設置した。手術の4、12、24週後に下顎検体を採取してインプラント周囲を組織学的に評価した。β-TCP小粒の大部分は術後早期に消失しており、そのためインプラント周囲の歯槽骨の容積は少なめになっていた。それに対し、CO3Apを適用した群では歯槽骨高さが低下することなく歯槽堤が再建されており、少なくとも術後12週までにはインプラントのほぼ全てのネジ山が新生骨で覆われていた。歯槽堤部分において新生骨形成が認められた百分率を算出する定量評価を行った。その結果、CO3Ap群の方がより高い百分率になっていることが示された。また骨-インプラント接触率に関しても、12週後と24週後にはβ-TCP群よりもCO3Ap群の方が有意に高くなっていた。インプラント設置を同時施行する歯槽骨増大術で臨床使用する目的においてCO3Apは有用であると考えられた。

掲載種別：研究論文（学術雑誌）   出版者・発行元：Bulletin of Materials Science  

Low-crystalline Mg-substituted β-tricalcium phosphate (Mg-β-TCP) block with a foaming structure (foam) was fabricated through a compositional conversion via a dissolution–precipitation reaction using α-tricalcium phosphate (α-TCP) foam as precursors in a solution containing 1.0 mol l−1 MgCl2 and 0.1 mol l−1 NaH2PO4 under hydrothermal conditions at 100°C for 2 days. However, after immersion in the above-mentioned solution, the microstructure of the α-TCP foam consisted of polycrystalline aggregates, which are different from α-TCP foam and appear to have a typical sintered structure. The compressive strength and porosity of the Mg-β-TCP foam were 9.8 ± 1.02 MPa and 55.61 ± 4.13%, respectively. The fabricated Mg-β-TCP foam showed excellent interconnectivity. When the fabricated Mg-β-TCP foam was soaked in a dye solution, the inner structure of the fabricated Mg-β-TCP foam was completely stained. This suggests that the fabricated Mg-β-TCP foam might have excellent tissue penetration and good biocompatibility.

DOI： 10.1007/s12034-023-02981-9

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その他リンク： https://link.springer.com/article/10.1007/s12034-023-02981-9/fulltext.html

記述言語：英語  

DOI： https://doi.org/10.1007/s12034-023-02981-9

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Applied Materials and Interfaces  

The aging population has rapidly driven the demand for bone regeneration. The pore structure of a scaffold is a critical factor that affects its mechanical strength and bone regeneration. Triply periodic minimal surface gyroid structures similar to the trabecular bone structure are considered superior to strut-based lattice structures (e.g., grids) in terms of bone regeneration. However, at this stage, this is only a hypothesis and is not supported by evidence. In this study, we experimentally validated this hypothesis by comparing gyroid and grid scaffolds composed of carbonate apatite. The gyroid scaffolds possessed compressive strength approximately 1.6-fold higher than that of the grid scaffolds because the gyroid structure prevented stress concentration, whereas the grid structure could not. The porosity of gyroid scaffolds was higher than that of the grid scaffolds; however, porosity and compressive strength generally have a trade-off relationship. Moreover, the gyroid scaffolds formed more than twice the amount of bone as grid scaffolds in a critical-sized bone defect in rabbit femur condyles. This favorable bone regeneration using gyroid scaffolds was attributed to the high permeability (i.e., larger volume of macropores or porosity) and curvature profile of the gyroid structure. Thus, this study validated the conventional hypothesis using in vivo experiments and revealed factors that led to this hypothetical outcome. The findings of this study are expected to contribute to the development of scaffolds that can achieve early bone regeneration without sacrificing the mechanical strength.

DOI： 10.1021/acsami.3c06263

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Computational and Structural Biotechnology Journal  

Synthetic bone grafts are in high demand owing to increased age-related bone disorders in the global aging population. Here, we report fabrication of gear-shaped granules (G-GRNs) for rapid bone healing. G-GRNs possessed six protrusions and a hexagonal macropore in the granular center. These were composed of carbonate apatite, i.e., bone mineral, microspheres with ∼1-μm micropores in the spaces between the microspheres. G-GRNs formed new bone and blood vessels (both on the granular surface and within the macropores) 4 weeks after implantation in the rabbit femur defects. The formed bone structure was similar to that of cancellous bone. The bone percentage in the defect recovered to that in a normal rabbit femur at week-4 post-implantation, and the bone percentage remained constant for the following 8 weeks. Throughout the entire period, the bone percentage in the G-GRN-implanted group was ∼10% higher than that of the group implanted with conventional carbonate apatite granules. Furthermore, a portion of the G-GRNs resorbed at week-4, and resorption continued for the following 8 weeks. Thus, G-GRNs are involved in bone remodeling and are gradually replaced with new bone while maintaining a suitable bone level. These findings provide a basis for the design and fabrication of synthetic bone grafts for achieving rapid bone regeneration.

DOI： 10.1016/j.csbj.2023.03.053

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Materials Au  

In a globally aging society, synthetic bone blocks are in increasing demand. An ideal synthetic bone block fuses early with bone and is replaced with new bone at a suitable speed while withstanding the weight load. Herein, we report carbonate apatite honeycomb (HC) blocks with superior mechanical strength, osteoconductivity, and bioresorbability compared to a clinically used synthetic porous block (control block). Three types of HC blocks were fabricated via the debinding of HC green bodies at 600, 650, and 700 °C and subsequent phosphatization, designated as HC-600, HC-650, and HC-700, respectively. The macropores in these HC blocks uniaxially penetrated the blocks, whereas those in the control block were not interconnected. Consequently, the HC blocks exhibited higher open macroporosities (18%-20%) than the control block (2.3%). In contrast, the microporosity of the control block (46.4%) was higher than those of the HC blocks (19%-30%). The compressive strengths of the HC-600, HC-650, HC-700, and control blocks were 24.7, 43.7, 103.8, and 38.9 MPa, respectively. The HC and control blocks were implanted into load-bearing segmental bone defects of rabbit ulnae. Uniaxial HC macropores enabled faster bone ingrowth than the poorly interconnected macropores in the control block. Microporosity in the HC blocks affected bone formation and osteoclastic resorption over a period of 24 weeks. The resorption of HC-650 corresponded to new bone formation; therefore, new bone with strength equal to that of the original bone bridged the separated bones. Thus, the HC blocks achieved the reconstruction of segmental bone defects while withstanding the weight load. The findings of this study contribute to the design and development of synthetic bone blocks for reconstructing segmental defects.

DOI： 10.1021/acsmaterialsau.3c00008

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Biomedical Materials Research - Part B Applied Biomaterials  

The composition of carbonate apatite (CO3Ap) aids bone regeneration. Other features, such as porosity and pore interconnectivity of artificial bone, also govern bone regeneration. In general, a trade-off exists between the porosity and mechanical strength of artificial bone. Therefore, this suggests that the interconnected pores in the ant-nest-type porous (ANP) structure of artificial bone accelerate bone regeneration by minimizing the sacrifice of mechanical strength. The unique structure of polyurethane foam has the potential to endow CO3Ap with an ANP structure without forming excess pores. This study investigated the efficacy of polyurethane foam as a porogen in providing ANP structure to CO3Ap artificial bone. The polyurethane foam was completely decomposed by sintering and the resulting CO3Ap displayed ANP structure with a compressive strength of approximately 15 MPa. Furthermore, in vivo experiments revealed that the migration of cells and tissues into the interior of CO3Ap through the interconnected pores accelerated bone regeneration in the ANP-structured CO3Ap. Thus, this indicates that using polyurethane foam as a porogen endows the CO3Ap artificial bone with an ANP structure that accelerates bone regeneration.

DOI： 10.1002/jbm.b.35173

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jbm.b.35173

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Materials  

Apatite cement (AC), which has excellent osteoconductive ability, and alpha-tricalcium phosphate (α-TCP), which can be used for bone replacement, are useful bone substitute materials. The objective of this study was to clarify the physical properties and antimicrobial release ability of antibiotic-loaded AC/α-TCP composites in vitro. Gentamicin-loaded, rapid setting AC/α-TCP composites were prepared in 2 mixing ratios (10:3 and 10:6). The cement paste of AC/α-TCP composites was prepared in a plastic mold and dried in a thermostatic chamber at 37 °C and 100% relative humidity for 24 h. A diametral tensile strength test, powder X-ray diffraction analysis, and gentamicin release test were performed. The diametral tensile strengths of the AC/α-TCP composites were significantly less than that of AC alone. Powder X-ray diffraction patterns exhibited the characteristic peaks of hydroxyapatite in the AC/α-TCP composites and gentamicin-loaded AC/α-TCP composites. The concentration of the released gentamicin was maintained above the minimum inhibitory concentration of Staphylococcus aureus until Day 30 in both the gentamicin-loaded AC/α-TCP composites (10:3 and 10:6). Our results suggest that a gentamicin-loaded AC/α-TCP composite has potential as a drug delivery system. Further study is essential to investigate the antimicrobial activity and safety of the gentamicin-loaded AC/α-TCP composites in animal models.

DOI： 10.3390/ma16030995

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oral Science International  

Aim: This study histologically compared two bioresorbable bone substitutes with different composition, carbonate apatite (CO3Ap) and beta-tricalcium phosphate (β-TCP), through alveolar bone augmentation with simultaneous titanium implant placement in beagle dogs. Methods: Bone defects (length 7 mm, width 2 mm, and depth 6 mm) were created bilaterally at mandibular premolar sites and augmented with either CO3Ap or β-TCP granules after titanium implant installation. The specimens with the surrounding tissue were harvested from the mandible at 4, 12, and 24 weeks postoperatively, and histological evaluation was performed. Results: Most β-TCP granules dissolved in early stages postoperatively, resulting in a lower volume of alveolar bone surrounding the titanium implant. By contrast, in the case of CO3Ap group, the alveolar ridge was reconstructed without reducing the alveolar bone height, and almost all implant threads were covered with new bone by at least 12 weeks postoperatively. Quantitatively, the CO3Ap group showed a significantly higher percentage of new bone formation in the alveolar ridge portion at all follow-ups. Additionally, it demonstrated a significantly higher bone-to-implant contact ratio than that of the β-TCP group at 12 and 24 weeks after implantation (70.8 ± 5.6% vs. 29.3 ± 16.4% and 54.8 ± 6.9% vs. 41.8 ± 2.2%, respectively). Conclusion: In conclusion, based on the superior outcomes noted in this study, CO3Ap is useful for clinical use in alveolar bone augmentation with simultaneous implant placement.

DOI： 10.1002/osi2.1170

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/osi2.1170

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Materials Science: Materials in Medicine  

Carbonate apatite (CO3Ap) granules are useful as a bone substitute because they can be remodeled to new natural bone in a manner that conforms to the bone remodeling process. However, reconstructing large bone defects using CO3Ap granules is difficult because of their granular shape. Therefore, we fabricated CO3Ap honeycomb blocks (HCBs) with continuous unidirectional pores. We aimed to elucidate the tissue response and availability of CO3Ap HCBs in the reconstruction of rabbit mandibular bone defects after marginal mandibulectomy. The percentages of the remaining CO3Ap area and calcified bone area (newly formed bone) were estimated from the histological images. CO3Ap area was 49.1 ± 4.9%, 30.3 ± 3.5%, and 25.5 ± 8.8%, whereas newly formed bone area was 3.0 ± 0.6%, 24.3 ± 3.3%, and 34.7 ± 4.8% at 4, 8, and 12 weeks, respectively, after implantation. Thus, CO3Ap HCBs were gradually resorbed and replaced by new bone. The newly formed bone penetrated most of the pores in the CO3Ap HCBs at 12 weeks after implantation. By contrast, the granulation tissue scarcely invaded the CO3Ap HCBs. Some osteoclasts invaded the wall of CO3Ap HCBs, making resorption pits. Furthermore, many osteoblasts were found on the newly formed bone, indicating ongoing bone remodeling. Blood vessels were also formed inside most of the pores in the CO3Ap HCBs. These findings suggest that CO3Ap HCBs have good osteoconductivity and can be used for the reconstruction of large mandibular bone defects. Graphical Abstract: [Figure not available: see fulltext.].

DOI： 10.1007/s10856-022-06710-2

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その他リンク： https://link.springer.com/article/10.1007/s10856-022-06710-2/fulltext.html

記述言語：英語  

DOI： https://doi.org/10.1007/s10856-022-06710-2

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Advanced Research  

Introduction: Cases of intractable dental implant require vertical bone augmentation; however, the predicted bone height and volume are difficult to obtain. In vertical bone augmentation, the contact surface between the scaffold and the bone is limited to the bottom face of the scaffold. Furthermore, the strength decrease caused by scaffold resorption leads to collapse of the augmented site, leading to a decrease in the bone volume and height. Objectives: To promote bone ingrowth, we fabricated carbonate apatite (i.e., bone mineral) honeycomb (HC) scaffolds with uniaxial channels vertically penetrating the scaffold. Furthermore, we controlled the scaffold resorption rate, eventually the endurability for compression, and the bone height and volume by controlling the strut thickness. Methods: The channel aperture was controlled to be 230–260 μm to promote bone ingrowth. Furthermore, the strut thicknesses of the HC scaffolds were adjusted to 100, 200, and 300 μm to control the scaffold resorption; these scaffolds were designated as HC100, HC200, and HC300, respectively. Results: At 4 weeks post-implantation on rabbit calvarium, all scaffolds had already vertically augmented new bone close to the top surface of the scaffold. In the following 8 weeks, the height and amount of new bone in all scaffolds increased. Notably, HC300 was resorbed synchronously with new bone formation, allowing it to endure the compression from the fasciae for 12 weeks post-implantation. Furthermore, HC300 formed larger-diameter blood vessels than those of HC100 and HC200. Conclusion: The HC scaffolds surpassed the various combined scaffolds and growth factors or stem cells in the ability for vertical bone augmentation. Thus, the HC structure is inherently suitable for vertical bone augmentation. Notably, the HC scaffolds with 300-μm-thick struts enhanced both new bone formation and angiogenesis. This study revealed a structurally suitable design for achieving an outstanding outcome in vertical bone augmentation.

