Graphene-based hemostatic sponge

Graphene-based sponge is a novel hemostatic material prepared by chemical cross-link of graphene oxide. It has a fast fluid absorption capacity to quickly absorb blood from wounds, activate clotting pathways, and achieve rapid hemostasis. In addition, graphene-based sponge is also a good platform carrier.It can be prepared by organic cross-linking, compounding with inorganic clay, and adding bioactive factors to enhance coagulation stimulation. By these methods, the hemostatic performance of the...     

Rapid hemostasis and excellent antibacterial cerium-containing mesoporous bioactive glass/chitosan composite sponge for hemostatic material

Rapid and effective hemostasis is key to controlling bleeding and reducing mortality. Here, a composite hemostatic sponge (Ce-MBG/CHT) of cerium-containing mesoporous bioactive glass (Ce-MBG) and chitosan (CHT) was prepared by a freeze-drying technique and compared with the commercially available gelatin sponge (GS), to further evaluate the hemostatic performance of composite sponge materials. The results indicate that the pore structure, porosity, and water absorption of the sponge improved following the addition of Ce-MBG. Whole blood coagulation studies suggested that Ce-MBG/CHT has superior hemostatic properties to GS and validated in vitro thrombosis, platelet adhesion and blood compatibility. In vitro coagulation studies showed that factor XII was activated by the addition of Ce-MBG, inducing the intrinsic coagulation pathway. Furthermore, we evaluated the cytocompatibility of samples after contact with L929 cells for 24, 48, and 72 h via the cytotoxicity test. Compared with GS, 4Ce-MBG/CHT was more efficient against E. coli and S. aureus. All these results indicate that Ce-MBG/CHT sponges are likely useful for rapid hemostasis.     

Metal oxide surface charge mediated hemostasis

Blood coagulates faster upon contact with polar glasslike surfaces than on nonpolar plastic surfaces; this phenomenon is commonly termed the glass effect. However, the variable hemostatic response that we report here for contact-activated coagulation by different metal oxides, all of which are polar substrates, requires a refinement of this simple polarity model of how inorganic metal oxides activate the intrinsic pathway of blood coagulation. To our knowledge, the role of metal oxide surface charge as determined at the physiological pH and Ca2+ concentration of blood has not been previously investigated. We find that basic oxides with an isoelectric point above the pH of blood are anticoagulant while acidic oxides with an isoelectric point below the pH of blood are procoagulant. Using a thromboelastograph, we find that the onset time for coagulation and rate of coagulation post-initiation depend on both the sign and the magnitude of the initial surface charge density of the metal oxide. This work presents a useful strategy based on a quantifiable material parameter to select metal oxides to elicit a predictable and tunable biological response when they are in contact with blood.     

X‐ray microanalysis in STEM of short‐term physicochemical reactions at bioactive glass particle/biological fluid interface. Determination of O/Si atomic ratios

Short‐term physicochemical reactions at the interface between bioactive glass particles and biological fluids are studied and we focus our attention on the measurements of O/Si atomic ratio. The studied bioactive glass is in the SiO₂? Na₂O? CaO? P₂O₅? K₂O? Al₂O₃? MgO system. The elemental analysis is performed at the submicrometre scale by scanning transmission electron microscopy associated with energy‐dispersive x‐ray spectroscopy (EDXS) and electron energy‐loss spectroscopy (EELS). We previously developed an EDXS quantification method based on the ratio method and taking into account local absorption corrections. In this way, we use EELS data to determine, by an iterative process, the local mass thickness, which is an essential parameter for correcting absorption in EDXS spectra. After different immersion times of bioactive glass particles in a simulated biological solution, results show the formation of different surface layers at the bioactive glass periphery. Before 1 day of immersion, we observe the presence of an already shown (Si,O,Al)‐rich layer at the periphery. In this paper, we demonstrate that a thin ‘electron dense’ (Si,O)‐layer is formed on top of the (Si,O,Al)‐layer. In this (Si,O)‐layer, depleted in aluminium, we point out an increase of oxygen weight concentration that can be interpreted by the presence of Si(OH)₄ groups, which permit the formation of a (Ca,P)‐layer. Aluminium plays a role in the glass solubility and may inhibit apatite nucleation. After the beginning of the (Ca,P)‐layer formation, the size of the ‘electron dense’ (Si,O)‐layer decreases and tends to disappear. After 2 days of immersion, the (Ca,P)‐layer grows in thickness and leads to apatite precipitation. Copyright © 2004 John Wiley & Sons, Ltd.     

