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Electronic toll collection (ETC), known as a non-stop toll collection system which can automatically realize payment by setting the identification antenna at the entrance, is always suffering from information exchange interruption caused by beam switching. A circularly polarized sector beam antenna array operating at 5.8 GHz with flat-top coverage is proposed, based on the weighted constrained method of the maximum power transmission efficiency (WCMMPTE). By setting the test receiving antennas at the specific angles of the ETC antenna array to be designed, constraints on the received power are introduced to control the radiation pattern and obtain the optimized distribution of excitations for antenna elements. A 1-to-16 feeding network, based on the microstrip transmission line theory is designed to feed a 4 × 4 antenna array. Simulation results show that the half-power beamwidth covers an angular range of -30° to 30° while the axial ratio is below 3dB, which meets the ETC requirements. Furthermore, the gain fluctuation among the needed range of -30° to 30° is lower than 0.7 dB, which is suitable for the ETC system to achieve a stable signal strength and uninterrupted communication.
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Tunnel communication always suffers from path loss and multipath effects caused by surrounding walls. Meanwhile, the traditional leaky coaxial cables are expensive to deploy, inconvenient to operate, and difficult to maintain, leading to many problems in practical use. To solve the abovementioned problems, a low-profile printed dipole array operating at 3.5 GHz with bidirectional endfire radiation is designed based on the method of maximum power transmission efficiency (MMPTE). By setting two virtual test receiving dipoles at the two opposite endfire directions and then maximizing the power transmission efficiency between the printed dipole array to be designed and the test receiving antennas, the optimal amplitudes and phases for the array elements are obtained. Based on the optimal distributions of excitations, the simulation results show that the proposed eight-element printed dipole array can simultaneously generate two mirrored endfire beams towards opposite directions. Furthermore, the corresponding normalized cross-polarization levels are lower than -22.3 dBi both in the azimuth and elevation planes. The peak endfire gain is 10.7 dBi with maintenance of higher than 10 dBi from 3.23 GHz to 3.66 GHz, which is suitable for tunnel communication.
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The 3D printing technology with unique strategies for accurate fabrication of biomaterials in regenerative medicine has been widely applied in bone regeneration. However, the traditional 3D printing scaffolds are only stacked by solid struts without any hollow channel structures, which limits the new bone tissue formation. In this study, a special 3D scaffold with hollow channels and a micro-nano surface was prepared by a modified 3D printing strategy combined with the hydrothermal treatment approach. By regulating the reaction solution of hydrothermal treatment, the micro-nano structures formed on the surface of scaffolds can be successfully controlled. Moreover, the scaffolds have the ability to facilitate the attachment and proliferation of BMSCs after culturing for 1, 3, and 7 days in vitro. Interestingly, the in vivo results demonstrated that the hollow channels and the micro-nano surface present synergistic effects on bone regeneration. They both boost the new bone formation in femur defects in rabbits for 12 weeks after operation. The study demonstrates a 3D scaffold with special surface microstructures and hollow struts that can overcome the shortages of most traditional scaffolds and meanwhile improve the bioactivity of biomaterials for bone tissue engineering.