DOI： 10.1016/j.jare.2021.12.010

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bioengineering  

Synthetic scaffolds with the ability to prevent fibrous tissue penetration and promote bone augmentation may realize guided bone regeneration without the use of a barrier membrane for dental implantation. Here, we fabricated two types of honeycomb scaffolds of carbonate apatite, a bone mineral analog, whose channel apertures were square (HC-S) and rectangular (HC-R). The side lengths of the HC-Ss and HC-Rs were 265.8 ± 8.9; 817.7 ± 2.4 and 267.1 ± 5.2 μm, respectively. We placed cylindrical HC-Ss and HC-Rs on the rabbit calvaria. At 4 weeks post-implantation, the HC-Ss prevented fibrous tissue penetration from the top face via the channels, which allowed the new bone to reach the top of the scaffold from the bottom face or the calvarium. In contrast, in the HC-Rs, fibrous tissues filled the channels in the top region. At 12 weeks post-implantation, the HC-Ss were partially replaced with new bone. In the top region of the HC-Rs, although new bone had formed, fibrous tissue remained. According to the findings here and in our previous study, the longer side length rather than the shorter side length of a rectangular scaffold channel aperture is the dominant factor that affects fibrous tissue penetration and new bone augmentation. Furthermore, even though channel aperture areas are similar, bone and fibrous tissue ingrowths are different when the aperture shapes are different.

DOI： 10.3390/bioengineering9110627

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Ceramics International  

Carbonate apatite (CO3Ap) artificial bone is fabricated in an aqueous solution using calcium carbonate as a precursor. CO3Ap has attracted attention because it demonstrates high osteoconductivity and can replace a damaged bone based on the bone remodeling process. This study aims to compare vaterite and calcite, which are metastable and stable polymorphs of calcium carbonate, respectively, as precursors. When the vaterite granules, which have higher solubility and consist of smaller crystals than calcite, prepared from calcium oxide granules were immersed in disodium hydrogen phosphate solution, the compositional transformation to CO3Ap was quicker than that of calcite. Based on the investigations on rabbit femurs, it was observed that the remodeling of CO3Ap to a new bone was faster when vaterite was used as a precursor compared to when calcite was used as a precursor. It is concluded that vaterite can be a better precursor than calcite for CO3Ap artificial bone fabrication.

DOI： 10.1016/j.ceramint.2022.05.336

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記述言語：英語  

DOI： https://doi.org/10.1016/j.ceramint.2022.05.336

記述言語：英語  

DOI： https://doi.org/10.1002/jbm.b.35173

記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Nano  

Although studies on scaffolds for tissue generation have mainly focused on the chemical composition and pore structure, the effects of scaffold shape have been overlooked. Scaffold shape determines the scaffold surface area (SA) at the single-scaffold level (i.e., microscopic effects), although it also affects the amount of interscaffold space in the tissue defect at the whole-system level (i.e., macroscopic effects). To clarify these microscopic and macroscopic effects, this study reports the osteogenesis abilities of three types of carbonate apatite granular scaffolds with different shapes, namely, irregularly shaped dense granules (DGs) and two types of honeycomb granules (HCGs) with seven hexagonal channels (∼255 μm in length between opposite sides). The HCGs possessed either 12 protuberances (∼75 μm in length) or no protuberances. Protuberances increased the SA of each granule by 3.24 mm2while also widening interscaffold spaces and increasing the space percentage in the defect by ∼7.6%. Interscaffold spaces were lower in DGs than HCGs. On DGs, new bone formed only on the surface, whereas on HCGs, bone simultaneously formed on the surface and in intrascaffold channels. Interestingly, HCGs without protuberances formed approximately 30% more new bone than those with protuberances. Thus, even tiny protuberances on the scaffold surface can affect the percentage of interscaffold space, thereby exerting dominant effects on osteogenesis. Our findings demonstrate that bone regeneration can be improved by considering macroscopic shape effects beyond the microscopic effects of the scaffold.

DOI： 10.1021/acsnano.2c03776

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記述言語：英語   出版者・発行元：Journal of Biomedical Materials Research - Part A  

The present study investigated the osteoclast differentiation potential and paracrine effects of osteoclasts on osteoblast differentiation when the cells were cultured directly on two bone substitutes (BSs): deproteinized bovine bone mineral (DBBM) and carbonate apatite (CO3Ap). Human primary osteoclasts cultured on the BSs were assessed by tartrate-resistant acid phosphatase (TRAP) and actin ring staining. Thereafter, the mRNA levels of osteoclastic differentiation markers were quantified by real-time PCR. Osteoblast behaviors in response to conditioned media collected from osteoclast cultures were investigated. Interestingly, mature osteoclasts were occasionally observed on the surface of the CO3Ap granules, whereas very few and small osteoclasts were observed on DBBM. Similarly, real-time PCR analysis showed higher mRNA levels of osteoclast markers, including cathepsin K and TRAP, in the cells cultured on CO3Ap than in those cultured on DBBM. Furthermore, compared to DBBM, CO3Ap promoted osteoblast differentiation in human primary osteoblasts, whereas few paracrine effects of osteoclasts cultured with either BS were observed on the osteoblast differentiation potential. These limited results showed that CO3Ap provided a favorable surface for osteoclast differentiation, as well as osteoblasts, compared to DBBM in vitro.

DOI： 10.1002/jbm.a.37392

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記述言語：英語  

DOI： https://doi.org/10.1021/acsnano.2c03776

掲載種別：研究論文（学術雑誌）   出版者・発行元：Ceramics International  

Beta-tricalcium phosphate (βTCP) granules are commonly used as an artificial bone graft material. Meanwhile, the surface morphology of the bone graft is an important factor for cellular response. In this study, feasibility study on surface morphology regulation of βTCP bone graft for enhancing cellular response were investigated. The regulation was achieved on the basis of a multistep heating process. Briefly, initial heat treatment of βTCP granules at 1300 °C for 12 h resulted in fabrication of alpha-tricalcium phosphate (αTCP) granules with interconnected micropores. In the second heat treatment, exposure of αTCP granules to 100% relative humidity at 100 °C resulted in partial hydrolysis of αTCP, leading to the fabrication of needle-like calcium-deficient hydroxyapatite (cdHAp) crystals on the αTCP surface. After the third heat treatment at 1100 °C, both cdHAp and αTCP converted back to βTCP, and interconnected micropores with a roughened surface structure were formed. In vitro cell evaluation demonstrated that βTCP granules obtained by the series of heat treatments exhibited 24 times higher cell proliferation at day 9, and four times higher alkaline phosphatase activity compared with untreated βTCP granules. Therefore, we concluded that regulation of surface morphology by a series of heat treatments is useful for improving cellular response to βTCP bone grafting materials.

DOI： 10.1016/j.ceramint.2022.02.200

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Regenerative Biomaterials  

Porous architecture in bone substitutes, notably the interconnectivity of pores, is a critical factor for bone ingrowth. However, controlling the pore interconnectivity while maintaining the microarchitecture has not yet been achieved using conventional methods, such as sintering. Herein, we fabricated a porous block using the crystal growth of calcium sulfate dihydrate, and controlled the pore interconnectivity by limiting the region of crystal growth. The calcium sulfate dihydrate blocks were transformed to bone apatite, carbonate apatite (CO3Ap) through dissolution-precipitation reactions. Thus, CO3Ap blocks with 15% and 30% interconnected pore volumes were obtained while maintaining the microarchitecture: They were designated as CO3Ap-15 and CO3Ap-30, respectively. At 4 weeks after implantation in a rabbit femur defect, new bone formed throughout CO3Ap-30, whereas little bone was formed in the center region of CO3Ap-15. At 12 weeks after implantation, a large portion of CO3Ap-30 was replaced with new bone and the boundary with the host bone became blurred. In contrast, CO3Ap-15 remained in the defect and the boundary with the host bone was still clear. Thus, the interconnected pores promote bone ingrowth, followed by replacement of the material with new bone. These findings provide a useful guide for designing bone substitutes for rapid bone regeneration.

DOI： 10.1093/rb/rbac010

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その他リンク： https://academic.oup.com/rb/article-pdf/doi/10.1093/rb/rbac010/43399674/rbac010.pdf

記述言語：英語  

DOI： https://doi.org/10.1002/jbm.a.37392

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biomaterials Advances  

Osteomyelitis is a potentially devastating inflammatory bone disease that leads to bone destruction and loss. Treatment of osteomyelitis requires the removal of residual bacteria as well as osteogenesis with angiogenesis at the site of treatment. Use of an appropriate amount of copper (Cu) in treatment scaffolds may achieve these goals without the risk of toxicity. In this study, the surface of the carbonate apatite honeycomb scaffold was functionalized with Cu through a dissolution–precipitation reaction. The resulting scaffolds retained the honeycomb structure after immersion in CuCl2 solution, and Cu was precipitated on the surface as libethenite [Cu2(OH)PO4]. The surface Cu concentration was controlled by the concentration of the CuCl2 solution. Scaffolds with a surface Cu concentration of 23.8 wt% exhibited antibacterial and cytotoxic effects, whereas those with concentrations of ≤4.6 wt% exerted antibacterial effects without negatively affecting the cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like cells. Furthermore, scaffolds with a surface Cu concentration of 4.6 wt% Cu inhibited bacterial growth for at least 28 days and displayed proangiogenic and pro-osteogenic activities in vivo. These data confirm the success in functionalizing scaffolds with Cu that may be utilized as an innovative osteomyelitis therapy.

DOI： 10.1016/j.bioadv.2022.212751

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記述言語：英語  

記述言語：英語  

DOI： https://doi.org/10.3389/fbioe.2022.825831

記述言語：日本語  

DOI： https://doi.org/10.1016/j.mtbio.2022.100247

記述言語：英語  

DOI： https://doi.org/10.1016/j.bioadv.2022.212751

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Bioengineering and Biotechnology  

The reconstruction of critical-sized segmental bone defects is a key challenge in orthopedics because of its intractability despite technological advancements. To overcome this challenge, scaffolds that promote rapid bone ingrowth and subsequent bone replacement are necessary. In this study, we fabricated three types of carbonate apatite honeycomb (HC) scaffolds with uniaxial channels bridging the stumps of a host bone. These HC scaffolds possessed different channel and micropore volumes. The HC scaffolds were implanted into the defects of rabbit ulnar shafts to evaluate the effects of channels and micropores on bone reconstruction. Four weeks postoperatively, the HC scaffolds with a larger channel volume promoted bone ingrowth compared to that with a larger micropore volume. In contrast, 12 weeks postoperatively, the HC scaffolds with a larger volume of the micropores rather than the channels promoted the scaffold resorption by osteoclasts and bone formation. Thus, the channels affected bone ingrowth in the early stage, and micropores affected scaffold resorption and bone formation in the middle stage. Furthermore, 12 weeks postoperatively, the HC scaffolds with large volumes of both channels and micropores formed a significantly larger amount of new bone than that attained using HC scaffolds with either large volume of channels or micropores, thereby bridging the host bone stumps. The findings of this study provide guidance for designing the pore structure of scaffolds.

DOI： 10.3389/fbioe.2022.825831

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Materials Today Bio  

Granular porous calcium phosphate scaffolds are used for bone regeneration in dentistry. However, in conventional granules, the macropore interconnectivity is poor and has varying size. Herein, we developed a productive method for fabricating carbonate apatite honeycomb granules with uniformly sized macropores based on extrusion molding. Each honeycomb granule possesses three hexagonal macropores of ∼290 ​μm along its diagonal. Owing to these macropores, honeycomb granules simultaneously formed new and mature bone and blood vessels in both the interior and exterior of the granules at 4 weeks after implantation. The honeycomb granules are useful for achieving rapid osteogenesis and angiogenesis.

