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：Springer Science and Business Media LLC  

DOI： 10.1007/s10856-024-06833-8

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その他リンク： https://link.springer.com/article/10.1007/s10856-024-06833-8/fulltext.html

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：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   出版者・発行元：Frontiers in Bioengineering and Biotechnology  

Both the composition and architecture of artificial bone govern bone regeneration. Herein, carbonate apatite (CAp), which has a similar mineral composition to bone, was prepared by immersing calcium carbonate (CaCO3) in a phosphate solution with varying acidification levels (pH 6.0) to pH 8.9, to reveal the influence of pH on the composition and architecture of the resultant CAp granules. The composition, crystal morphology, and architecture of resultant CAp granules was well-characterized by X-ray diffraction, scanning electron microscopy, mercury intrusion porosimetry and so on. Consequently, the rate of compositional transformation from CaCO3 to CAp was much higher at pH 6.0 and pH 7.0 than pH 8.0 and pH 8.9. The pH of the phosphate solution did not affect the macroarchitecture of the resultant CAp granules. In contrast, the composition, crystal morphology, microarchitecture, and degradation behavior of the resultant CAp granules were affected by pH of the phosphate solution. In particular, the open-pore distributions and volumes of the CAp granules prepared at pH 6.0–8.9 were changed to reflect the microarchitecture of the samples. Therefore, this study revealed that the pH-controlled elution precipitation reaction is useful for controlling the composition, crystal morphology, microarchitecture, and degradation behavior of the resultant CAp, while preserving its macroarchitecture. Our findings provide fundamental insights into the design of artificial bones for bone regeneration.

DOI： 10.3389/fbioe.2024.1396275

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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：Elsevier BV  

DOI： 10.1016/j.ceramint.2024.04.341

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掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

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   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/14686996.2024.2303327

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   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Applied Bio Materials  

Ti surfaces must exhibit antibacterial activity without cytotoxicity to promote bone reconstruction and prevent infection simultaneously. In this study, we employed a two-step electrochemical treatment process, namely, microarc oxidation (MAO) and cathodic electrochemical deposition (CED), to modify Ti surfaces. During the MAO step, a porous TiO2 (pTiO2) layer with a surface roughness of approximately 2.0 μm was generated on the Ti surface, and in the CED step, Cu was deposited onto the pTiO2 layer on the Ti surface, forming Cu@pTiO2. Cu@pTiO2 exhibited a similar structure, adhesion strength, and crystal phase to pTiO2. Moreover, X-ray photoelectron spectroscopy (XPS) confirmed the presence of Cu in Cu@pTiO2 at an approximate concentration of 1.0 atom %. Cu@pTiO2 demonstrated a sustained release of Cu ions for a minimum of 28 days in a simulated in vivo environment. In vitro experiments revealed that Cu@pTiO2 effectively eradicated approximately 99% of Staphylococcus aureus and Escherichia coli and inhibited biofilm formation, in contrast to the Ti and pTiO2 surfaces. Moreover, Cu@pTiO2 supported the proliferation of osteoblast-like cells at a rate comparable to that observed on the Ti and pTiO2 surfaces. Similar to pTiO2, Cu@pTiO2 promoted the calcification of osteoblast-like cells compared with Ti. In summary, we successfully conferred antibacterial and pro-osteogenic activities to Ti surfaces without inducing cytotoxic effects or structural and mechanical alterations in pTiO2 through the application of MAO and CED processes. Moreover, we found that the pTiO2 layer promoted bacterial growth and biofilm formation more effectively than the Ti surface, highlighting the potential drawbacks of rough and porous surfaces. Our findings provide fundamental insights into the surface design of Ti-based medical devices for bone reconstruction and infection prevention.

DOI： 10.1021/acsabm.3c00860

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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   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：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/acsmaterialsau.3c00008

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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：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）  

DOI： https://doi.org/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：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）  

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：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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

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   掲載種別：研究論文（学術雑誌）  

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

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：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.