Asunto(s)
Regeneración Ósea , Andamios del Tejido , Animales , Materiales Biocompatibles/farmacología , Impresión Tridimensional , Conejos , Ingeniería de TejidosRESUMEN
Bacterial infection poses a significant risk with the wide application of bone graft materials. Designing bone grafts with good antibacterial performance and excellent bone-forming activity is of particular significance for bone tissue engineering. In our study, a 3D printing method was used to prepare ß-tricalcium phosphate (ß-TCP) bioceramic scaffolds. Silver (Ag) nanoparticles were uniformly dispersed on graphene oxide (GO) to form a homogeneous nanocomposite (named Ag@GO) with different Ag-to-graphene oxide mass ratios, with this being synthesized via the liquid chemical reduction approach. Ag@GO nanocomposites were successfully modified on the ß-TCP scaffolds by a simple soaking method to achieve bifunctional biomaterials with antibacterial and osteogenic activity. The prepared scaffolds possessed a connected network with triangle pore morphology and the surfaces of the ß-TCP scaffolds were uniformly modified by the Ag@GO nanocomposite layers. The Ag content in the scaffolds was controlled by changing the coating times and concentration of the Ag@GO nanocomposites. The antibacterial activity of the scaffolds was assessed with Gram-negative bacteria (Escherichia coli, E. coli). The results demonstrated that the scaffolds with Ag@GO nanocomposites presented excellent antibacterial activity. In addition, the scaffolds coated with Ag@GO nanocomposites conspicuously accelerated the osteogenic differentiation of rabbit bone marrow stromal cells by improving their alkaline phosphatase activity and bone-related gene expression (osteopontin, runt-related transcription factor 2, osteocalcin and bone sialoprotein). This study demonstrates that bifunctional scaffolds with a combination of antibacterial and osteogenic activity can be achieved for the reconstruction of large-bone defects while preventing or treating infections.
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Bioimpresión/métodos , Huesos/citología , Fosfatos de Calcio/química , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Antibacterianos/química , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Nanocompuestos/química , OsteogénesisRESUMEN
Bioactive materials with osteostimulation properties have the potential to promote bone regeneration. We have found that silicate-based biomaterials have the osteostimulation ability for regeneration of large bone defects; however, the corresponding mechanism is unclear. In this study, we set out to elucidate the potential mechanism of silicate-based biomaterials with osteostimulation ability. A model silicate bioceramic, nagelschmidtite (NAGEL, Ca7P2Si2O16), was applied to study their ionic products on the effect of the Bone morphogenic protein (BMP) signaling pathway for osteoblast MC3T3-E1 as NAGEL has been previously shown to have excellent in vitro and in vivo bone-forming activity. BMP signaling, especially BMP2, is involved in bone formation during mammalian development and exhibits versatile regulatory functions in the body. It is found that NAGEL bioceramics significantly enhance the migration and osteoblastic differentiation of MC3T3-E1. mRNA and protein expression of BMP2 is enhanced by NAGEL bioceramics in a dose-dependent manner. Moreover, NAGEL bioceramics activate the Smad-dependent BMP signaling pathway and induce the activation of the BMP downstream cascade (OCN, OPN and Runx2). The accumulation of phosphorylated-Smad1/5 is induced by NAGEL bioceramics in the MC3T3-E1 cell nucleus. It is further found that NAGEL bioceramic-mediated migration, osteoblastic differentiation and the activation of the BMP downstream cascade are significantly downregulated by inhibition of BMP2 activity. Our results suggest that silicate-based NAGEL bioceramics possess excellent in vitro osteostimulation properties and the possible mechanism of silicate-based biomaterials with distinct osteostimulation may be directly related to the activation of the BMP2 signaling pathway of osteoblasts by release of Si-containing bioactive ionic products.
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The hierarchical structure of biomaterials plays an important role in the process of tissue reconstruction and regeneration. 3D-plotted scaffolds have been widely used for bone tissue engineering due to their controlled macropore structure and mechanical properties. However, the lack of micro- or nano-structures on the strut surface of 3D-plotted scaffolds, especially for bioceramic scaffolds, limits their biological activity. Inspired by the adhesive versatility of mussels and the active ion-chelating capacity of polydopamine, we set out to prepare a hierarchical bioceramic scaffold with controlled macropores and mussel-inspired surface nanolayers by combining the 3D-plotting technique with the polydopamine/apatite hybrid strategy in order to synergistically accelerate the osteogenesis and angiogenesis. ß-Tricalcium phosphate (TCP) scaffolds were firstly 3D-plotted and then treated in dopamine-Tris/HCl and dopamine-SBF solutions to obtain TCP-DOPA-Tris and TCP-DOPA-SBF scaffolds, respectively. It was found that polydopamine/apatite hybrid nanolayers were formed on the surface of both TCP-DOPA-Tris and TCP-DOPA-SBF scaffolds and TCP-DOPA-SBF scaffolds induced apatite mineralization for the second time during the cell culture. As compared to TCP scaffolds, both TCP-DOPA-Tris and TCP-DOPA-SBF scaffolds significantly promoted the osteogenesis of bone marrow stromal cells (BMSCs) as well as the angiogenesis of human umbilical vein endothelial cells (HUVECs), and the TCP-DOPA-SBF group presented the highest in vitro osteogenic/angiogenic activity among the three groups. Furthermore, both TCP-DOPA-Tris and TCP-DOPA-SBF scaffolds significantly improved the formation of new bone in vivo as compared to TCP scaffolds without a nanostructured surface. Our results suggest that the utilization of a mussel-inspired Ca, P-chelated polydopamine nanolayer on 3D-plotted bioceramic scaffolds is a viable and effective strategy to construct a hierarchical structure for synergistically accelerating osteogenesis.