溶胶-凝胶生物活性玻璃在SBF中反应的形貌特征

The sol-gel derived bioactive glass in the system CaO-P2O5 -SiO2 was prepared using sol-gel technology and the porous bioactive material as bone defects filler and bone tissue engineering scaffold was made from the solgel bioactive glass powder through sintering. The crystalline phases,microstructure and bioactiviity of the sintered porous material was investigated using XRD、SEM and FTIR techniques and in vitro method. It was indicated that a few Ca5（PO4）2SiO4 （ 5CPS）crystals had been formed in the porous material during sintering at 800℃ for 5 min. In the simulated body fluid（SBF）,as the reaction progressed,the originally formed amorphous-phosphorus compound on the surface of glass mineralized hydroxy-carbonate-apatite（HCA）nanometer cluster,and interfused mutually until the HCA covering was formed. HCA crystallites only formed on the glass-phase. No HCA crystal was formed on the surface of 5CPS.     

Carbonate formation on bioactive glasses

The system termed 58S is a sol-gel-synthesized bioactive glass composed of SiO2, CaO, and P2O5, used in medicine as bone prosthetic because, when immersed in a physiological fluid, a layer of hydroxycarbonate apatite is formed on its surface. The mechanism of bioactive glass 58S carbonation was studied in the vacuum by means of in-situ FTIR spectroscopy with the use of CO2, H2O, and CD3CN as probe molecules. The study in the vacuum was necessary to identify both the molecules specifically involved in the carbonation process and the type of carbonates formed. Bioactive glass 58S was compared to a Ca-doped silica and to CaO. On CaO, ionic carbonates could form by contact with CO2 alone, whereas on 58S and on Ca-doped silica carbonation occurred only if both CO2 and an excess of H2O were present on the sample. The function of H2O was not only to block surface cationic sites, so that CO2 could not manifest its Lewis base behavior, but also to form a liquid-like (mono)layer that allowed the formation of carbonate ions. The presence of H2O is also supposed to promote Ca2+ migration from the bulk to the surface. Carbonates formed at the surface of CaO and of Ca-bearing silicas (thus including bioactive glasses) are of the same type, but are produced through two different mechanisms. The finding that a water excess is necessary to start heavy carbonation on bioactive glasses seemed to imply that the mechanism leading to in-situ carbonation simulates, in a simplified and easy-to-reproduce system, what happens both in solution, when carbonates are incorporated in the apatite layer, and during sample shelf-aging.     

Structural effects of phosphorus inclusion in bioactive silicate glasses

Molecular dynamics simulations of four bioactive silicate glasses containing between 0 (P0) and 12 (P12) mol % P2O5 have been carried out in order to elucidate the structural role of phosphorus in these materials. In particular, we have focused on structural features which can have a direct role in the bioactive mechanism of dissolution and bone bonding. The higher affinity of modifier Na and Ca cations for coordinating phosphate rather than silicate, together with the formation of P-O-Si linkages, lead to increasing repolymerization of the silicate network with increasing P2O5 content, which in principle would represent a negative effect of P inclusion on the glass bioactivity. However, this effect is counterbalanced by the concomitant increase in the amount of free orthophosphate groups, whose fast release is deemed to enhance the bioactivity. The strong affinity of the orthophosphates for calcium ions leads to a clear tendency toward separation of silicate-rich and phosphate-rich phases for the P12 composition. Although this could reduce the bioactivity in the case of P12, in general, the favorable balance between the effects mentioned above should result in a positive effect of partial Si --> P substitution on the glass bioactivity.     