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記述言語：英語   出版者・発行元：(一社)日本歯科理工学会  

歯科領域で骨充填材として使われる炭酸アパタイト(CA)粒子が、骨欠損領域から流出してしまうという問題について検討するため、同粒子を混和させる酸性リン酸溶液のpHとイオン成分が硬化時間に及ぼす影響を評価した。CA粒子には300～600μmサイズのものを調製して用いた。対イオンにナトリウムイオンを採用した場合、沈着するリン酸二カルシウム二水和物(DCPD)の量が少なくなり、pHを上げると硬化する能力が失われた。他方でカルシウムイオン(Ca2+)を対イオンとした時にはDCPD沈着量が多くなり、高いpH値であっても硬化可能であることが観察された。こうした結果から、CA粒子配合セメントを製造するためには、酸性リン酸溶液中のCa2+の存在が鍵となることが示唆された。

掲載種別：研究論文（学術雑誌）   出版者・発行元：Materials and Design  

The use of scaffolds with pores ranging from macroscale to nanoscale (i.e., multiscale pores), is an effective strategy to achieve favorable bone regeneration. Here, we report the fabrication of multiscale porous scaffolds (MPSs) and evaluate the effects of macropores (>100 μm) and micropores (<10 μm) on bone regeneration in the early to medium term. MPSs were constructed from interconnecting carbonate apatite honeycomb granules. The uniaxial macropores penetrating the honeycomb granules linked the gaps among the granules, creating an interconnected macroporous architecture. MPSs with different proportions of macropores and micropores were implanted into rabbit femurs. In an early stage, macropores played a crucial role in promoting new bone formation. In the medium term, micropores, rather than macropores, were the dominant factor affecting the replacement of MPSs with new bone. Notably, micropores of 100 nm to 10 μm primarily promoted MPS resorption by osteoclasts, stimulating secondary osteogenesis. Our findings demonstrated that pore size distribution, rather than porosity, was crucial for osteogenesis in the early-to-medium term. Although conventional scaffold development sacrifices mechanical strength to improve bone formation, our findings indicate that optimizing the pore size distribution is a promising strategy to develop scaffolds that satisfy the requirements of both osteogenesis and mechanical strength.

DOI： 10.1016/j.matdes.2022.110468

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Ceramics International  

Metastable vaterite blocks are expected to show high reactivity. However, they have not been reported to date. In this study, the feasibility of fabricating an artificial vaterite block was investigated by exposing a Ca(OH)2 compact to CO2 under several conditions. Under a 100% H2O atmosphere, a calcite block was formed within three days. Under a 100% methanol atmosphere, no carbonation was observed for seven days. Under 90% methanol without atmospheric flow, a vaterite block containing 5 mass% of unreacted Ca(OH)2 and 3 mass% of calcite was formed after 24 h. On day 7, it was transformed into a block with 70 mass% of calcite, 27 mass% of vaterite, and 3 mass% of unreacted Ca(OH)2. By contrast, under 90% methanol with atmospheric flow to remove the accumulated H2O in the compact, a pure CaCO3 block of 98 mass% vaterite and 2 mass% calcite was formed on day 3. Therefore, the regulation of the amount of H2O is important for fabricating vaterite blocks. Porosimetry measurements revealed that the calcite block fabricated under 90% methanol without atmospheric flow demonstrated a pore size profile closer to that of the vaterite block than that of the calcite block fabricated under 100% H2O atmosphere because the vaterite with small spherical crystals was formed initially before its transformation to calcite.

DOI： 10.1016/j.ceramint.2021.10.206

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Biomedical Materials Research - Part A  

The porous architecture of artificial bones plays a pivotal role in bone ingrowth. Although salt leaching methods produce predictable porous architectures, their application in the low-temperature fabrication of ceramics remains a challenge. Carbonate apatite (CO3Ap) blocks with three ranges of pore sizes: 100–200, 200–400, and 400–600 μm, were fabricated from CaCO3 blocks with embedded Na2HPO4 crystals as a porogen and accelerator for CaCO3-to-CO3Ap conversion. CaCO3 blocks were obtained from Ca(OH)2 compacts with Na2HPO4 by CO2 flow at 100% humidity. When carbonated under 100% water humidity, the dissolution of Na2HPO4 and the formation of hydroxyapatite were observed. Using 90% methanol and 10% water were beneficial in avoiding the Na2HPO4 consumption and generating the metastable CaCO3 vaterite, which was rapidly converted into CO3Ap in a Na2HPO4 solution in 7 days. For the histological evaluation, the CO3Ap blocks were implanted in rabbit femur defects. Four weeks after implantation, new bone was formed at the edges of the blocks. After 12 weeks, new bone was observed in the central areas of the material. Notably, CO3Ap blocks with pore sizes of 100–200 μm were the most effective, exhibiting approximately 23% new bone area. This study sheds new light on the fabrication of tailored porous blocks and provides a useful guide for designing artificial bones.

DOI： 10.1002/jbm.a.37374

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jbm.a.37374

記述言語：英語  

DOI： https://doi.org/10.1016/j.ceramint.2021.10.206

記述言語：英語  

DOI： https://doi.org/10.1016/j.ceramint.2022.02.200

記述言語：英語  

DOI： https://doi.org/10.1093/rb/rbac010

記述言語：英語   出版者・発行元：Journal of Tissue Engineering and Regenerative Medicine  

Carbonate apatite (CO3Ap), an inorganic component of human bone, has been clinically applied as an artificial bone substitute. In this study, the effects of the CO3 content in CO3Ap on the replacement by new bone were studied by fabricating CO3Ap granules containing 0.9–8.3 wt% of CO3. The dissolution rate of CO3Ap in a weak acidic solution, mimicking the Howship's lacunae, was rapid for the CO3Ap granules containing a larger amount of CO3. Histological analyses demonstrated the rapid resorption in CO3Ap and replacement by natural bone tissue when the CO3 content was increased. Therefore, the CO3 content in CO3Ap is a key factor that influences the replacement of the bone tissue.

DOI： 10.1002/term.3270

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Infectious Diseases  

Fracture-related infections require both treatments for bacteria removal and bone reconstruction. The use of combined broad-spectrum antibacterial silver compounds and artificial bone with high osteogenic activity is considered to be an effective strategy for achieving these treatments in one surgery. However, silver compounds are toxic for living tissues even at low concentrations. Herein, we investigated the no-observed-effect level (NOEL) of silver phosphate (Ag3PO4) in a bone substitute composed of carbonate apatite (CO3Ap), a bone mineral, using in vitro and in vivo experiments. In vitro experiments demonstrated that the CO3Ap artificial bone containing ≥0.1 wt % Ag3PO4 exerted antibacterial effects against Staphylococcus epidermidis, while those containing ≤0.3 wt % Ag3PO4 did not affect cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like MC3T3-E1 cells. In vivo experiments demonstrated that the CO3Ap artificial bone containing ≤0.3 wt % Ag3PO4 replaced a new bone to the same levels as those without Ag3PO4 4 weeks after implantation into the bone defect of the rabbit femur condyle. However, the CO3Ap artificial bone containing 0.3 wt % Ag3PO4 caused an inflammatory reaction, whereas those containing ≤0.1 wt % Ag3PO4 did not. Thus, both bone regeneration and infection control without any adverse effects were achieved using the CO3Ap artificial bone containing 0.1 wt % Ag3PO4, indicating that the NOEL of Ag3PO4 was 0.1 wt %. Our results provide an effective strategy for the treatments of fracture-related infections.

DOI： 10.1021/acsinfecdis.1c00480

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記述言語：英語  

DOI： https://doi.org/10.1021/acsami.1c20204

記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Applied Materials and Interfaces  

Surgical site infection (SSI) is a severe complication associated with orthopedic bone reconstruction. For both infection prevention and bone regeneration, the framework surface of osteoconductive and bioresorbable scaffolds must be locally modified by minimum antibacterial substances, without sacrificing the osteoconductivity of the scaffold framework. In this study, we fabricated antibacterial honeycomb scaffolds by replacing carbonate apatite, which is the main component of the scaffold, with silver phosphate locally on the scaffold surface via dissolution–precipitation reactions. When the silver content was 9.9 × 10–4 wt %, the honeycomb scaffolds showed antibacterial activity without cytotoxicity and allowed cell proliferation, differentiation, and mineralization. Furthermore, the antibacterial honeycomb scaffolds perfectly prevented bacterial infection in vivo in the presence of methicillin-resistant Staphylococcus aureus, formed new bone at 2 weeks after surgery, and were gradually replaced with a new bone. Thus, the antibacterial honeycomb scaffolds achieved both infection prevention and bone regeneration. In contrast, severe infection symptoms, including abscess formation, osteolytic lesions, and inflammation, occurred 2 weeks after surgery when honeycomb scaffolds without silver phosphate modification were implanted. Nevertheless, the unmodified honeycomb scaffolds eliminated bacteria and necrotic bone through their scaffold channels, resulting in symptom improvement and bone formation. These results suggest that the honeycomb structure is inherently effective in hindering bacterial growth. This novel insight may contribute to the development of antibacterial scaffolds. Moreover, our modification method is useful for providing antibacterial activity to various biomaterials.

DOI： 10.1021/acsami.1c20204

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ceramics International  

Granular-shaped carbonate apatite (CO3Ap) bone substitute has demonstrated good clinical results, especially in the bone augmentation procedure, because it has high osteoconductivity and can be replaced by a new bone. This study aimed to evaluate the potential usefulness of CO3Ap bone substitute for alveolar ridge preservation of beagle dogs during the 9-week follow-up period after surgery. Reconstruction of extraction sockets with CO3Ap granules (CO3Ap group) allowed approximately 1.0 mm higher alveolar bone height than that with a blood clot (control group) at 4 and 9 weeks after surgery. Additionally, the measured area at the buccal aspect of the alveolar bone in the CO3Ap group was approximately 2 mm2 larger than that in the control group at 4 and 9 weeks after surgery. Continuity from the buccal side to palatal side of the alveolar bone was restored, maintaining its contour at 4 weeks after surgery. The amount of bony tissue, especially the amount of mature bone, in the alveolar part was statistically larger than that of control group at 9 weeks after surgery even though complete replacement of CO3Ap granules with new bone was not observed within 9 weeks. In conclusion, CO3Ap granules have good potential for alveolar ridge preservation.

DOI： 10.1016/j.ceramint.2021.09.260

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

DOI： https://doi.org/10.1016/j.ceramint.2021.09.260

記述言語：英語  

DOI： https://doi.org/10.1016/j.jare.2021.12.010

DOI： 10.1002/nano.202000283

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記述言語：日本語   出版者・発行元：国立研究開発法人 科学技術振興機構  

※本記事に抄録はありません。

DOI： 10.1241/sangakukanjournal.18.1_13

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出版者・発行元：Key Engineering Materials  

This study concerns the evaluation of the bioactivity and cells response of strontium (Sr) doped sol-gel derived S53P4 bioglass due to Sr induced osteoblast. Moreover it prevents in-vitro osteoclastic activity and is clinically used as osteoporosis treatment. The different amount of Sr was doped into the S53P4 bioglass formulation (53.82%SiO2-1.72%P2O5-22.64%Na2O-(21.76-x)%CaO-x%SrO) (x=0, 3 and 5 mol %) and synthesized via sol-gel method. These samples were denoted as 0Sr, 3Sr and 5Sr respectively. After soaking in Hank's balanced salt solution (HBSS) for 7 and 14 days, the apatite formation was examined using X-ray powder diffraction (XRD) and scanning electron microscope (SEM) techniques. Proliferation and alkaline phosphatase activity were evaluated using osteoblastic cell line MC3T3-E1. The XRD and SEM findings confirmed the hydroxyapatite (HA) structure on the bioglass surface after soaking. More intense HA peaks were observed in 3Sr specimen on 7 day while in 5Sr specimen on 14 day. Meanwhile, 3Sr specimen showed the highest cells proliferation and significant difference in alkaline phosphatase (ALP) activity than 0Sr and 5Sr. As a result, this finding indicates that S53P4 bioglass with 3 mol % SrO (3Sr) is a good candidate for bone tissue engineering because it allows for optimum cell proliferation and ALP activity while also having a high bioactivity efficiency.

DOI： 10.4028/p-6y8965

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掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Series in Biomaterials Science and Engineering  

Elder people tend to be bedridden by accidents accompanied by bone fractures. Therefore, a solution that maintains the quality of life for patients by providing early recovery of wounded or damaged hard tissues supported by high-functional bone substitutes would be ideal. In this chapter, we will describe the successful fabrication of novel bone substitutes that is similar to natural bone from the perspective of inorganic component, crystallinity, and bioresorbability. These properties are essential if natural bones damaged through falls are fully replaced by artificially synthesized bone substitutes. We will also discuss the concept, synthesis route, and the introduction of interconnected pores into the structures of bone substitutes.

DOI： 10.1007/978-981-16-7439-6_7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.matlet.2021.130716

記述言語：英語  

DOI： https://doi.org/10.1021/acsinfecdis.1c00480

記述言語：英語  

DOI： https://doi.org/10.1002/term.3270

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.ceramint.2021.06.252

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ma14195760

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人　日本歯科理工学会  

Carbonate apatite (CO3Ap) is an inorganic component of bone and replaces by natural bone after implantation into the bone defect. Because of this unique characteristic, CO3Ap granules have been used in the dental field. However, washing out of granules from the bone defect area is an issue. The aim of this study was to set CO3Ap granules by mixing CO3Ap granules with acidic phosphate solutions and evaluate the influence of the pH and ion components of the solutions. When Na+ was the counter ion, the amount of precipitated dicalcium phosphate dihydrate (DCPD) was small and the setting ability disappeared with increasing pH of the solutions. Alternatively, when the counter ion was Ca2+, the amount of precipitated DCPD was high and the setting ability was observed even at high pH. These results suggest the presence of Ca2+ in the acidic phosphate solution is a key for fabricating CO3Ap granular cement.