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Materiales Biocompatibles , Nanoestructuras , Osteogénesis , Andamios del Tejido , Animales , Bivalvos , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Células del Estroma/citología , Ingeniería de TejidosRESUMEN
A new approach has been developed to fabricate tough hybrid hydrogels by employing dual enzyme-mediated redox initiation to achieve post-self-assembly cross-linking polymerization. The resulting hydrogel combines the merits of supramolecular hydrogels with polymeric hydrogels to achieve higher mechanical strength and porous networks. Designed 3D constructs were fabricated via in situ 3D printing. The in situ immobilized GOx/HRP in Gel II exhibited superactivity compared to free enzymes, which might be attributed to the synergistic effect of co-localized GOx and HRP minimizing the distances for mass transport between the gel and the bulk solution. This mechanically strong hybrid hydrogel maintained high reusability and thermal stability as well. In addition, in situ 3D cell culture was demonstrated, thus indicating that this biodegradable hybrid hydrogel is biocompatible with cells. The subsequent 3D cell printing further indicates that the hybrid hydrogel is a promising scaffold for bio-related applications such as biocatalysis and tissue engineering.
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Simultaneous therapy and regeneration of bone tumor-induced defects still remain to be a significant challenge. Conventional therapy strategy by implanting bone graft materials can regenerate the bone defects after surgery but cannot kill residual tumor cells. In this study, we successfully prepared a 3D-printed ß-tricalcium phosphate bioceramic scaffold with surface modification of Fe3O4 nanoparticles/graphene oxide nanocomposite layers (named ß-TCP-Fe-GO). The prepared ß-TCP-Fe-GO scaffolds possess a highly ordered macroporous structure with triangle pore morphology and a pore size of around 300-500 µm. The struts of ß-TCP-Fe-GO scaffolds were uniformly deposited with Fe3O4/GO sandwich-like composite layers in which nano-sized Fe3O4 particles were wrapped by GO sheets. The Fe3O4 content in the ß-TCP-Fe-GO scaffolds can be effectively modulated by controlling the coating times; the final content of Fe3O4 in ß-TCP-8Fe-GO scaffolds is no more than 1% after coating 8 times. Such low content of Fe3O4 in the scaffolds endows them with super paramagnetic behavior and hyperthermal effects. The temperature of the scaffolds can be modulated in the range 50-80 °C under an alternating magnetic field for 15 minutes by controlling the magnetic intensity and Fe3O4 content. The excellent hyperthermal effect of ß-TCP-Fe-GO scaffolds induced more than 75% cell death for osteosarcoma cells (MG-63) in vitro. Furthermore, the ß-TCP-Fe-GO scaffolds significantly enhanced alkaline phosphatase (ALP) activity and osteogenic gene expression, such as OPN, Runx2, OCN and BSP, of rabbit bone marrow stromal cells (rBMSCs) and significantly stimulated rBMSCs proliferation as compared to pure ß-TCP scaffolds by the synergistic effect of GO and the released Fe ions. Therefore, the prepared ß-TCP-Fe-GO scaffolds possess prominent magnetothermal ability and excellent bone-forming activity. This study is believed to pave the way for the design and fabrication of novel tissue engineering scaffolds in a combination of therapy and regeneration functions.