Removal of residual nitrate ion from bioactive calcium silicate through soaking

Bioactive calcium silicates prepared by sol–gel routes mainly use calcium nitrate as the calcium precursor. However, the toxic nitrate ions are usually removed by calcination(i.e. 550 8C or over), which poses great challenge for the in situ preparation of inorganic/polymer composites, as polymer moieties could not survive such temperatures. In this study, we prepared 70Si30Ca(70 mol% Si O_2 and 30 mol%Ca O) bioactive glass at low temperatures where polymer could survive(i.e. 200 8C and 350 8C), and proposed to remove the residual nitrate ions through soaking. Deionized water and simulated body fluid(SBF) were employed as the soaking medium. The results showed that the residual nitrate ions could be removed as quickly as 0.5 h while maintain the bioactivity of the samples. This technique may open the possibility of preparing sol–gel derived bioactive glass/polymer hybrids in situ with reduced potential toxicity.     

Bioactive Gel Coatings Derived from Vinyltrimethoxysilane

An ethanol (EtOH) solution of polymerized vinyltrimethoxysilane (VTMS), about 20-mers, was mixed with an aqueous solution of calcium acetate (Ca(OAc)2) and refluxed in N2 for 1 h to give sols of a typical composition VTMS : H2O : EtOH : Ca(OAc)2 = 1 : 9 : 8 : 0.05 (mol). Homogeneous films could be produced, by dip-coating, on Nylon6® and soda-lime glass, but not on polypropylene or polytetrafluoroethylene. The gel films did not deposit apatite within 14 days of soaking in a simulated body fluid whereas films abraded with emery paper as well as bulk gels deposited apatite on the surfaces within 7 days, indicating the present gel was suitable for bioactive coatings on Nylon6®     

以滤纸为模板合成新型介孔生物活性玻璃微管材料

用快速滤纸为生物模板,通过先浸渍后焙烧的方法合成了介孔生物活性玻璃微管材料。快速滤纸的管状结构被完美复制,其管壁为生成的介孔生物玻璃材料。通过在合成过程中引入铁元素可以使材料具有一定的磁性。材料的形貌、结构和磁性通过扫描电镜、粉末X射线衍射、透射电镜、氮气吸附-脱附曲线,红外光谱和磁滞回线进行了表征。并且通过模拟体液浸泡方法考察了其矿化能力,以地塞米松为模型药物考察其释药能力和生物相容性。合成的介孔生物活性玻璃微管材料具有复杂的管状多级结构、快速的矿化能力和良好的生物相容性,并具备一定的磁性,是一种不可多得的药物缓释材料。     

以滤纸为模板合成新型介孔生物活性玻璃微管材料

用快速滤纸为生物模板,通过先浸渍后焙烧的方法合成了介孔生物活性玻璃微管材料。快速滤纸的管状结构被完美复制,其管壁为生成的介孔生物玻璃材料。通过在合成过程中引入铁元素可以使材料具有一定的磁性。材料的形貌、结构和磁性通过扫描电镜、粉末X射线衍射、透射电镜、氮气吸附-脱附曲线,红外光谱和磁滞回线进行了表征。并且通过模拟体液浸泡方法考察了其矿化能力,以地塞米松为模型药物考察其释药能力和生物相容性。合成的介孔生物活性玻璃微管材料具有复杂的管状多级结构、快速的矿化能力和良好的生物相容性,并具备一定的磁性,是一种不可多得的药物缓释材料。     

Mineral formation on dentin induced by nano-bioactive glass

The object of this study was to evaluate the effect of bioactive glass (BG) size on mineral formation on dentin surfaces. Totally demineralized dentin discs were treated using BG suspensions with different particle sizes:i.e., microscale bioactive glass (m-BG), submicroscale bioactive glass (sm-BG) and nanoscale bioactive glass (n-BG). Field-emission scanning electron microscopy and 3D profile measurement laser microscopy were used to observe the surface morphology and roughness. It was found that all BG particles could promoted mineral formation on dentin surfaces, while plug-like depositions were observed on the dentin discs treated by n-BG and they were more acid-resistant. The present results may imply that n-BG has potential clinical application for dentin hypersensitivity treatment.     

Low Temperature Synthesis,Structure and Bioactivity of 2CaO⋅3SiO2 Glass

Glasses of composition 2CaO3SiO₂ were prepared by means of the sol-gel route starting from tetramethyl orthosilicate and calcium nitrate tetrahydrate and the melt-quenching technique from a mixture of oxides. Their structures were compared. The infrared spectra suggest that the gel derived glass has a different structure than the corresponding melt quenched glass, having a more uniform distribution of non-bridging oxygens among the SiO₄ tetrahedra. Owing to its porosity, the gel derived glass is more prone to devitrify than the melt quenched glass is. The infrared spectra relative to samples soaked in a fluid simulating the composition of the human blood plasma suggest that the gel derived glass is more bioactive than the melt quenched glass is.     