DOI： 10.4012/dmj.2021-211

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/jcp.30336

記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ceramics International  

Carbonate apatite (CO3Ap) artificial bone has attracted much attention due to its high osteoconductivity and replacement to bone. CO3Ap is an inorganic component of bone, and has been fabricated by compositional transformation through a dissolution–precipitation reaction in Na2HPO4 solution using calcium carbonate as a precursor. In this study, the effects of the CO32− concentration in the Na2HPO4 solution on the CO3Ap fabrication reaction and the properties of the fabricated CO3Ap were investigated. The rate of the compositional transformation became faster, and more CO3 containing CO3Ap was fabricated using CO32− concentrated in Na2HPO4 solution. The crystal shape of CO3Ap changed from scale-like to hexagonal crystals. In addition, the crystallite size increased with increasing CO32− concentration in the Na2HPO4 solution. These changes lead to larger pores (≥0.02 μm) and decreased number of small pores (<0.02 μm) according to the CO3 content in CO3Ap, even though the total pore volume remained the same. These findings indicate that the CO32− concentration in Na2HPO4 solution is an important factor for the CO3Ap fabrication reaction and affects the properties of the fabricated CO3Ap.

DOI： 10.1016/j.ceramint.2021.09.188

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1039/D1MA00698C

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1021/acsabm.1c00533

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.ceramint.2021.03.324

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Recently, biofilm formation caused by bacterial adhesion and colonization has been recognized as the major cause of failure in orthopedic and dental implant surgeries. In this study, a customized micro-arc oxidation (MAO) treatment technique was developed to obtain desirable antibacterial properties on Ti surfaces. The two-step MAO treatment was applied in the fabrication of specimens with Ag and with/without Zn in their surface oxide layer. In order to simulate practical usage, surface analyses and immersion tests were performed to evaluate the incorporation of Ag and Zn into the resulting oxide layer and ion release behavior, respectively. Additionally, the antibacterial properties of the specimens after long-term immersion in physiological saline were evaluated using Gram-negative facultative anaerobic bacteria. The MAO-treated specimens containing Ag and Zn exhibited excellent antibacterial properties against Escherichia coli, which were sustained even after 6 months of immersion in physiological saline to simulate practical usage. Moreover, the Ag ions released from the surface oxide indicate the antibacterial properties of the specimen in the early stage, while the release of the corrosion products of Zn demonstrates its antibacterial properties in the later stage.

DOI： 10.3390/coatings11070798

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/14686996.2021.1947120

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Although the channel architecture of a scaffold is critical for bone regeneration, little is known for the channel direction. In this study, four types of carbonate apatite cylindrical scaffolds; scaffolds with biaxial channels (VH-scaffold), with uniaxial vertical channels (V-scaffold), with uniaxial horizontal channels (H-scaffold), and without channels (N-scaffold), were implanted in a rabbit femur defect for 4 and 12 weeks. Although the largest bone was formed 4 weeks post-implantation in the VH-scaffold, newly formed bone disappeared with the scaffold after 12 weeks. Thus, biaxial channels resulted in the rapid dissolution of the scaffold and were counterproductive in long-term bone regeneration. The V-scaffold that had channels connected to the periosteum was gradually resorbed throughout 12 weeks post-implantation. The percentage of mineralized bone in the V-scaffolds was equal to that in the natural bone. The resorption and bone percentage of H-scaffolds that had no channels connected to the periosteum were slower and lower, respectively, than those of V-scaffolds. Thus, channels should be connected to the periosteum to achieve smooth replacement by the new bone. In the N-scaffold, much less bone was formed inside the scaffold. This study contributes to providing a design guide for scaffold development in bone engineering.

DOI： 10.1016/j.matdes.2021.109686

記述言語：英語  

DOI： https://doi.org/10.1016/j.matdes.2021.109686

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4012/dmj.2020-188

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The purpose of this study was to evaluate the surface modification of calcium ions on roughened titanium as a surface treatment of dental implants for cell attachment, growth, and initial bacterial adhesion. When a surface-roughened, pure titanium disk was immersed in a calcium chloride solution (100 mM) containing 20 ppm ozone for 24 h at 25ºC, calcium was detected on the surface by X-ray photoelectron spectroscopy. The calcium-modified, roughened titanium disk had a significantly greater concentration of the initially adhered cells as well as cells cultured over 7 days compared with titanium disks without surface modification. Furthermore, the initial bacterial adhesion on the calcium-ozone treated titanium disk was statistically less than on a pure titanium disk or titanium disk treated without ozone. Dissolved ozone was useful for modifying the surface of roughened titanium with calcium ions and the surface modification may be applicable for dental implants.

DOI： 10.4012/dmj.2020-224

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1002/nano.202000283

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.ceramint.2021.01.017

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of the present study was to assess the duration of dentin tubule occlusion by the calcium phosphate precipitation (CPP) method in the vital teeth of beagle dogs. Vital teeth were treated using the CPP method, potassium oxalate, or a bonding agent (Liner bond II) after cavity preparation and acid etching. The dentin tubules of all groups, except for the bonding agent, opened more widely with time in the absence of plaque control. Dentin tubules treated with the CPP method were open and no precipitate remained in the absence of plaque control. Differences were observed in dentin tubule occlusion when plaque control was achieved by daily tooth brushing. The majority of dentin tubules were occluded with an apatitic precipitate seven days after the CPP method with plaque control. The present results demonstrated that the CPP method is useful with proper plaque control.

DOI： 10.4012/dmj.2020-372

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1002/sia.6900

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1002/jbm.a.37157

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1088/2053-1591/abe018

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1021/acsabm.0c01279

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.ceramint.2020.05.076

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1039/D0TB01498B

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/admi.202000636

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.mtla.2020.100801

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi:10.2109/jcersj2.20059

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.msec.2020.110918

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.mencom.2020.07.037

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.msec.2020.110848

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.jssc.2020.121202

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Carbonate apatite (CO₃Ap) granules are known to show good osteoconductivity and replaced to new bone. On the other hand, it is well known that a porous structure allows bone tissue to penetrate its pores, and the optimal pore size for bone ingrowth is dependent on the composition and structure of the scaffold material. Therefore, the aim of this study was to fabricate various porous CO₃Ap granules through a two-step dissolution–precipitation reaction using CaSO₄ as a precursor and 30-, 50-, 120-, and 205-μm diameter microfibers as porogen and to find the optimal pore size of CO₃Ap. Porous CO₃Ap granules were successfully fabricated with pore size 8.2–18.7% smaller than the size of the original fiber porogen. Two weeks after the reconstruction of rabbit calvarial bone defects using porous CO₃Ap granules, the largest amount of mature bone was seen to be formed inside the pores of CO₃Ap (120) [porous CO₃Ap granules made using 120-μm microfiber] followed by CO₃Ap (50) and CO₃Ap (30). At 4 and 8 weeks, no statistically significant difference was observed based on the pore size, even though largest amount of mature bone was formed in case of CO₃Ap (120). It is concluded, therefore, that the optimal pore size of the CO₃Ap is that of CO₃Ap (120), which is 85 μm.

DOI： 10.1002/jbm.a.36850

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1021/acsabm.0c01176

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Material composition and porous structure are important factors in the formation and maturation of newly formed bone and replacement of materials by new bone. Conventional bone graft materials often lack suitability for bone generation because of the complexity of their macroporous structures, which can interfere with the penetration of cells related to bone remodeling and angiogenesis in the materials. In the present study, carbonate apatite (CO₃Ap), hydroxyapatite (HAp), and β-tricalcium phosphate (TCP) honeycomb granules (HCGs) with uniformly sized macropores (â&circ;¼115 μm) were fabricated. These HCG macropores were arranged in a regular fashion and penetrated straight into the granules. They were implanted into a rabbit femur defect for further evaluation. In the CO₃Ap HCG implantation group, mature bone formed within CO₃Ap HCG macropores by 4 weeks after grafting, and a large portion of CO₃Ap HCGs was replaced by new bone at 12 weeks. By contrast, in the β-TCP HCG implantation group, new bone was not always formed in the regions after β-TCP HCG disappearance, and immature bone was present within β-TCP HCG macropores even after 12 weeks. HAp HCGs were not resorbed, and their macropores were filled with immature bone. The area of mature bone in the CO₃Ap HCG implantation group was 3.3 and 1.6 times higher at 4 weeks and 2.2 and 1.7 times higher at 12 weeks compared with the HAp and β-TCP HCG implantation groups, respectively. Furthermore, the degrees of bone maturation for CO₃Ap, HAp, and β-TCP HCGs were 100, 34, and 64% at 4 weeks, and 100, 54, and 69% at 12 weeks, respectively. Thus, the composition of the HCGs affected bone formation and maturation.

DOI： 10.1021/acsabm.0c00060

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Medical pure titanium (Ti) exhibits excellent mechanical properties and chemical stability in clinical use, but its initial osteointegration period is often postponed due to the bioinert nature of the Ti surface. Roughening and bioactive material coating of Ti implant surfaces are considered effective to enhance the bioactivity of Ti implants. In this study, we evaluated the effects of surface roughening and calcite (CaCO₃) coating of Ti substrates on osteoblastic cell differentiation and growth. We roughened the Ti substrate surface by acid etching, followed by coating with calcite by thermal decomposition of Ca(NO₃)₂ to CaO followed by thermal carbonation of CaO to CaCO₃. The surface topography of roughened Ti substrates (rough Ti) fluctuated, and the arithmetic average of surface roughness (Ra) was 2.2 µm. The rough topography was retained even after calcite coating of rough Ti, and the calcite-coated Ti (calcite-Ti) has an Ra of 2.0 µm. The tensile adhesive and shear adhesive strengths between calcite coating and Ti surface in calcite–Ti were 56.6 ± 16.1 and 10.1 ± 1.39 MPa, respectively. The biological properties and response of calcite–Ti were evaluated in vitro using a pre-osteoblastic cell line (MC3T3-E1). Observation of cell morphology by scanning electron microscopy and immunofluorescence staining revealed that MC3T3-E1 cells attached favorably to the surface with polygonal and filopodial extensions on calcite–Ti. The combination of roughening and calcite coating of the Ti substrate surface significantly increased cell proliferation at 1, 3, and 7 days of incubation. Furthermore, the relative alkaline phosphatase activity of calcite–Ti was higher than that of untreated Ti substrates (smooth Ti) and rough Ti after incubation for 7 days. Thus, the combined surface roughening and calcite coating of Ti substrates promoted MC3T3-E1 differentiation, whereas roughening alone was not effective.

DOI： 10.1177/0885328219883765

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Calcium phosphate (CP)-based biomaterials, especially nanostructured ones, show a high biocompatibility and increased biological properties. The coatings composed of stoichiometric hydroxyapatite have been extensively used to improve integration of metallic implants in the host bone. However, these coatings exhibited several drawbacks that limited their successful application. It was concluded in numerous articles that the sol-gel derived coatings can undergo cracking and delamination and are scarcely uniform. In this review article the recent advances on the sol-gel synthesis of different phosphate coatings and thin films are summarized. The attention is paid to coatings and thin films of calcium hydroxyapatite (CHAp), other phosphates, bioglasses and different composite materials. The state of the art, limitations, potentialities, open challenges, and the future scenarios for the application of CP bioceramics are highlighted in this study.

DOI： 10.6001/chemija.v31i1.4169

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Surface wettability is attracting increasing attention as an important factor that affects the cell/tissue responses of implant materials. Time-dependent hydrocarbon adsorption on the titanium (Ti) implant surface has been reported to decrease the surface hydrophilicity by adsorption of hydrocarbon contaminants from the atmosphere and dramatically decrease the osseointegration over time. In this study, we found that ozone-gas-mediated removal of hydrocarbon contaminants and introduction of –OH groups significantly increased the surface hydrophilicity of acid-etched Ti without changing the original surface topography. Ozone-gas-treated Ti dramatically enhanced osteogenic differentiation of mesenchymal stem cells, as evidenced by greater cell proliferation, alkaline phosphatase activity, and bone-like nodule formation compared with original Ti.

DOI： 10.1016/j.matlet.2019.127168

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this study for the synthesis of silver-doped calcium hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂:Ag; CHAp:Ag) an environmentally friendly aqueous sol-gel processing has been suggested. The sinterability and morphological properties of silver-activated calcium hydroxyapatite were investigated in the present study. The calcium hydroxyapatite doped with high concentration of silver (up to 10 wt %) has been prepared. This simple synthetic approach offers a feasible way to obtain highly homogeneous silver-doped CHAp bioceramics with possible application in medicine. The synthesis products were characterized using X-ray powder diffraction (XRD) analysis, infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The content of Ca, P and Ag in the synthesis products was determined by SEM (EDX).

DOI： 10.1016/j.micromeso.2019.109806

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of this study is to investigate the response of cells and bacteria on Sr, Ag, and Sr + Ag doped S53P4 sol-gel bioglass. In this study, 3 mol% of SrO and 1 mol% of Ag₂O were selected as doping for single and multiple doped S53P4 sol-gel bioglass. These doped specimens were denoted as BG, BG-3S, BG-1A, and BG-3S1A throughout the study. Cell study showed that the BG-3S1A specimen exhibited the highest proliferation of MC3T3-E1 osteoblast-like cells, ALP activity, and bone nodule formation in comparison with other specimens. Meanwhile, antibacterial study of the BG-3S1A specimen showed relatively similar antibacterial responses towards Escherichia coli and Staphylococcus aureus in comparison with the BG-1A specimen. Therefore, these findings proved that by combining appropriate amount of Sr and Ag doping ions into S53P4 bioglass composition, cellular proliferation and antibacterial response could be stimulated, which could benefit patients who suffer from bacteria-infected bone defect diseases.