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The development of an artificial graft with distinct osteogenetic activity to enhance osseointegration and to induce the formation of biomimetic tissue structure for ligament reconstruction remains a significant challenge. Inspired by mussels, biomimetic calcium phosphate apatite/polydopamine hybridized-polyethylene terephthalate (APA/PDA-PET) grafts were successfully prepared. The efficacy and mechanism of APA/PDA-PET grafts to induce osseointegration were systematically investigated. The results from the in vitro study indicated that the prepared APA/PDA-PET grafts support the attachment of bone marrow stromal cells (BMSCs) and stimulate the proliferation and osteogenic/angiogenic differentiation of BMSCs via activation of the PKC/p-ERK1/2 signaling pathway. In vivo, histological and radiological results further demonstrate that the APA/PDA-PET grafts significantly improve osseointegration by inducing the formation of new bone tissue and the fibrocartilage transitional zone compared with pure PET grafts. In addition, the pull-out strength of the APA/PDA-PET grafts is significantly higher than that of the pure PET grafts 12 weeks after surgery. These results suggest that this mussel-inspired biomimetic method is an effective strategy for modifying artificial grafts, and the prepared APA/PDA-PET grafts, which possess a beneficial interface, can significantly improve in vivo osseointegration for ligament reconstruction via the synergistic effect of polydopamine and apatite.
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Materiales Biomiméticos/síntesis química , Bioprótesis , Bivalvos/química , Regeneración Tisular Dirigida/instrumentación , Ligamentos/lesiones , Ligamentos/cirugía , Animales , Fosfatos de Calcio/química , Diferenciación Celular/fisiología , Proliferación Celular , Supervivencia Celular/fisiología , Células Cultivadas , Diseño de Equipo , Análisis de Falla de Equipo , Ensayo de Materiales , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Osteogénesis/fisiología , Conejos , Procedimientos de Cirugía Plástica/instrumentación , Trasplantes/trasplanteRESUMEN
Bioactive three-dimensional (3D) scaffolds play a key role in the repair or regeneration of large bone defects. There are many methods to prepare 3D scaffolds, among which the 3D-plotting technique is a promising strategy as the scaffolds prepared by this method possess not only improved mechanical properties and interconnectivity, but also ordered large-pore structure. However, the low cell attachment rate in the interior of the 3D-plotted scaffolds, especially for 3D-plotted bioceramic scaffolds, inhibits the osteogenesis of stem cells in the scaffolds both in vitro and in vivo. The aim of this study is to prepare hierarchically porous composite scaffolds in order to improve the cell attachment, and further stimulate the in vitro and in vivo osteogenesis. We successfully fabricated hierarchically porous bioceramic-silk (BC-silk) composite scaffolds by a combination of the 3D-plotting technique with the freeze-drying method, and further investigated the attachment, proliferation and osteogenic differentiation of bone marrow stromal cells (BMSCs) in the scaffolds as well as the in vivo osteogenesis of the prepared porous scaffolds. The results showed that the hierarchical structure in the composite scaffolds was composed of first-level pores (â¼1 mm) of the bioceramic scaffold and second-level pores (â¼50-100 µm) of the silk matrix. The prepared BC-silk composite scaffolds possessed excellent apatite-mineralization ability and mechanical properties with compressive strength up to 25 MPa. In addition, hierarchically porous BC-silk scaffolds presented significantly enhanced attachment rate of BMSCs, around 4 times that of pure BC scaffolds without hierarchical pore structures. BC-silk scaffolds with hierarchical pore structures showed distinctively improved cell proliferation, ALP activity and bone-related gene expression as compared to BC scaffolds without hierarchical pore structure. Furthermore, hierarchically porous BC-silk scaffolds significantly enhanced the formation of new bone in vivo as compared to BC scaffolds. Our results suggest that the combination of 3D-plotting with the freeze-drying method is a viable strategy to construct hierarchical pore structures in 3D-plotted scaffolds, and the hierarchical pore structure plays an important role in improving the in vitro and in vivo osteogenesis of 3D-plotted bioceramic scaffolds for bone regeneration application.
