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In previous works, we reported the fabrication of cotton-wool-like composites consisting of siloxane-doped vaterite and poly(L-lactic acid) (SiVPCs). Various irregularly shaped bone voids can be filled with the composite, which effectively supplies calcium and silicate ions, enhancing the bone formation by stimulating the cells. The composites, however, were brittle and showed an initial burst release of ions. In the present work, to improve the mechanical flexibility and ion release, the composite fiber was coated with a soft, thin layer consisting of poly(D,L-lactic-co-glycolic acid) (PLGA). A coaxial electrospinning technique was used to prepare a cotton-wool-like material comprising "core-shell"-type fibers with a diameter of ∼12 μm. The fibers, which consisted of SiVPC coated with a ∼2-μm-thick PLGA layer, were mechanically flexible; even under a uniaxial compressive load of 1.5 kPa, the cotton-wool-like material did not exhibit fracture of the fibers and, after removing the load, showed a ∼60% recovery. In Tris buffer solution, the initial burst release of calcium and silicate ions from the "core-shell"-type fibers was effectively controlled, and the ions were slowly released after one day. Thus, the mechanical flexibility and ion-release behavior of the composites were drastically improved by the thin PLGA coating. [ABSTRACT FROM AUTHOR]

Poly(L-lactic acid)-based films which include 60 wt % of vaterite (V) or siloxane-containing vaterite (SiV) were coated on a pure magnesium substrate, denoted by PLLA/V or PLLA/SiV, respectively, to suppress early corrosion and improve its cytocompatibility. Both coating films adhered to the Mg substrate with 2.3-2.8 MPa of tensile bonding strength. Soaking test for 7 days in α-modified minimum essential medium revealed that the morphological instability of the PLLA/V film caused a higher amount of Mg2+ ion to be released from the coating sample. On the other hand, in the case of the coating with the PLLA/SiV film, no morphological change even after the soaking test was observed, owing to the suppression of the degradation rate. In cell culture tests, the proliferation of mouse osteoblast-like cell (MC3T3-E1) was significantly enhanced by both coatings, in comparison with the uncoated magnesium substrate. The cell morphology revealed that a few less-spread cells were observed on the PLLA/V film, while more elongated cells were done on the PLLA/SiV film. The cells on the PLLA/SiV film exhibited an extremely higher alkaline phosphatase activity after 21 days of incubation than that on the PLLA/V one. The PLLA/SiV film suppressed the early corrosion and enhanced cytocompatibility on metallic magnesium. [ABSTRACT FROM AUTHOR]

Phosphate glasses in the 50 CaO-(50-x) P2O5- xTi O2-1 Al2O3 (x = 5-25 mol%) system were produced and irradiated with low energy density CO2 laser to melt and crystallize on a hydroxyapatite ( HA) ceramic plate for dental filler applications. The laser with 10.6 μm of wavelength is easily absorbed by phosphate and hydroxy groups. The phosphate glasses containing ~15 mol% of titania strongly adhered to the HA plate surface through melting and sintering by the laser irradiation. The coatings after the laser irradiation contained crystalline phases. There was no significant changes in the morphology of the coating containing 15 mol% of TiO2 on the HA plate even after soaking in 0.1 m M HCl solution for 10 min. This coating was suspected to have good chemical durability. Powders of the glass or glass-ceramic containing 15 mol% of TiO2 were soaked in distilled water to check their dissolution behavior over the long term. Dissolution from the glass-ceramic was much slower than those from the glass at all points. [ABSTRACT FROM AUTHOR]

Stroke survivors majorly suffered from post-stroke depression (PSD). The PSD diagnosis is commonly performed based on the clinical cut-off for psychometric inventories. However, we hypothesized that PSD involves spectrum symptoms (e.g., apathy, depression, anxiety, and stress domains) and severity levels. Therefore, instead of using the clinical cut-off, we suggested a data-driven analysis to interpret patient spectrum conditions. The patients' psychological conditions were categorized in an unsupervised manner using the k-means clustering method, and the relationships between psychological conditions and quantitative lesion degrees were evaluated. This study involved one hundred sixty-five patient data; all patients were able to understand and perform self-rating psychological conditions (i.e., no aphasia). Four severity levels—low, low-to-moderate, moderate-to-high, and high—were observed for each combination of two psychological domains. Patients with worse conditions showed the significantly greater lesion degree at the right Rolandic operculum (part of Brodmann area 43). The dissimilarities between stress and other domains were also suggested. Patients with high stress were specifically associated with lesions in the left thalamus. Impaired emotion processing and stress-affected functions have been frequently related to those lesion regions. Those lesions were also robust and localized, suggesting the possibility of an objective for predicting psychological conditions from brain lesions. [ABSTRACT FROM AUTHOR]