DOI： 10.1016/j.ceramint.2020.04.094

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this review article the available results about application of sol–gel synthesis method for the preparation of different calcium phosphates and composite materials are summarized. The attention is paid to calcium phosphate-containing compounds which show the biological properties and could be used as potential phosphate bioceramics in medicine. It was demonstrated that the sol–gel synthesis method is a powerful tool for the synthesis of calcium hydroxyapatite and other phosphates, and different calcium phosphate-based composites at mild synthetic conditions resulted in high reproducibility, high phase purity, and desired morphology. Thus, the sol–gel synthesis method enables the researchers to develop biomaterials with superior features in terms of biomedical applications.

DOI： 10.1007/s10971-020-05245-8

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Biomedical applications of poly(ether ether ketone) (PEEK) are hindered by its inherent bioinertness and lack of osseointegration capability. In the present study, to enhance osteogenic activity and, hence, the osseointegration capability of PEEK, we proposed a strategy of combined phosphate and calcium surface-functionalization, in which ozone-gas treatment and wet chemistry were used for introduction of hydroxyl groups and modification of phosphate and/or calcium, respectively. Surface functionalization significantly elevated the surface hydrophilicity without changing the surface roughness or topography. The cell study demonstrated that immobilization of phosphate or calcium increased the osteogenesis of rat mesenchymal stem cells compared with bare PEEK, including cell proliferation, alkaline phosphatase activity, and bone-like nodule formation. Interestingly, further enhancement was observed for samples co-immobilized with phosphate and calcium. Furthermore, in the animal study, phosphate and calcium co-functionalized PEEK demonstrated significantly enhanced osseointegration, as revealed by a greater direct bone-to-implant contact ratio and bond strength between the bone and implant than unfunctionalized and phosphate-functionalized PEEK, which paves the way for the orthopedic and dental application of PEEK.

DOI： 10.3390/ijms21010198

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Beta-tricalcium phosphate granular cement (β-TCP GC), consisting of β-TCP granules and an acidic calcium phosphate (Ca-P) solution, shows promise in the reconstruction of bone defects as it sets to form interconnected porous structures, that is, β-TCP granules are bridged with dicalcium phosphate dihydrate (DCPD) crystals. In this study, the effects of acidic Ca-P solution concentration (0–600 mmol/L) on the setting reaction and tissue response to β-TCP GC were investigated. The β-TCP GC set upon mixing with its liquid phase, based on the formation of DCPD crystals, which bridged β-TCP granules to one another. Diametral tensile strength of the set β-TCP GC was relatively the same, at ∼0.6 MPa, when the Ca-P concentration was 20–600 mmol/L. Due to the setting ability, reconstruction of the rat's calvarial bone defect using β-TCP GC with 20, 200, and 600 mmol/L Ca-P solution was much easier compared to that with β-TCP granules without setting ability. Four weeks after the reconstruction, the amount of new bone was the same, ∼17% in both β-TCP GC and β-TCP granules groups. Cellular response to β-TCP granules and β-TCP GC using the 20 mmol/L acidic Ca-P solution was almost the same. However, β-TCP GC using the 200 and 600 mmol/L acidic Ca-P solution showed a more severe inflammatory reaction. It is concluded, therefore, that β-TCP GC, using the 20 mmol/L acidic Ca-P solution, is recommended as this concentration allows surgical techniques to be performed easily and provides good mechanical strength, and the similar cellular response to β-TCP granules.

DOI： 10.1002/jbm.b.34361

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the present study cerium substitution effects in the sol-gel derived yttrium iron garnet (Ce:Y₃Fe₅O₁₂, Ce:YIG) have been investigated. To avoid formation of CeO₂ as side phase the samples were prepared under different conditions. Synthesis of Ce:YIG in the reducing atmosphere, however, showed the formation of perovskite YFeO₃ as dominant phase. Mixed-metal cerium substituted yttrium aluminium iron garnets (Ce:Y₃Al_5-xFe_xO₁₂, Ce:YIAG) were synthesized in the form of bulk and coating. Single phase Y_2.925Ce_0.075Al_5-xFe_xO₁₂ (x = 1, 2, 3, and 4) were successfully synthesized using the same sol-gel processing route. The garnet thin films with composition of Y_2.925Ce_0.075Al₁Fe₄O₁₂ were fabricated on a quartz substrate by dip-coating technique. The phase purity and structural features of obtained powders and thin films were evaluated using X-ray diffraction (XRD) analysis. The surface composition was determined by X-ray photoelectron spectroscopy (XPS). The morphology of synthesis products was investigated by scanning electron microscopy (SEM).

DOI： 10.1016/j.solidstatesciences.2019.106065

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Titainum (Ti) implants have been successfully used in orthopaedic and dental surgery. However, poor early bone tissue integration is still a common cause of implant failure. This could be modulated by improving the material bonding or adhesion directly to the bone by surface roughening and/or a bioresorbable and osteoconductive coating. In this study, we report on the biological behaviours of the Ti substrate with modified surface roughness and/or a calcium carbonate (CaCO₃) coating. The roughened Ti surface was prepared using an acid etching reaction, and the CaCO₃ coating on the substrates was synthesized by the hydrothermal treatment of Ti in calcium citrate complexes. This study demonstrates that surface roughening of Ti alone does not improve the biological response of the MC3T3-E1 cells, but a CaCO₃ coating on the smooth Ti surface increases cell responses, and these effects are further enhanced by the combination of coating a roughened Ti surface with CaCO₃. The larger the cell area, the greater the cell proliferation and increased bone-like nodule formation were observed on the CaCO₃ coating of the roughened Ti surface. This observation was also supported by a higher ALP value. The cell behaviours found in the current study further support the development of CaCO₃ coatings towards clinical application.

DOI： 10.1088/1748-605X/ab6939

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5051/jpis.2019.49.6.382

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hematopoietic stem cells form blood cells in bone marrow and reside in niches. Artificial environments that conserve these niches may generate bone marrow. Osteogenesis, angiogenesis, and material resorption must be regulated to create these environments. These processes are controlled by material composition and macro- and microporous structures. Here, three blocks with different micropore structures are fabricated. Carbonate apatite has nearly the same composition as natural human bone and their honeycomb structure facilitates cell penetration and survival. In samples with high microporosity, endosteum-like tissues such as sinusoids form in areas of material resorption and high local calcium concentration. These conditions resemble environments conducive to niche maintenance. Bone marrow–like tissues and megakaryocytes are successfully generated in this environment. Micropore structure is the most critical factor in bone marrow formation; however, the influences of material composition and macropore structure must also be considered. The results of this study may help develop treatments for bone marrow–related diseases and elucidate the components and functions of the hematopoietic stem cell niche.

DOI： 10.1002/adbi.201900140

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ma12233997

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jbm.a.36842

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the present study the transition metal substitution effects in Mg_3-xM_x/Al₁ (M = Mn, Co, Ni, Cu, Zn) layered double hydroxides (LDHs) were investigated. For the synthesis of the mentioned compounds a newly developed sol-gel synthesis method has been applied. It was demonstrated that different amounts of Mn, Co, Ni, Cu and Zn could be introduced to the sol-gel derived LDHs without destroying the layered structure. The synthesis products were characterized using X-ray powder diffraction (XRD) analysis, infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The specific surface area of differently substituted Mg_3-xM_x/Al₁ LDH specimens was also estimated. The synthesized LDHs could be tested for different medical applications and could be used as precursor material for the preparation of nanostructured mixed-metal oxides with a variety of useful properties.

DOI： 10.1016/j.matchemphys.2019.121863

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jbm.b.34492

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Calcium carbonate (CaCO₃) and particularly its stable phase, calcite, is of great geological significance in the deep carbon cycle since CaCO₃ from biomineralized shells and corals form sedimentary rocks. Calcite also attracts attention in medical science and pharmacy as a primary or intermediate component in biomaterials because it possesses excellent biocompatibility along with suitable physicochemical properties. Calcite blocks have already been used during surgical procedures as a bone substitute for reconstructing bone defects formed by diseases and injury. When producing CaCO₃ biomaterials and bioceramics, in particular, in vivo control of the size and polymorphic nature of CaCO₃ is required. In this study, we investigated the effects of PO₄ on calcite formation during the phase conversion of calcium sulfate anhydrate (CaSO₄, CSA), which is sometimes used as a starting material for bone substitutes because of its suitable setting ability. CSA powder was immersed in 2 mol/L Na₂CO₃ solution containing a range of PO₄ concentrations (0-60 mmol/L) at 40 °C for 3 days. The treated samples were investigated by X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray fluorescence spectroscopy, and thermal analysis. In addition, the fine structures of the treated samples were observed by field-emission scanning electron microscopy, and the specific surface area was measured. We found that PO₄, which is universally present in vivo, can modulate the calcite crystal size during calcite formation. A fluorescence study and calcite crystal growth experiments indicated that PO₄ adsorbs tightly onto the surface of calcite, inhibiting crystal growth. In the presence of high PO₄ concentrations, vaterite is formed along with calcite, and the appearance and stability of the CaCO₃ polymorphs can be controlled by adjusting the PO₄ concentration. These findings have implications for medical science and pharmacology, along with mineralogy and geochemistry.

DOI： 10.2138/am-2019-7015

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Synthetic scaffolds exhibiting bone repair ability equal to that of autogenous bone are required in the fields of orthopedics and dentistry. A suitable synthetic bone graft substitute should induce osteogenic differentiation of mesenchymal stem cells, osteogenesis, and angiogenesis. In this study, three types of honeycomb blocks (HCBs), composed of hydroxyapatite (HAp), β-tricalcium phosphate (TCP), and carbonate apatite (CO₃Ap), were fabricated, and the effects of HCB composition on bone formation and maturation were investigated. The HC structure was selected to promote cell penetration and tissue ingrowth. HAp and β-TCP HCBs were fabricated by extrusion molding followed by sintering. The CO₃Ap HCBs were fabricated by extrusion molding followed by sintering and dissolution-precipitation reactions. These HCBs had similar macroporous structures: all harbored uniformly distributed macropores (∼160 ​μm) that were regularly arrayed and penetrated the blocks unidirectionally. Moreover, the volumes of macropores were nearly equal (∼0.15 ​cm³/g). The compressive strengths of CO₃Ap, HAp, and β-TCP HCBs were 22.8 ​± ​3.5, 34.2 ​± ​3.3, and 24.4 ​± ​2.4 ​MPa, respectively. Owing to the honeycomb-type macroporous structure, the compressive strengths of these HCBs were higher than those of commercial scaffolds with intricate three-dimensional or unidirectional macroporous structure. Notably, bone maturation was markedly faster in CO₃Ap HCB grafting than in β-TCP and HAp HCB grafting, and the mature bone area percentages for CO₃Ap HCBs at postsurgery weeks 4 and 12 were 14.3- and 4.3-fold higher and 7.5- and 1.4-fold higher than those for HAp and β-TCP HCBs, respectively. The differences in bone maturation and formation were probably caused by the disparity in concentrations of calcium ions surrounding the HCBs, which were dictated by the inherent material resorption behavior and mechanism; generally, CO₃Ap is resorbed only by osteoclastic resorption, HAp is not resorbed, and β-TCP is rapidly dissolved even in the absence of osteoclasts. Besides the composition, the microporous structure of HC struts, inevitably generated during the formation of HCBs of various compositions, may contribute to the differences in bone maturation and formation.

DOI： 10.1016/j.mtbio.2019.100031

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.msec.2019.03.106

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Artificial bone substitutes that can solve the problems associated with autogenous bone grafts are essential. In this study, macroporous carbonate apatite (CO₃Ap) granules with the same composition as natural bone were implanted into distal epiphysis defects in rabbit femurs. Material resorption and bone regeneration were then evaluated. The macroporous granules were obtained by extruding honeycomb (HC) structure rods containing calcium hydroxide, pulverizing the rods to granules, carbonating them to calcite, and converting them from calcite to CO₃Ap. Notably, the HC-type macropores fully penetrated and spanned their diameters of the CO₃Ap granules in one direction, as well as being regularly arranged and uniformly sized (120 μm). They facilitated cell penetration into the granules and the induction of angiogenesis. As a result, bone remodeling occurred simultaneously within the granules and on the granule surfaces. Furthermore, the granules were gradually resorbed and replaced by bone. Thus, introducing HC-type macropores into granules is an effective approach for promoting bone regeneration.

DOI： 10.1016/j.ceramint.2019.05.042

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Synthetic calcium deficient hydroxyapatite (CDHA, with the formula Ca₉(HPO₄)(PO₄)₅OH) is a promising material which could be potentially used in biomedicine. The aim of this study was to develop a simple and cost-effective synthesis route for the preparation of low crystalline CDHA granules. A method based on an incessant dissolution-precipitation reaction eventually resulting in a solid and shaped material consisting of the desired phase was utilized. The calcium sulphate hemihydrate was selected as the starting material. The synthesis products obtained were characterized by Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM). The monophasic calcium deficient hydroxyapatite granules of about 300–350 μm in diameter were synthesized by three slightly different preparative approaches at 70 °C temperature and compared. Independently of the composition of the raw granules synthesized ones were composed of low crystalline an apatitic phase. The granules were calcium deficient as contained HPO₄ ²⁻ group in their structure. It was demonstrated that the addition of (NH₄)H₂PO₄ or (NH₄)₂HPO₄ into the raw granules could promote the growth of the CDHA crystallites. SEM revealed that the microstructure of synthesized materials was influenced by the chemical composition of the raw granules. Chemical composition and presence of no an X-ray amorphous phase in obtained samples was confirmed by reheating the obtained granules at 800 °C to get monophasic β-TCP. Our work provides a novel and simple approach to produce CDHA granules for various applications.