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It is known that porous scaffolds play an important role in bone/periodontal tissue engineering. A new nagelschmidtite (NAGEL, Ca7Si2P2O16) ceramic has recently been prepared which shows excellent apatite mineralization ability and osteo-/cementostimulation properties in vitro. However, up to now porous NAGEL scaffolds have not been developed yet. There has been no systematic study of the effect of macropore morphology of bioceramic scaffolds on their physico-chemical and biological properties. The aim of this study was to prepare NAGEL scaffolds for bone tissue engineering applications. We applied a modified three-dimensional (3-D) plotting method to prepare highly controllable NAGEL scaffolds and investigated the effect of macropore morphology on the physico-chemical and biological properties. The results showed that the macropore size and morphology of 3-D plotted NAGEL scaffolds could be effectively controlled. Compared with ß-tricalcium phosphate (ß-TCP) scaffolds NAGEL scaffolds possess a significantly enhanced compressive strength, a higher modulus and better degradability. Nagel scaffolds with a square pore morphology presented a higher compressive strength, a higher modulus and greater weight loss rate than those with triangular and parallelogram pore morphologies. In addition, all of the NAGEL scaffolds with the three macropore morphologies supported the attachment and proliferation of MC3T3 cells. The proliferation of MC3T3 cells on NAGEL scaffolds with triangular and parallelogram structures was higher than that on ß-TCP scaffolds with the same pore structure. Cells on all three groups of NAGEL scaffolds revealed higher alkaline phosphatase (ALP) activity compared with cells on ß-TCP scaffolds, and among the three NAGEL scaffolds groups those with a parallelogram pore structure showed the highest ALP activity. Furthermore, the angiogenic cell experiments showed that the ionic products from NAGEL scaffolds promoted tube formation, expression of pro-angiogenic factors and their receptors on human umbilical vein endothelial (HUVECs) compared with ß-TCP scaffolds, indicating that NAGEL scaffolds possessed improved angiogenesis capacity. Our results suggest that 3-D plotted NAGEL scaffolds are a promising bioactive material for bone tissue engineering by virtue of their highly controllable macropore structure, excellent mechanical strength, degradability and in vitro biological response to osteogenic/angiogenic cells.
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Materiales Biocompatibles/farmacología , Fosfatos de Calcio/farmacología , Cerámica/farmacología , Ensayo de Materiales , Andamios del Tejido/química , Fosfatasa Alcalina/metabolismo , Animales , Adhesión Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Fuerza Compresiva/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Iones , Ratones , Peso Molecular , Neovascularización Fisiológica/efectos de los fármacos , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/enzimología , Osteoblastos/ultraestructura , Tamaño de la Partícula , Porosidad , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Difracción de Rayos XRESUMEN
The nanostructured surface of biomaterials plays an important role in improving their in vitro cellular bioactivity as well as stimulating in vivo tissue regeneration. Inspired by the mussel's adhesive versatility, which is thought to be due to the plaque-substrate interface being rich in 3,4-dihydroxy-l-phenylalamine (DOPA) and lysine amino acids, in this study we developed a self-assembly method to prepare a uniform calcium phosphate (Ca-P)/polydopamine composite nanolayer on the surface of ß-tricalcium phosphate (ß-TCP) bioceramics by soaking ß-TCP bioceramics in Tris-dopamine solution. It was found that the addition of dopamine, reaction temperature and reaction time are three key factors inducing the formation of a uniform Ca-P/polydopamine composite nanolayer. The formation mechanism of a Ca-P/polydopamine composite nanolayer involved two important steps: (i) the addition of dopamine to Tris-HCl solution decreases the pH value and accelerates Ca and P ionic dissolution from the crystal boundaries of ß-TCP ceramics; (ii) dopamine is polymerized to form self-assembled polydopamine film and, at the same time, nanosized Ca-P particles are mineralized with the assistance of polydopamine, in which the formation of polydopamine occurs simultaneously with Ca-P mineralization (formation of nanosized microparticles composed of calcium phosphate-based materials), and finally a self-assembled Ca-P/polydopamine composite nanolayer forms on the surface of the ß-TCP ceramics. Furthermore, the formed self-assembled Ca-P/polydopamine composite nanolayer significantly enhances the surface roughness and hydrophilicity of ß-TCP ceramics, and stimulates the attachment, proliferation, alkaline phosphate (ALP) activity and bone-related gene expression (ALP, OCN, COL1 and Runx2) of human bone marrow stromal cells. Our results suggest that the preparation of self-assembled Ca-P/polydopamine composite nanolayers is a viable method to modify the surface of biomaterials by significantly improving their surface physicochemical properties and cellular bioactivity for bone regeneration application.