To mimic the structure and composition of the natural bone extracellular matrix (ECM), fibrous hybrid scaffolds were prepared by electrospinning a sol–gel derived mixture of poly(γ-glutamic acid) (γ-PGA) and hydrolyzed tetraethylorthosilicate (TEOS). The introduction of NaHCO 3 caused the formation of the sodium salt form of γ-PGA, making the polymer soluble in aqueous-based solution. To improve the stability of electrospun γ-PGA-silica hybrid scaffolds under physiological environment, 3-glycidoxypropyl trimethoxysilane (GPTMS) was employed as a coupling agent to link γ-PGA and silanols of the hydrolyzed TEOS. The effect of the TEOS content on the physicochemical properties of the electrospun hybrid scaffolds, such as morphology, microstructure, mechanical behavior, degradation, as well as in vitro biocompatibility were investigated. The resultant fibers revealed a uniform morphology with the increased mean diameter as the content of TEOS increased. The results of FTIR and 29 Si MAS-NMR indicated that γ-PGA and silica networks were successfully covalent-linked in the presence of GPTMS. All of these electrospun hybrid scaffolds showed stable soluble silica release without any initial burst release in Tris–HCl buffer solution and the content of released silicon can also be adjusted by the TEOS content. In addition, the tensile mechanical performances, thermal stability, and in vitro proliferation and ALP activity of fibrous scaffolds were effectively improved by the increasing TEOS content. The results suggest that the γ-PGA-silica hybrid scaffolds with tailorable physiochemical properties can provide an excellent ECM for bone tissue regeneration. [ABSTRACT FROM AUTHOR]

MgO–CaO–P 2 O 5 –Nb 2 O 5 glasses with the substitution of MgO for CaO consisting predominantly of meta-, pyro-, and orthophosphate groups were prepared using a melt-quenching method, and their structures and dissolution behaviors were investigated. Magnesium in the metaphosphate compositions was shown to act as a modifier oxide and coordinate phosphate groups. Magnesium in the pyro- and/or orthophosphate compositions was shown to act as a network former and to form P–O–Mg bonds, which crosslink short phosphate groups. The chemical durability of the metaphosphate glasses increased with increasing the substitution of MgO for CaO because magnesium exhibits a larger field strength than calcium. However, the durability of the pyro- and/or orthophosphate glasses decreased with increasing the MgO content: P–O–Mg bonds weakened the glass network structure and induced hydrolysis. [ABSTRACT FROM AUTHOR]

Common phosphate glasses—for example, those in the metaphosphate region—show potential as biodegradable materials. Some applications, such as biocompatible thin films coated on titanium or its alloys using radiofrequency magnetron sputtering methods, require films with good chemical durability. In the present work, CaO–P 2 O 5 –TiO 2 /Nb 2 O 5 glasses with a Ca/P ratio of ≥ 1.00 were prepared using a melt-quenching method, and their structures and dissolution behaviors were investigated. When the Ca/P ratio was increased, the amount of orthophosphate ( Q p 0 ) group in the glasses increased, and that of pyrophosphate ( Q p 1 ) group decreased. The amount of Q p 0 group was greater than the amount of Q p 1 groups in glasses with a Ca/P ratio of ≥ 1.14. Intermediate oxides (i.e., TiO 2 and Nb 2 O 5 ) in the glasses cross-linked with the phosphate groups to form P–O–Ti/Nb bonds; these bonds were expected to take a tetrahedral form. The glasses prepared in the present work showed excellent chemical durability, because of the P–O–Ti/Nb bonds and the delocalized P O bonds that resulted from the increasing Q p 0 content in the glasses. [ABSTRACT FROM AUTHOR]

• β -tricalcium phosphate mechanochemically amorphized in a short time. • Ball milling performed using small zirconia beads and acetone. • Amorphous phase of calcium orthophosphate obtained. • Amorphized particles released large amounts of calcium and phosphate ions. Increasing the amounts of calcium and phosphate ions released in vivo by β -tricalcium phosphate (β -TCP) may enhance its osteogenic activity for bone repair and regeneration. Planetary ball milling of β -TCP powder using acetone and 1-mm-diameter zirconia beads reduced the average particle size of the powder to ∼ 0.4 µm within 120 min and converted most of the crystals to an amorphous phase of calcium orthophosphate. Immersing the treated powder in a tris-HCl buffered solution of pH 7.4 for 24 h at 37 °C dissolved calcium and phosphate ions with several times the yield from that of the original β -TCP powder. This approach is expected to be useful for preparing composite materials with an enhanced therapeutic effect on living tissues. [ABSTRACT FROM AUTHOR]