DOI： 10.1016/j.ceramint.2019.05.072

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this study, for the synthesis of calcium hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂; CHAp), an environmentally-friendly water-based sol–gel chemistry approach using food products as calcium and phosphorus precursors has been developed. In the sol–gel processing, the food products having the greatest calcium and phosphorus concentrations and the calculated calcium and phosphorus molar ratio closest to Ca/P = 1.67 were selected as starting materials (hard cheese “Dziugas”, preserved Atlantic sardines in oil, low-fat yogurt “Dobilas”, and pumpkin seeds). The synthesis products were investigated by thermal analysis (TG/DTG-DSC), infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD) analysis, and scanning electron microscopy (SEM). The content of Ca and P in the food products was determined by means of ICP-OES. [Figure not available: see fulltext.].

DOI： 10.1007/s10971-019-05020-4

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ceramint.2019.03.174

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.joms.2018.11.026

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Carbonate apatite (CO ₃ Ap) block can be used as a bone substitute because it can be remodeled to new natural bone in a manner conforming with the bone remodeling process. Among the many porous structures available, honeycomb (HC) structure is advantageous for rapid replacement of CO ₃ Ap to bone. In this study, the feasibility to fabricate a CO ₃ Ap HC was studied, along with its initial tissue response in rabbit femur bone defect. First, a mixture of Ca(OH) ₂ and a wax-based binder was extruded from a HC mold. Then the fabricated HC was heated for binder removal and carbonation at 450°C in a mixed O ₂ –CO ₂ atmosphere, forming a CaCO ₃ HC. When the CaCO ₃ HC was immersed in 1 mol/L Na ₃ PO ₄ solution at 80°C for 7 days, its composition changed from CaCO ₃ to CO ₃ Ap, maintaining the structure of the original CaCO ₃ HC. Compressive strengths of the CaCO ₃ and CO ₃ Ap HCs were 65.2 ± 7.4 MPa and 88.7 ± 4.7 MPa, respectively. When the rabbit femur bone defect was reconstructed with the CO ₃ Ap HC, new bone penetrated the CO ₃ Ap HC completely. Osteoclasts and osteoblasts were found on the surface of the newly formed bone and osteocytes were also found in the newly formed bone, indicating ongoing bone remodeling. Furthermore, blood vessels were formed inside the pores of CO ₃ Ap HC. Therefore, CO ₃ Ap HC has good potential as an ideal bone substitute.

DOI： 10.1002/jbm.a.36640

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sol-gel derived calcium hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂; CHA) thin films were deposited on stainless steel substrates with transverse and longitudinal patterned roughness employing a spin-coating technique. Each layer in the preparation of CHA multilayers was separately annealed at 850 °C in air. Fabricated CHA coatings were placed in simulated body fluid (SBF) for 2, 3, and 4 weeks and investigated after withdrawal. For the evaluation of obtained and treated with SBF coatings, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), X-ray diffraction (XRD) analysis, Raman spectroscopy, XPS spectroscopy, scanning electron microscopy (SEM) analysis, and contact angle measurements were used. The tribological properties of the CHA coatings were also investigated in this study.

DOI： 10.3390/COATINGS9050334

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jbm.b.34117

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hydrophilicity of apatite cement was increased after O3 gas treatment on apatite cement (AC) powder. It results on the improvement of the handling and mechanical properties of set AC. Behavior of osteoblastic cells to O3-treated set AC was evaluated including initial cell attachment, morphology of the attached cells and proliferation using rat bone marrow cell (RBM). Cells’ response to the set AC was the same regardless of O3 treatment. The cells well attached and spread with filopodial extensions even over the O3-treated set AC specimens. The rates of cell proliferation on set AC were also the same regardless of O3 treatment. The result indicated O3 treatment of AC powder would not affect to the osteoblast cell response of set AC.

DOI： 10.4028/www.scientific.net/JBBBE.43.124

記述言語：英語   掲載種別：研究論文（その他学術会議資料等）  

Statement of Purpose: Recently, AB-type carbonate apatite (CO₃Ap) bone substitute block was fabricated by just immersing a precursor, CaCO₃ block, in sodium phosphate solution through dissolution-precipitation reaction. CO₃Ap block showed higher osteoconductivity and replaced to bone. It should be noted that not only composition but also structure plays important role for the replacement to bone since porous structure allows cells penetration interior to the bone substitute. One of the interesting porous structures is honeycomb. In this study, CO₃Ap honeycomb was fabricated, and evaluated its usefulness as vertical bone augmentation device using rabbits as experimental animals.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Poly(ether ether ketone) (PEEK) has emerged as an alternative endosseous material to metal implants mainly because of its lack of allergic sensitivity and radiolucency, while maintaining similar mechanical properties with bone. However, a disadvantage of PEEK is its weak osseointegration ability compared with metal implants. To overcome this, we prepared a phosphate group-modified PEEK by plasma treatment and subsequent phosphorylation reaction. Plasma treatment and phosphate modification of PEEK changed its hydrophobic surface to a hydrophilic surface while maintaining the original surface topography and roughness. Phosphate modification increased the bioactivity of rat bone marrow stromal cells (BMSCs), including proliferation, alkaline phosphatase activity, and bone-like nodule formation; however, this effect was negligible in plasma-treated PEEK. In addition, phosphate modification attenuated the phenotypic polarization of lipopolysaccharide-primed RAW264.7 macrophages to an inflammatory phenotype, based on the finding that macrophages on phosphate-modified PEEK produced decreased levels of the inflammatory cytokine and increased levels of the anti-inflammatory cytokine. Finally, in an animal study, phosphate-modified PEEK exhibited a doubled pullout force from the femur bone cavity compared with bare PEEK. Thus, we conclude that phosphate modification can significantly improves the implant-bone bonding strength of PEEK by enhancing BMSCs activity and reducing excessive inflammation.

DOI： 10.1016/j.colsurfb.2018.09.032

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Development of dental plaque begins with the adhesion of salivary bacteria to the acquired pellicle covering the tooth surface. In this study, we collected in vivo dental plaque formed on hydroxyapatite disks for 6 h from 74 young adults and identified initial colonizing taxa based on full-length 16S rRNA gene sequences. A long-read, single-molecule sequencer, PacBio Sequel, provided 100,109 high-quality full-length 16S rRNA gene sequence reads from the early plaque microbiota, which were assigned to 90 oral bacterial taxa. The microbiota obtained from every individual mostly comprised the 21 predominant taxa with the maximum relative abundance of over 10% (95.8 6.2%, mean SD), which included Streptococcus species as well as nonstreptococcal species. A hierarchical cluster analysis of their relative abundance distribution suggested three major patterns of microbiota compositions: a Streptococcus mitis/Streptococcus sp. HMT-423-dominant profile, a Neisseria sicca/Neisseria flava/Neisseria mucosadominant profile, and a complex profile with high diversity. No notable variations in the community structures were associated with the dental caries status, although the total bacterial amounts were larger in the subjects with a high number of caries-experienced teeth (8) than in those with no or a low number of caries-experienced teeth. Our results revealed the bacterial taxa primarily involved in early plaque formation on hydroxyapatite disks in young adults. IMPORTANCE Selective attachment of salivary bacteria to the tooth surface is an initial and repetitive phase in dental plaque development. We employed full-length 16S rRNA gene sequence analysis with a high taxonomic resolution using a third-generation sequencer, PacBio Sequel, to determine the bacterial composition during early plaque formation in 74 young adults accurately and in detail. The results revealed 21 bacterial taxa primarily involved in early plaque formation on hydroxyapatite disks in young adults, which include several streptococcal species as well as nonstreptococcal species, such as Neisseria sicca/N. flava/N. mucosa and Rothia dentocariosa. Given that no notable variations in the microbiota composition were associated with the dental caries status, the maturation process, rather than the specific bacterial species that are the initial colonizers, is likely to play an important role in the development of dysbiotic microbiota associated with dental caries.

DOI： 10.1128/mSystems.00360-19

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Silver (Ag) has the antibacterial property and can be easily introduced in glasses and glass-ceramics. In this research, the effect of Ag addition on the apatite formation of sol-gel derived new composition bioactive glass (BG) (55%SiO₂ - 4% P₂O₅ -22%Na₂O - (19-x) %CaO -x% Ag₂O) (x=0, 5 and 8%) were investigated. The synthesized Ag doped BG samples were treated in Hank's Balanced Salt Solution (HBSS) for 14 days to study the bioactivity. The achieved samples were evaluated by X-ray powder diffraction (XRD) and Scanning electron microscope (SEM). The XRD spectra clearly show diffraction peaks of bone-like hydroxyapatite (HAp) for all samples after immersion in HBSS. However, the more intense of HAp peak at 32° was detected in Ag(5%) and Ag(8%) BGs compared with undoped BG. All glass samples are bioactive but BG with 8 wt% of Ag₂O exhibited more apatite than the samples containing 5 wt% of Ag₂O, as seen in SEM images. After 14 days immersion, full coverage of apatite in cluster crystal form on the Ag(8) glass surface was observed.

DOI： 10.1016/j.matpr.2019.06.385

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bioactive glasses and glass-ceramics were applied in bone fix applications, dental applications as well as in tissue engineering. New S50P4 glass with a composition of SiO₂-Na₂O-CaO-P₂O₅ in the quaternary system with different aging time (3, 5 and 7 days) was prepared by sol-gel method. XRD results indicate that the crystalline patterns in gel-derived glass aged for 3 days exhibit high intensity peaks compare to samples aged for 5 and 7 days. In FTIR spectra, the intensity of the crystalline silicate and phosphate phases were decreased with an increase aging time.

DOI： 10.1016/j.matpr.2019.06.033

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bone is not composed of hydroxyapatite (HAp), but of carbonate apatite (CO₃Ap). Although the decomposition of CO₃Ap begins at around 400°C, and thus, the fabrication of CO₃Ap blocks by sintering is difficult, CO₃Ap blocks have recently been fabricated via a dissolutionprecipitation reaction in Na₂HPO₄ solution using a CaCO₃ block as a precursor. Compared to sintered HAp, which is not resorbed by osteoclasts, CO₃Ap is resorbed by osteoclasts. Furthermore, CO₃Ap upregulates the differentiation of osteoblasts. Therefore, CO₃Ap can be used as a replacement for bones with regards to the so-called bone remodeling process. Clinical trials have confirmed the safety and usefulness of CO₃Ap granules, including the replacement of CO₃Ap granules to new bone. In Dec 2017, CO₃Ap was approved as an artificial bone substitute by the Pharmaceuticals and Medical Devices Agency. CO₃Ap granules can be used for all dental and maxillofacial surgeries, including the bone reconstruction aimed for dental implantation.

DOI： 10.2109/jcersj2.19042

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.surfcoat.2018.09.050

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: The aim of this present study was to investigate the effect of setting atmosphere on replacement of apatite cement with new bone both in vitro and in vivo. Material and methods: Apatite cement consisting of an equimolar mixture of tetracalcium phosphate and anhydrous dicalcium phosphate was mixed with distilled water and allowed to set at 37 °C and 100% relative humidity under 0%_, 5%, and 100% CO₂ atmospheres. X-Ray diffraction and Fourier Transform Infrared Spectroscopy were employed to confirm the carbonate apatite formation. Micro-CT and histological evaluation was made at 1 and 6 month(s) using twelve 10-week-old specific-pathogen-free male Wistar rats. Results: B-type carbonate apatite was found when the apatite cement was set under 100% CO₂ and 5% CO₂. More carbonate apatite was formed in the case of 100% CO₂ when compared with 5% CO₂, and none was formed under 0% CO₂. Interestingly, unreacted tetracalcium phosphate was significant when apatite cement was set under 0% CO₂, indicating the formation of Ca-deficient hydroxyapatite. When a bone defect of rat tibia was reconstructed in these conditions of apatite cement and sintered hydroxyapatite, replacement of the apatite cement was confirmed 6 months after implantation, whereas no replacement was observed in the case of sintered hydroxyapatite. The amount of replacement of apatite cement with bone was greater, on the order of 100% CO₂ and 5% CO₂, followed by 0% CO₂. Conclusion: The results obtained in the present study demonstrated that setting atmosphere clearly plays an important role in the replacement of set apatite cement with bone.

DOI： 10.1016/j.jmbbm.2018.08.021

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.matlet.2018.12.093

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-018-35313-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jssc.2018.08.008

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Calcium sulfate dihydrate (CSD) has been used as a material for bone augmentation for many years. However, rapid resorption of CSD sometimes results in insufficient formation of new bone. In the present study, the feasibility of fabricating apatite-coated CSD (Ap/CSD) was studied, with the hypothesis that the apatite coating would reduce the rate of CSD resorption and enhance the osteoconductivity. To prepare Ap/CSD granules, 300–400 µm CSD granules were immersed in Na₂HPO₄ solution at 20 °C or 60 °C, resulting in granules coated with apatitic precipitates. Granules were analyzed by microscopy and x-ray diffraction, and the dissolution rate into pH 7.5 Tris-HCl buffer solution was measured. Osteoconductivity was assessed by the release of calcium ions, and their ability to stimulate new bone formation was examined through reconstruction of rabbit distal femur bone defects. It was found that the apatite coating resulted in increased osteoconduction and a decreased dissolution rate compared with bare CSD granules. When rabbit distal femur bone defect was reconstructed with Ap/CSD, CSD and sintered hydroxyapatite (s-HAp), all samples demonstrated an excellent tissue response. Four weeks after surgery, a higher radio opacity was obtained for Ap/CSD when compared with CSD, indicating new bone formation. The s-HAp granules remained and thus, new bone formation was smallest even though s-HAp granules bonded with the bone. Ap/CSD that was fabricated at 60 °C induced greater bone formation than CSD. It is therefore concluded that Ap/CSD has good potential value as a bone augmentation material.