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Materiales Biocompatibles/farmacología , Bivalvos/química , Células de la Médula Ósea/citología , Cerámica/farmacología , Indoles/farmacología , Nanopartículas/química , Osteogénesis/efectos de los fármacos , Polímeros/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/ultraestructura , Fosfatos de Calcio/farmacología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Proliferación Celular/efectos de los fármacos , Cerámica/síntesis química , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno/efectos de los fármacos , Interacciones Hidrofóbicas e Hidrofílicas/efectos de los fármacos , Microscopía de Fuerza Atómica , Nanopartículas/ultraestructura , Osteogénesis/genética , Células del Estroma/citología , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Células del Estroma/ultraestructura , Propiedades de Superficie , Temperatura , Factores de Tiempo , Agua/químicaRESUMEN
It is accepted that the accelerated differentiation of tissue cells on bioactive materials is of great importance to regenerate the lost tissues. It was previously reported that lithium (Li) ions could enhance the in vitro proliferation and differentiation of retinoblastoma cells and endometrium epithelia by activating the Wnt canonical signalling pathway. It is interesting to incorporate Li ions into bioactive ceramics, such as ß-tricalcium phosphate (Li-ß-TCP), in order to stimulate both osteogenic and cementogenic differentiation of different stem cells for the regeneration of bone/periodontal tissues. Therefore, the aim of this study was to investigate the interactions of human periodontal ligament cells (hPDLCs) and human bone marrow stromal cells (hBMSCs) with Li-ß-TCP bioceramic bulks and their ionic extracts, and further explore the osteogenic and cementogenic stimulation of Li-ß-TCP bioceramics and the possible molecular mechanisms. The results showed that Li-ß-TCP bioceramic disks supported the cell attachment and proliferation, and significantly enhanced bone/cementum-related gene expression, Wnt canonical signalling pathway activation for both hPDLCs and hBMSCs, compared to conventional ß-TCP bioceramic disks without Li. The release of Li from Li-ß-TCP powders could significantly promote the bone/cementum-related gene expression for both hPDLCs and hBMSCs compared to pure ß-TCP extracts without Li release. Our results suggest that the combination of Li with ß-TCP bioceramics may be a promising method to enhance bone/cementum regeneration as Li-ß-TCP possesses excellent in vitro osteogenic and cementogenic stimulation properties by inducing bone/cementum-related gene expression in both hPDLCs and hBMSCs.