87Sr solid-state NMR as a structurally sensitive tool for the investigation of materials: antiosteoporotic pharmaceuticals and bioactive glasses

Strontium is an element of fundamental importance in biomedical science. Indeed, it has been demonstrated that Sr(2+) ions can promote bone growth and inhibit bone resorption. Thus, the oral administration of Sr-containing medications has been used clinically to prevent osteoporosis, and Sr-containing biomaterials have been developed for implant and tissue engineering applications. The bioavailability of strontium metal cations in the body and their kinetics of release from materials will depend on their local environment. It is thus crucial to be able to characterize, in detail, strontium environments in disordered phases such as bioactive glasses, to understand their structure and rationalize their properties. In this paper, we demonstrate that (87)Sr NMR spectroscopy can serve as a valuable tool of investigation. First, the implementation of high-sensitivity (87)Sr solid-state NMR experiments is presented using (87)Sr-labeled strontium malonate (with DFS (double field sweep), QCPMG (quadrupolar Carr-Purcell-Meiboom-Gill), and WURST (wideband, uniform rate, and smooth truncation) excitation). Then, it is shown that GIPAW DFT (gauge including projector augmented wave density functional theory) calculations can accurately compute (87)Sr NMR parameters. Last and most importantly, (87)Sr NMR is used for the study of a (Ca,Sr)-silicate bioactive glass of limited Sr content (only ~9 wt %). The spectrum is interpreted using structural models of the glass, which are generated through molecular dynamics (MD) simulations and relaxed by DFT, before performing GIPAW calculations of (87)Sr NMR parameters. Finally, changes in the (87)Sr NMR spectrum after immersion of the glass in simulated body fluid (SBF) are reported and discussed.     

Paper-based device for rapid typing of secondary human blood groups

We report the use of bioactive paper for typing of secondary human blood groups. Our recent work on using bioactive paper for human blood typing has led to the discovery of a new method for identifying haemagglutination of red blood cells. The primary human blood groups, i.e., ABO and RhD groups, have been successfully typed with this method. Clinically, however, many secondary blood groups can also cause fatal blood transfusion accidents, despite the fact that the haemagglutination reactions of secondary blood groups are generally weaker than those of the primary blood groups. We describe the design of a user-friendly sensor for rapid typing of secondary blood groups using bioactive paper. We also present mechanistic insights into interactions between secondary blood group antibodies and red blood cells obtained using confocal microscopy. Haemagglutination patterns under different conditions are revealed for optimization of the assay conditions.     

Bioactive Glasses—Structure and Properties

Bioactive glasses were the first synthetic materials to show bonding to bone, and they are successfully used for bone regeneration. They can degrade in the body at a rate matching that of bone formation, and through a combination of apatite crystallization on their surface and ion release they stimulate bone cell proliferation, which results in the formation of new bone. Despite their excellent properties and although they have been in clinical use for nearly thirty years, their current range of clinical applications is still small. Latest research focuses on developing new compositions to address clinical needs, including glasses for treating osteoporosis, with antibacterial properties, or for the sintering of scaffolds with improved mechanical stability. This Review discusses how the glass structure controls the properties, and shows how a structure‐based design may pave the way towards new bioactive glass implants for bone regeneration.     

Poly(γ‐glutamic acid)/Silica Hybrids with Calcium Incorporated in the Silica Network by Use of a Calcium Alkoxide Precursor