DOI： 10.1016/j.ceramint.2018.08.021

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1177/0885328218808015

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bioactive glasses and glass-ceramics were applied in bone fix applications, dental applications as well as in tissue engineering. In the current study, a new quaternary silicate bioglass S50P4 (50%SiO₂-24.5%Na₂O-21.5%CaO-4%P₂O₅) with different aging time (3, 5 and 7 days) was prepared by sol-gel method. These synthesized glasses were analyzed using X-ray powder diffraction (XRD), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Whereas the bioactivity of the optimized samples were observed through in-vitro test using Hank's Balanced Salt Solution (HBSS) at different soaking time (7 and 14 days). XRD results indicate that the crystalline patterns in gel-derived glass aged for 3 days exhibit stronger peaks compare to samples aged for 5 and 7 days. This could be attributed to the difference of water content inside the gels. Moreover, the peak at 2θ∼33° became sharper and more intense for longer soaking times corresponds to the apatite structure. Besides, in-vitro test shows, the formation of hydroxyl carbonated apatite layer (HCA) with finer grains.

DOI： 10.1088/1742-6596/1082/1/012070

記述言語：英語   掲載種別：研究論文（学術雑誌）  

β-tricalcium phosphate (β-TCP) bone substitutes have been widely used because of its excellent tissue response and good osteoconductivity. However, recent study reported that the osteoconductivity of β-TCP could be enhanced by treating β-TCP surfaces with saturated acidic calcium phosphate solution. In this study, the osteoconductivity of treated β-TCP granule were evaluated using micro-computed tomography (micro-CT) scan technique. The granule specimens were obtained by exposing β-TCP granules with saturated acidic calcium phosphate solution for 10, 30 and 60 mins, respectively. Then, critical bone defect size with dimension of 9 mm were made at rat calvarial, and the defect was reconstructed with 10, 30 and 60 mins treated β-TCP granules and β-TCP granules without treatment as a control. After 2 and 4 weeks implantation, the specimens with the surrounding bone tissue were taken out and examined using micro-CT machine. Based on the cross section of micro-CT images, new bone formations were observed from the edge of the defect towards the center of the bone defect area in all specimens. At 2 weeks, new bone formations were observed for 10 min and 30 min treated β-TCP granules when compared with other specimens. The 30 min treated β-TCP granules showed faster new bone formation rate after 4 weeks implantation. It can be concluded that 30 min treated β-TCP granules revealed the highest osteoconductivity in comparison to the other specimens.

DOI： 10.1088/1742-6596/1082/1/012069

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ma11101993

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10856-018-6162-1

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Carbonate apatite (CO3Ap) is an inorganic component of bone. This study aimed to compare the composition and tissue response to of CO3Ap (CO3Ap-DP) fabricated by the dissolution–precipitation reaction using calcite as a precursor and Bio-Oss®, which is widely used in orthopedic and dental fields as a synthetic bone substitute. X-ray diffraction and Fourier transform infrared results showed that CO3Ap-DP and Bio-Oss® were both B-type carbonate apatite with low crystallinity. The average sizes of CO3Ap-DP and Bio-Oss® granules were 450 ± 58 and 667 ± 168μ m, respectively, and their carbonate contents were 12.1 ± 0.6 and 5.6 ± 0.1 wt%, respectively. CO3Ap-DP had a larger amount of CO3 than Bio-Oss® but higher crystallinity than Bio-Oss®. When a bone defect made at the femur of rabbits was reconstructed with CO3Ap-DP and Bio-Oss®, CO3Ap-DP granules were partially replaced with bone, whereas Bio-Oss® remained at 8 weeks after implantation. CO3Ap-DP granules elicited a significantly larger amount of new bone formation at the cortical bone portion than Bio-Oss® at 4 weeks after the implantation. The results obtained in the present study demonstrated that CO3Ap-DP and Bio-Oss® showed different behavior even though they were both classified as CO3Ap. The CO3 content in CO3Ap played a more important role than the crystallinity of CO3Ap for replacement to bone and high osteoconductivity.

DOI： 10.1007/s10856-018-6129-2

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1088/1748-605X/aad385

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although sintered β-tricalcium phosphate blocks have been used clinically as artificial bone substitutes, the crystallinity of β-tricalcium phosphate, which might dominate biocompatibility, is extremely high. The objective of this study is to evaluate the feasibility of fabricating low-crystallinity β-tricalcium phosphate blocks, which are expected to exhibit good biocompatibility via a dissolution-precipitation reaction of α-tricalcium phosphate blocks as a precursor under hydrothermal conditions at 200°C for 24 h. Although β-tricalcium phosphate is a metastable phase, the presence of Mg2+ in the reaction solution inhibits the formation of its corresponding stable phase and induces β-tricalcium phosphate formation under acidic conditions. It was found that low-crystallinity β-tricalcium phosphate blocks could be fabricated from α-tricalcium phosphate blocks immersed in 1.0 mol/L MgCl2 + 0.1 mol/L NaH2PO4 solution while maintaining the shape of the α-tricalcium phosphate blocks. The crystallite size of the fabricated β-tricalcium phosphate blocks was 42 nm, which was substantially smaller than that of the sintered β-tricalcium phosphate blocks. When the fabricated β-tricalcium phosphate blocks were implanted into bone defects in rabbit femurs, they exhibited excellent tissue responses. In particular, the initial osteoconductivity (two and four weeks) was substantially greater than that of sintered β-tricalcium phosphate blocks.

DOI： 10.1177/0885328218788255

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/term.2742

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Octacalcium phosphate (OCP) has attracted much attention as an artificial bone substitute because of its excellent osteoconductive and bone replacement properties. Although numerous studies have investigated OCP powder fabrication, there are only a few studies on OCP block fabrication. Therefore, in this study, the feasibility of optimizing dicalcium hydrogen phosphate dihydrate (DCPD) blocks, as a precursor for OCP block fabrication, under a pH 6 adjusted acetate buffer solution at 70^◦ C for 2 days was investigated. When a DCPD block was immersed in acetate buffer, the block was partially converted to OCP, with a large amount of dicalcium hydrogen phosphate anhydrate (DCPA), and its macroscopic structure was maintained. When the DCPD block was immersed in a Ca-containing solution, it was converted to mainly hydroxyapatite (HAp) with DCPA. On the other hand, when the DCPD block was immersed in a PO₄-containing solution, the block was converted to OCP, and its macroscopic structure was maintained. In other words, the PO₄-induced calcium phosphate with a Ca/P molar ratio lower than 1.0 may represent an intermediate phase during the compositional transformation from a DCPD block to an OCP block through the dissolution–precipitation reaction.

DOI： 10.3390/cryst8050222

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.3390/cryst8050222

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Poly(ether ether ketone) (PEEK) has emerged as a candidate to replace metal implants because of its satisfactory mechanical properties, radiolucency, and lack of metal allergy. However, PEEK lacks osseointegration ability limiting its clinical applications. To overcome this problem, we prepared PEEK with a micro-rough surface using the sandblast method to modulate its osseointegration property; the sandblast method is simple, cost-effective, and is already applied to clinical metal implants. The surface roughness of the sandblasted PEEK was about 2.3 μm, whereas that of mirror-polished PEEK was 0.06 μm. Rat bone marrow-derived mesenchymal stem cells (RMSCs) showed higher proliferation, osteocalcin (OC) expression and bone-like nodule formation on micro-roughened PEEK compared with those cultured on mirror-polished PEEK, suggesting that micro-roughening facilitated RMSCs proliferation and differentiation. The micro-roughened surface slightly mitigated secretion of inflammatory C-C motif chemokine 2 (CCL-2) from lipopolysaccharide (LPS)-stimulated macrophages, but not of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6). Finally, to compare osseointegration, specimens were implanted in rat femur bone marrow cavities, and then the pull-out force was measured. The pull-out force of micro-roughened PEEK was about four times higher than that of the mirror-polished PEEK. These results showed that micro-roughening of PEEK using the sandblast method was able to improve osseointegration, partly through elevating proliferation and differentiation of RMSCs.

DOI： 10.1080/09205063.2018.1461448

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To evaluate the acid resistance of various antibacterial ammonium hexafluorosilicate (SiF) solutions. Methods: Antibacterial SiF solutions were prepared with the addition of chlorhexidine (CHX), cetylpyridinium chloride (CPC), isopropyl methylphenol (IPMP), or epigallocatechin gallate (EGCG). Hydroxyapatite pellets were treated with SiF solution with or without antibacterial agents for 3 minutes. The demineralized depth of hydroxyapatite pellets after SiF treatment was measured using a surface roughness analyzer. Results: SiF+CPC solution showed equivalent acid resistance to SiF and AgF treatment. In contrast, the original acid resistance activity of SiF solution was diminished by the addition of other antibacterial agents (CHX, IPMP and EGCG). SiF with the addition of CPC was the most effective for reducing the demineralized depth, showing the same levels as those of SiF and AgF.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

β-Tricalcium phosphate [β-TCP] is the typical bone substitute due to its excellent osteoconductivity and bioresorbability. One of the keys to improve its potential as bone substitute is to introduce porous structure and its regulation. In this study, interconnected porous β-TCP blocks were fabricated through a setting reaction of β-TCP granules and subsequent heat treatment. First, β-TCP granules were mixed with HNO₃. Upon mixing, β-TCP granules were bridged with dicalcium phosphate dihydrate [DCPD: CaHPO₄·2H₂O] containing Ca(NO₃)₂. Then, the DCPD-bridged β-TCP was heated at 1100°C. During the heating process, DCPD containing Ca(NO₃)₂ transformed into β-TCP and bonded with β-TCP granules. As a result, an interconnected porous β-TCP block formed. The diametral tensile strength and porosity of the interconnected porous β-TCP block fabricated from 200–300-μm β-TCP granules and 5 N HNO₃ and then heated at 1,100°C were 1.4 ± 0.2 MPa and 57% ± 2%, respectively.

DOI： 10.1002/jbm.a.36285

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Octacalcium phosphate (OCP) foam with an interconnected porous structure was fabricated through phase conversion via a dissolution–precipitation reaction using calcium sulfate hemihydrate (CSH: CaSO₄·1/2H₂O) granules as precursors in a sodium dihydrogen phosphate (NaDP: NaH₂PO₄) solution. The diametral tensile strength and porosity of the OCP foam were 0.15 ± 0.04 MPa and 69.4% ± 0.04%, respectively. When the OCP foam was implanted into bone defects in a rabbit femur, the OCP foam showed an excellent tissue response, and the bone penetrated into the porous structure. The osteoconductivity and bone-replacement rate were significantly higher than those of an OCP compact.

DOI： 10.1016/j.matlet.2017.10.051

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bone defect reconstruction would be greatly improved if β-tricalcium phosphate (β-TCP) granules had the ability to self-set without sacrificing their osteoconductivity potential. This study aimed to identify a method to permit β-TCP self-setting whilst maintaining good osteoconductivity. When mixed with acidic calcium phosphate solution, β-TCP granules were found to readily set, forming a fully interconnected porous structure. On mixing, dicalcium phosphate dihydrate crystals formed on the surface of β-TCP granules, bridging the granules and resulting in the setting reaction. The setting time of the β-TCP granular cement (β-TCP GC) was approximately 1 min and its mechanical strength, in terms of diametral tensile strength, was approximately 0.8 MPa. The β-TCP GC and β-TCP granules both showed the same level of osteoconductivity within rat calvaria bone defects. At 2 and 4 weeks post-implantation, new bone formation was comparable between the two β-TCP based bone substitutes. We conclude that β-TCP GC has excellent potential for use as a cement in bone defect reconstruction.

DOI： 10.1002/jbm.b.33891

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Interconnected porous calcium-deficient hydroxyapatite (cdHAp) blocks may be an ideal biomaterial to repair bone defects because of their greater similarity to human bone than that of sintered hydroxyapatite (HAp) with respect to calcium content and crystallinity. In particular, the interconnected pores in cdHAp may provide pathways for cell migration and tissue ingrowth. In this study, the feasibility of fabricating interconnected porous cdHAp blocks through the setting reaction of alpha-tricalcium phosphate (αTCP) spherical granules was investigated. It was found that regulation of cdHAp formation was important to fabricate interconnected porous cdHAp blocks. That is, cdHAp needed to precipitate preferentially at the contacting areas between αTCP spherical granules. Exposure of αTCP spherical granules to steam under appropriate pressure was effective for this purpose. When αTCP spherical granules were immersed in water at 100 °C, the setting reaction resulted in dense cdHAp blocks because of the free crystal growth of cdHAp in water. Therefore, steam was used to localize the water at the contacting areas between αTCP spherical granules, which was driven by the surface tension of the water. Without an applied load, no setting reaction was observed when αTCP spherical granules were exposed to steam at 100 °C for 12 h. In contrast, under a load of 20 MPa, cdHAp precipitated to bridge spherical granules, providing an interconnected porous cdHAp block. The porosity and diametral tensile strength of this block were approximately 63% and 1.5 MPa, respectively.