DOI： 10.1016/j.mtbio.2022.100247

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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：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：その他   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）  

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）  

DOI： 10.1016/j.ceramint.2021.09.188

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 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：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   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/nano.202000283

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/nano.202000283

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ijms22031373

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ijms22031373

その他リンク： https://www.mdpi.com/1422-0067/22/3/1373

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/acsabm.0c00060

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：その他   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： 10.1002/adbi.201900140

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.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The surface stability and compositions of catalysts under varied conditions play an important role in its activity and selectivity toward various reactions. In this paper, density functional theory based first principles calculations were used to investigate the stability and compositions of the first two layers of Pt-Pd alloys on Pd substrate under the electrode-potential dependent oxygen reduction conditions. The adsorption of O and OH have different preference surface compositions of Pt : Pd approximate to 50:50 and Pt : Pd approximate to 0 : 100, respectively. However, at high electrode potential, it is found that O should be dominant adsorbate on the surface. Therefore, the surface composition should favor the Pt : Pd approximate to 50 : 50. Moreover, this oxygen covered surface is characterized by weakened surface Pt-Pt bonds, which is attributed to the increase in the population of the Pt-Pt antibonding state. These findings support the experimentally observed Pd segregation from the as-prepared Pt/Pd(111) to the composition of Pt : Pd = 60 : 40 during ORR.

DOI： 10.7566/JPSJ.88.044802

その他リンク： https://journals.jps.jp/doi/full/10.7566/JPSJ.88.044802

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.7566/JPSJ.88.044802

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.7566/JPSJ.87.084802

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.7566/JPSJ.87.084802

その他リンク： https://doi.org/10.7566/JPSJ.87.084802

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/qua.25445

記述言語：英語   掲載種別：研究論文（学術雑誌）  

o-Quinone amines, which are relevant to various biological processes, can undergo spontaneous intramolecular cyclization (ring closure reaction by amino-terminated hydrocarbon side chain) that deactivates them toward another possible reactions, that is, thiol binding. Density functional theory-based calculation is employed for obtaining the potential energy curves along the C-N bond formation in the intramolecular cyclization of various o-quinone amines, viz., dopaminequinone, dopaquinone, N-methyl-dopaminequinone, N-formyl-dopaminequinone, and the corresponding methylene-inserted analogues. The activation barrier is decreased by introduction of alpha-carboxylate and N-methyl group whereas increased by introduction of N-formyl group. A negative correlation between the activation barriers and the level of highest occupied molecular orbital is pointed out. Furthermore, the methylene-inserted analogues show decreased activation barriers. This is explained by reduction of steric repulsion in the transition state.

DOI： 10.1002/qua.25445

その他リンク： https://onlinelibrary.wiley.com/doi/full/10.1002/qua.25445

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11664-017-5402-3

その他リンク： https://link.springer.com/article/10.1007/s11664-017-5402-3

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11664-017-5402-3

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11664-017-5299-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.7566/JPSJ.86.024804

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Using density functional theory-based first principles calculations, we investigated the changes in the energetics and electronic structures of rhododendrol (RD)-quinone for the initial step of two important reactions, viz., cyclization and thiol binding, to give significant insights into the mechanism of the cause of cytotoxic effects. We found that RD-quinone in the electroneutral structure cannot undergo cyclization, indicating a slow cyclization of RD-quinone at neutral pH. Furthermore, using methane thiolate ion as a model thiol, we found that the oxidized form of the cyclized RD-quinone, namely RD-cyclic quinone, exhibited a reduced binding energy for thiols. However, this reduction of binding energy is clearly smaller than the case of dopaquinone, which is a molecule originally involved in the melanin synthesis. This study clearly shows that RD-quinone has a preference toward thiol bindings than cyclization compared to the case of dopaquinone. Considering that thiol bindings have been reported to induce cytotoxic effects in various ways, the preference toward thiol bindings is an important chemical property for the cytotoxicity caused by RD.

DOI： 10.7566/JPSJ.86.024804

その他リンク： https://doi.org/10.7566/JPSJ.86.024804

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11664-017-5299-x

その他リンク： https://link.springer.com/article/10.1007/s11664-017-5299-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbagen.2014.10.024

その他リンク： http://dx.doi.org/10.1016/j.bbagen.2014.10.024

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbagen.2014.10.024

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/pcmr.12256

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/pcmr.12256

その他リンク： https://onlinelibrary.wiley.com/doi/full/10.1111/pcmr.12256

開催年月日： 2024年1月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：九州大学馬出キャンパス 九州大学医学部百年講堂   国名：日本国  

開催年月日： 2023年10月

記述言語：英語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2019年4月

記述言語：英語   会議種別：口頭発表（一般）  

国名：アメリカ合衆国  

開催年月日： 2018年11月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：九州大学西新プラザ　2階大会議室   国名：日本国  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語