Current materials used for bone regeneration are usually bioactive ceramics or glasses. Although they bond to bone, they are brittle. There is a need for new materials that can combine bioactivity with toughness and controlled biodegradation. Sol‐gel hybrids have the potential to do this through their nanoscale interpenetrating networks (IPN) of inorganic and organic components. Poly(γ‐glutamic acid) (γ‐PGA) was introduced into the sol‐gel process to produce a hybrid of γ‐PGA and bioactive silica. Calcium is an important element for bone regeneration but calcium sources that are used traditionally in the sol‐gel process, such as Ca salts, do not allow Ca incorporation into the silicate network during low‐temperature processing. The hypothesis for this study was that using calcium methoxyethoxide (CME) as the Ca source would allow Ca incorporation into the silicate component of the hybrid at room temperature. The produced hybrids would have improved mechanical properties and controlled degradation compared with hybrids of calcium chloride (CaCl₂), in which the Ca is not incorporated into the silicate network. Class II hybrids, with covalent bonds between the inorganic and organic species, were synthesised by using organosilane. Calcium incorporation in both the organic and inorganic IPNs of the hybrid was improved when CME was used. This was clearly observed by using FTIR and solid‐state NMR spectroscopy, which showed ionic cross‐linking of γ‐PGA by Ca and a lower degree of condensation of the Si species compared with the hybrids made with CaCl₂ as the Ca source. The ionic cross‐linking of γ‐PGA by Ca resulted in excellent compressive strength and reduced elastic modulus as measured by compressive testing and nanoindentation, respectively. All hybrids showed bioactivity as hydroxyapatite (HA) was formed after immersion in simulated body fluid (SBF).     

Influence of particle size on the crystallization process and the bioactive behavior of a bioactive glass system

Bioactive glasses have attracted considerable interest in recent years, due to their technological application, especially in biomaterials research. Differential scanning calorimetry (DSC) has been used in the study of the crystallization mechanism in the SiO₂–Na₂O–CaO–P₂O₅ glass system, as a function of particle size. The curve of the bulk glass presents a slightly asymmetric crystallization peak that could be deconvoluted into two separate peaks, their separation being followed in the form of powder glasses. Also, a shift of the crystallization peaks to lower temperatures was observed with the decrease of the particle size. FTIR studies – that are confirmed by XRD measurements – proved that the different peaks could be attributed to different crystallization mechanisms. Moreover, it is presented the bioactive behavior of the specific glass as a function of particle size. The study of bioactivity is performed through the process of its immersion in simulated human blood plasma (simulated body fluid, SBF) and the subsequent examination of the development of carbonate-containing hydroxyapatite layer on the surface of the particles. The bioactive response is improved with the increase of the particle size of powders up to 80 μm and remains almost unchanged for further increase, following the specific surface to volume ratio decrease.     

Smart Soft‐Templating Synthesis of Hollow Mesoporous Bioactive Glass Spheres

Hollow bioactive glass spheres with mesoporous shells were prepared by using dual soft templates, a diblock co‐polymer poly(styrene‐b‐acrylic acid) (PS‐b‐PAA) and a cationic surfactant cetyltrimethylammonium bromide (CTAB). Hollow mesoporous bioactive glass (HMBG) spheres comprise the large hollow interior with vertical mesochannels in shell, which realize large uptake of drugs and their sustained release. The formation of hydroxyapatite layer on the surface of HMBG particles shows the clear evidence for promising application in bone regeneration.     

The influence of cobalt incorporation and cobalt precursor selection on the structure and bioactivity of sol–gel-derived bioactive glass

Cobalt (Co) is a potential therapeutic ion used to enhance angiogenesis through a stabilizing effect on hypoxia-inducible factor 1 alpha (HIF-1α), and its incorporation into the structure of bioactive glass is a promising strategy to enable sustained local delivery of Co to a wound site or bone defect. Here Co-releasing bioactive glasses were obtained through the sol–gel method, comparing cobalt nitrate and cobalt chloride as precursors. The effect of using different Co precursors on the sol–gel synthesis and in the obtained bioactive glass structure, chemical composition, morphology, dissolution behaviour, hydroxycarbonate apatite (HCA) layer formation was investigated. When the chloride salt was used as Co precursor, evidence of crystalline cobalt (II, III) oxide (Co₃O₄) phase formation was found, along with the presence of Co³⁺ species as evaluated by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), whereas an amorphous glass containing mainly Co²⁺ species was obtained when the nitrate salt was the Co source. The presence of a crystalline phase decreased the surface area and pore volume of the final glass, consequently reducing the Co-release rate. Evidence of HCA layer formation after immersion in simulated body fluid (SBF) was still found when different precursors were used, although the rate of formation was reduced by the presence of Co. Therefore, this study showed that Co incorporation and the proper selection of the precursor could affect the final material structure, and properties, and should be considered when designing new bioactive glass compositions for tissue engineering applications.

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