DOI： 10.1016/j.ceramint.2017.05.162

記述言語：英語   掲載種別：研究論文（学術雑誌）  

β-Tricalcium phosphate (β-Ca₃(PO₄)₂, β-TCP) powders were synthesized using wet polymeric precipitation method for the first time to our best knowledge. The results of X-ray diffraction analysis showed the formation of almost single a Ca-deficient hydroxyapatite (CDHA) phase of a poor crystallinity already at room temperature. With continuously increasing the calcination temperature up to 800 °C the crystalline β-TCP was obtained as the main phase. It was demonstrated that infrared spectroscopy is very effective method to characterize the formation of β-Ca₃(PO₄)₂. The SEM results showed that β-Ca₃(PO₄)₂ solids were homogeneous having a small particle size distribution. The β-TCP powders consisted of spherical particles varying in size from 100 to 300 nm. Fabricated β-TCP specimens were placed to the bones of the rats and maintained for 1–2 months. The histological properties of these samples will be also investigated.

DOI： 10.1016/j.apt.2017.06.014

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Carbonate apatite (CO₃Ap) foam with an interconnected porous structure is highly attractive as a scaffold for bone replacement. In this study, arbitrarily shaped CO₃Ap foam was formed from α-tricalcium phosphate (α-TCP) foam granules via a two-step process involving treatment with acidic calcium phosphate solution followed by hydrothermal treatment with NaHCO₃. The treatment with acidic calcium phosphate solution, which is key to fabricating arbitrarily shaped CO₃Ap foam, enables dicalcium hydrogen phosphate dihydrate (DCPD) crystals to form on the α-TCP foam granules. The generated DCPD crystals cause the α-TCP granules to interlock with each other, inducing an α-TCP/DCPD foam. The interlocking structure containing DCPD crystals can survive hydrothermal treatment with NaHCO₃. The arbitrarily shaped CO₃Ap foam was fabricated from the α-TCP/DCPD foam via hydrothermal treatment at 200 °C for 24 h in the presence of a large amount of NaHCO₃.

DOI： 10.1007/s10856-017-5937-0

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hemodialysis, one of the earliest artificial kidney systems, removes uremic toxins via diffusion through a semipermeable porous membrane into the dialysate fluid. Miniaturization of the present hemodialysis system into a portable and wearable device to maintain continuous removal of uremic toxins would require that the amount of dialysate used within a closed-system is greatly reduced. Diffused uremic toxins within a closed-system dialysate need to be removed to maintain the optimum concentration gradient for continuous uremic toxin removal by the dialyzer. In this dialysate regenerative system, adsorption of uremic toxins by nanoporous biomaterials is essential. Throughout the years of artificial kidney development, activated carbon has been identified as a potential adsorbent for uremic toxins. Adsorption of uremic toxins necessitates nanoporous biomaterials, especially activated carbon. Nanoporous biomaterials are also utilized in hemoperfusion for uremic toxin removal. Further miniaturization of artificial kidney system and improvements on uremic toxin adsorption capacity would require high performance nanoporous biomaterials which possess not only higher surface area, controlled pore size, but also designed architecture or structure and surface functional groups. This article reviews on various nanoporous biomaterials used in current artificial kidney systems and several emerging nanoporous biomaterials.

DOI： 10.1002/jbm.b.33475

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Abstract: This study aimed to evaluate in vivo behavior of a carbonate apatite (CO₃Ap) block fabricated by compositional transformation via a dissolution–precipitation reaction using a calcium hydrogen phosphate dihydrate [DCPD: CaHPO₄·2H₂O] block as a precursor. These blocks were used to reconstruct defects in the femur and tibia of rabbits, using sintered dense hydroxyapatite (HAp) blocks as the control. Both the CO₃Ap and HAp blocks showed excellent tissue response and good osteoconductivity. HAp block maintained its structure even after 24 weeks of implantation, so no bone replacement of the implant was observed throughout the post-implantation period in either femoral or tibial bone defects. In contrast, CO₃Ap was resorbed with increasing time after implantation and replaced with new bone. The CO₃Ap block was resorbed approximately twice as fast at the metaphysis of the proximal tibia than at the epiphysis of the distal femur. The CO₃Ap block was resorbed at an approximately linear change over time, with complete resorption was estimated by extrapolation of data at approximately 1−1.5 years. Hence, the CO₃Ap block fabricated in this study has potential value as an ideal artificial bone substitute because of its resorption and subsequent replacement by bone.

DOI： 10.1007/s10856-017-5896-5

記述言語：英語   掲載種別：研究論文（学術雑誌）  

β-Tricalcium phosphate (β-TCP) has attracted much attention as an artificial bone substitute owing to its biocompatibility and osteoconductivity. In this study, osteoconductivity of β-TCP bone substitute was enhanced without using growth factors or cells. Dicalcium phosphate dihydrate (DCPD), which is known to possess the highest solubility among calcium phosphates, was coated on β-TCP granules by exposing their surface with acidic calcium phosphate solution. The amount of coated DCPD was regulated by changing the reaction time between β-TCP granules and acidic calcium phosphate solution. Histomorphometry analysis obtained from histological results revealed that the approximately 10 mol% DCPD-coated β-TCP granules showed the largest new bone formation compared to DCPD-free β-TCP granules, approximately 2.5 mol% DCPD-coated β-TCP granules, or approximately 27 mol% DCPD-coated β-TCP granules after 2 and 4 weeks of implantation. Based on this finding, we demonstrate that the osteoconductivity of β-TCP granules could be improved by coating their surface with an appropriate amount of DCPD.

DOI： 10.1016/j.msec.2017.03.004

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Calcium carbonate (CaCO₃) has been used as a bone substitute, and is a precursor for carbonate apatite, which is also a promising bone substitute. However, limited studies have been reported on the fabrication of artificial calcite blocks. In the present study, cylindrical calcite blocks (ϕ6 × 3 mm) were fabricated by compositional transformation based on dissolution–precipitation reactions using different calcium sulfate blocks as a precursor. In the dissolution–precipitation reactions, both CaSO₄·2H₂O and CaSO₄ transformed into calcite, a polymorph of CaCO₃, while maintaining their macroscopic structure when immersed in 1 mol/L Na₂CO₃ solution at 80 °C for 1 week. The diametral tensile strengths of the calcite blocks formed using CaSO₄·2H₂O and CaSO₄ were 1.0 ± 0.3 and 2.3 ± 0.7 MPa, respectively. The fabrication of calcite blocks using CaSO₄·2H₂O and CaSO₄ proposed in this investigation may be a useful method to produce calcite blocks because of the self-setting ability and high temperature stability of gypsum precursors.

DOI： 10.1016/j.msec.2016.11.093

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Carbonate apatite (CO₃Ap) block, which is a bone replacement used to repair defects, was fabricated through a dissolution-precipitation reaction using a calcium hydrogen phosphate dihydrate (DCPD) block as a precursor. When the DCPD block was immersed in NaHCO₃ or Na₂CO₃ solution at 80 °C, DCPD converted to CO₃Ap within 3 days. β-Tricalcium phosphate was formed as an intermediate phase, and it was completely converted to CO₃Ap within 2 weeks when the DCPD block was immersed in Na₂CO₃ solution. Although the crystal structures of the DCPD and CO₃Ap blocks were different, the macroscopic structure was maintained during the compositional transformation through the dissolution-precipitation reaction. CO₃Ap block fabricated in NaHCO₃ or Na₂CO₃ solution contained 12.9 and 15.8 wt % carbonate, respectively. The diametral tensile strength of the CO₃Ap block was 2 MPa, and the porosity was approximately 57% regardless of the carbonate solution. DCPD is a useful precursor for the fabrication of CO₃Ap block.

DOI： 10.3390/ma10040374

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We recently reported that when an acidic calcium phosphate solution is mixed with β-tricalcium phosphate (β-TCP) granules, the resulting dicalcium phosphate dihydrate (DCPD) crystals form bridges between the β-TCP granules, creating a set interconnected porous structure in approximately 1 min. Although this self-setting β-TCP granular cement (β-TCPGC) is useful for clinical applications, the short setting time is a key drawback for handling. In this study, the setting time of β-TCPGC was adjusted with the addition of citric acid, which is a known inhibiter of DCPD crystal growth. As the concentration of citric acid in the acidic calcium phosphate solution increased, the amount of DCPD formation in the set β-TCPGC decreased, and the crystal morphology of DCPD became elongated. β-TCPGC prepared with various citric acid concentrations were used as grafting material in rat calvarial bone defects to evaluate bone regeneration in vivo. Four weeks after implantation, no inflammatory reaction and approximately 20% new bone formation were observed, regardless of the presence or absence of citric acid in the liquid phase of β-TCPGC. We concluded, therefore, that citric acid might be a useful retarder of β-TCPGC setting times.

DOI： 10.1088/1748-605X/aa5aea

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Carbonate apatite (CO₃Ap) that contains 6-9 wt% carbonate in apatitic structure is the composition of human bone. Unfortunately, CO₃Ap cannot be sintered due to the presence of CO₃. CO₃Ap block was found to be fabricated based on a compositional transformation though dissolution-precipitation reaction using a precursor such as calcite block. CO₃Ap block thus fabricated up-regulate the differentiation of osteoblastic cells and resorbed by the osteoclasts. As results of these response to cells, CO₃Ap block demonstrate much better osteoconductivity than hydroxyapatite [HAp: Ca₁₀(PO₄)₆(OH)₂)] which is currently used artificial bone substitute. Also, CO₃Ap block was found to be replace to new bone similar to autograft even though HAp would not replace to bone. Clinical trial of CO₃Ap is now in progress, and CO₃Ap will be available for its clinical use next year.

DOI： 10.2465/gkk.161217

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The regulation of biofilm formation on dental materials such as denture bases is key to oral health. Recently, a biocompatible phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) coating, was reported to inhibit sucrose-dependent biofilm formation by Streptococcus mutans, a cariogenic bacterium, on the surface of poly(methyl methacrylate) (PMMA) denture bases. However, S. mutans is a minor component of the oral microbiome and does not play an important role in biofilm formation in the absence of sucrose. Other, more predominant oral streptococci must play an indispensable role in sucrose-independent biofilm formation. In the present study, the effect of PMB coating on PMMA was evaluated using various oral streptococci that are known to be initial colonizers during biofilm formation on tooth surfaces. PMB coating on PMMA drastically reduced sucrose-dependent tight biofilm formation by two cariogenic bacteria (S. mutans and Streptococcus sobrinus), among seven tested oral streptococci, as described previously [N. Takahashi, F. Iwasa, Y. Inoue, H. Morisaki, K. Ishihara, K. Baba, J. Prosthet. Dent. 112 (2014) 194–203]. Streptococci other than S. mutans and S. sobrinus did not exhibit tight biofilm formation even in the presence of sucrose. On the other hand, all seven species of oral streptococci exhibited distinctly reduced glucose-dependent soft biofilm retention on PMB-coated PMMA. We conclude that PMB coating on PMMA surfaces inhibits biofilm attachment by initial colonizer oral streptococci, even in the absence of sucrose, indicating that PMB coating may help maintain clean conditions on PMMA surfaces in the oral cavity.

DOI： 10.1016/j.apsusc.2016.08.108

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： org/10.1016/j.msec.2016.05.090

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2109/jcersj2.16046

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10856-016-5741-2

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1177/0885328215601939

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： org/10.1016/j.ceramint.2015.12.017

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jbm.a.35604

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ma9040283

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.msec.2015.10.024

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： org/10.1016/j.ceramint.2015.08.081

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4028/www.scientific.net/AMR.1133.50

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ceramint.2015.07.146

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/C5TB01679G

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10856-015-5570-8

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1155/2015/579541

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10856-015-5548-6

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.msec.2014.12.059

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10856-005-6987-2

DOI： 10.1016/j.biomaterials.2004.07.022

DOI： 10.1007/s10856-005-4753-0

DOI： 10.1002/jbm.b.20034

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1023/B:JMSM.0000010092.01661.a8

DOI： 10.2109/jcersj.112.434

DOI： 10.1002/jbm.b.10031

DOI： 10.1016/j.biomaterials.2003.08.003

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/S0142-9612(03)00151-0

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/S0142-9612(02)00079-0

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jbm.10332

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/S0928-4931(02)00108-X

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

開催年月日： 2022年9月

記述言語：英語  

開催地：Venice, Italy.(Oral 9.20)   国名：イタリア共和国  

開催年月日： 2022年5月

記述言語：日本語  

国名：日本国  

開催年月日： 2022年5月

記述言語：日本語  

国名：日本国  

開催年月日： 2022年5月

記述言語：日本語  

国名：日本国  

開催年月日： 2022年5月

記述言語：英語  

国名：日本国  

開催年月日： 2022年5月

記述言語：英語  

国名：日本国  

開催年月日： 2022年5月

記述言語：日本語  

国名：日本国  

開催年月日： 2022年5月

記述言語：日本語  

国名：日本国  

開催年月日： 2021年12月

記述言語：英語  

開催地：（Web開催）   国名：日本国