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Bioactive materials with osteostimulation properties are of great importance to promote osteogenic differentiation of human bone marrow stromal cells (hBMSCs) for potential bone regeneration. We have recently synthesized nagelschmidtite (NAGEL, Ca7Si2P2O16) ceramic powders which showed excellent apatite-mineralization ability. The aim of this study was to investigate the interaction of hBMSCs with NAGEL bioceramic bulks and their ionic extracts, and to explore the osteostimulation properties of NAGEL bioceramics and the possible molecular mechanism. The cell attachment, proliferation, bone-related gene expression (ALP, OPN and OCN) and WNT signalling pathways (WNT3a, FZD6, AXIN2 and CTNNB) of hBMSCs cultured on NAGEL bioceramic disks were systematically studied. We further investigated the biological effects of ionic products from NAGEL powders on cell proliferation and osteogenic differentiation of hBMSCs by culturing cells with NAGEL extracts. Furthermore, the effect of NAGEL bioceramics on the osteogenic differentiation in hBMSCs was also investigated with the addition of cardamonin, a WNT inhibitor. The results showed that NAGEL bioceramic disks supported the attachment and proliferation of hBMSCs, and significantly enhanced the bone-related gene expression and WNT signalling pathway of hBMSCs, compared to conventional beta-tricalcium phosphate (ß-TCP) bioceramic disks and blank controls. The ionic products from NAGEL powders also significantly promoted the proliferation, bone and WNT-related gene expression of hBMSCs. It was also identified that NAGEL bioceramics could bypass the action of the WNT inhibitor (10 µM) to stimulate the selected osteogenic genes in hBMSCs. Our results suggest that NAGEL bioceramics possess excellent in vitro osteostimulation properties. The possible mechanism for the osteostimulation may be directly related to the released Si, Ca and P-containing ionic products from NAGEL bioceramics which activate bone-related gene expression and WNT signalling pathway of hBMSCs. The present study suggests that NAGEL bioceramics are a potential bone regeneration material with significant osteostimulation capacity.
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Mussels possess the ability to attach to virtually any type of inorganic and organic surfaces due to the existence of phenylalamine and lysine amino acids. Inspired by the property of mussels, polydopamine has been used for modifying bioinert materials, such as metals, semiconductors and plastics to improve their surface hydrophilicity. However, there are no reports about the effect of a polydopamine modification on apatite mineralization and the biological response of bioactive ceramics (not bioinert materials) for bone regeneration applications. Akermanite bioceramics (AKT, Ca2MgSi2O7) are a typical bioactive material with osteostimulation properties for bone tissue regeneration. The aim of this study is to systematically investigate the effect of a polydopamine modification on the physicochemical and biological properties of AKT bioceramics, including attachment, proliferation, ALP activity and bone-related gene expression of tissue cells. The results show that a self-assembled polydopamine layer on the surface of AKT bioceramics was formed by incubating AKT bioceramics in a dopamine/Tris-HCl solution. Polydopamine-modified AKT (PDB-AKT) bioceramics showed significantly improved surface roughness, hydrophilicity and apatite-mineralization ability compared to AKT bioceramics. In addition, the polydopamine modification distinctively enhanced the attachment, proliferation, alkaline phosphate activity and bone-related gene expression of MC3T3 cells on AKT bioceramics. The possible reason for the improved cytocompatibility may be related to the improved surface roughness and apatite mineralization as well as the ionic environment at an early stage of cell culture. Our results suggest that the polydopamine modification is a viable method to further improve the apatite mineralization and biological response of bioactive ceramics for better bone regeneration applications, indicating that the polydopamine modification is a universal method to enhance the bioactivity for both bioinert and bioactive materials.
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It is of great importance to develop multifunctional bioactive scaffolds, which combine angiogenesis capacity, osteostimulation, and antibacterial properties for regenerating lost bone tissues. In order to achieve this aim, we prepared copper (Cu)-containing mesoporous bioactive glass (Cu-MBG) scaffolds with interconnective large pores (several hundred micrometer) and well-ordered mesopore channels (around 5 nm). Both Cu-MBG scaffolds and their ionic extracts could stimulate hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression in human bone marrow stromal cells (hBMSCs). In addition, both Cu-MBG scaffolds and their ionic extracts significantly promoted the osteogenic differentiation of hBMSCs by improving their bone-related gene expression (alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN)). Furthermore, Cu-MBG scaffolds could maintain a sustained release of ibuprofen and significantly inhibited the viability of bacteria. This study indicates that the incorporation of Cu(2+) ions into MBG scaffolds significantly enhances hypoxia-like tissue reaction leading to the coupling of angiogenesis and osteogenesis. Cu(2+) ions play an important role to offer the multifunctional properties of MBG scaffold system. This study has demonstrated that it is possible to develop multifunctional scaffolds by combining enhanced angiogenesis potential, osteostimulation, and antibacterial properties for the treatment of large bone defects.