Abstract: A common issue in blood-related brain-function measurements, such as optical topography, is that the observed signals are usually corrupted with strong noise that is primarily spontaneous low-frequency oscillations (LFOs) in cerebral hemodynamics, which are difficult to separate from the signals due to functional brain activity because of their common spectral range. We discuss the analysis of information transfer between LFOs around 0.1 Hz in the hemoglobin concentration change (HbCC) in the cerebral cortex, the heart rate (HR), and the mean arterial blood pressure (ABP) to understand the origin of spontaneous LFOs in cerebral hemodynamics. As measures of information transfer, we used transfer entropy (TE) for two-variable system analysis and introduced intrinsic transfer entropy for further analysis of three-variable systems by extending the original TE. Data for analysis were obtained from simultaneous measurements with optical topography and infrared finger plethysmography under rest conditions. The analysis revealed that the LFOs in oxy HbCC, a parameter of cerebral hemodynamics, mainly stem from HR, but its contribution is only about 20%. In addition, the intrinsic contribution of ABP is about 5% and the common contribution of HR and ABP is about 10%. From these, HR and ABP cannot account for more than the half the information carried with variable oxy HbCC, which suggests the origin of LFOs in cerebral hemodynamics may lie in the regulation of regional cerebral blood flow change and energetic metabolism rather than due to the systemic regulation of the cardiovascular system. [Copyright &y& Elsevier]

Herein, we describe the successful construction of novel electrospun fibermats from the cross-linkable copolymer poly (acrylamide)- co -poly (diacetone acrylamide) ( PAM- co -PDAAM ) with the molar ratio of acrylamide and diacetone acrylamide units 8:2 ( PAM- co -PDAAM(8:2) ) by in situ cross-linking during electrospinning with the bifunctional cross-linker adipic dihydrazide (ADH). As the cross-linking reactions between the ketone groups in PAM- co -PDAAM(8:2) and the hydrazide groups in ADH (in pH 6–8 aqueous buffer) is one of the bio-orthogonal reactions that are inert for various functional groups in biomacromolecules, stable encapsulation of green fluorescent protein and α-chymotrypsin at the inside of constituent nanofibers was successfully achieved without losing the original biological activities. Aqueous buffer is the only solvent through all process of fibermat construction, and combination of bioorthogonal reactions is optimum for the construction of fibermats that encapsulate biomacromolecules. The examples presented in this study should provide fascinating insight for future biomacromolecule-encapsulated fibermat research. [ABSTRACT FROM AUTHOR]

Calcium phosphate glasses were prepared by adding Nb 2 O 5 and Na 2 O. Spectroscopic analyses showed that the glasses included niobate groups, such as NbO 4 and NbO 6 . The amount of NbO 4 units, which was considered to be a network former, increased with the increase in Nb 2 O 5 content, and the formation of an Nb–O–P bond appeared. The ion-releasing ability of the glasses in the Tris-buffer solution depended on their chemical composition. The process window of the glass, which was estimated from the temperature range between the glass transition and the onset of crystallization, increased with the increase of the Nb 2 O 5 content of the glass. The excellent chemical durability and glass-forming ability of calcium phosphate glass were considered to originate from the formation of the Nb–O–P bond. [ABSTRACT FROM AUTHOR]

Abstract: Functional magnetic resonance imaging (fMRI) is an important tool for noninvasively imaging the hemodynamic responses accompanying brain activity, but fMRI measurements are accompanied by loud acoustic noises resulting from Lorentz forces that cannot be completely excluded when the present technology is used. We used recorded fMRI acoustic noise and examined its effect on sensorimotor activation in optical topography measurement when subjects were instructed to tap the fingers of the right hand under a 23-dB non-noise condition and 46-, 56-, and 65-dB noise conditions. The results showed that the amplitude of the activation signal (relative change in concentration) for oxygenated hemoglobin in the sensorimotor cortex decreased with increasing noise. The activation signal for deoxygenated hemoglobin did not depend significantly on the noise level but did tend to decrease with increasing noise. These results suggest that fMRI acoustic noise affects the hemodynamics of cortical areas associated with the processing of information other than auditory information. [Copyright &y& Elsevier]

• A novel zinc-containing phosphate amorphous thin film was successfully prepared. • The film consists predominantly of ortho- and pyrophosphate groups. • The film showed excellent anitibacterial activities. • The film showed no cytotoxicity to osteoblast-like cells. A zinc phosphate invert glass consisting of orthophosphate and pyrophosphate groups, with a composition of 65ZnO–30P 2 O 5 –5Nb 2 O 5 in mol%, showed antibacterial activity that provides biological safety owing to its well-controlled Zn2+ ion-releasing behavior. In the present work, in order to fundamentally understand the possibility of using bio-functional coating on dental implant surfaces, a glassy thin film was deposited on silica glass or a metallic titanium substrate by radiofrequency magnetron sputtering using the 65ZnO–30P 2 O 5 –5Nb 2 O 5 glass as the target material. The resultant coating was an amorphous thin film consisting of orthophosphate and pyrophosphate groups with a trace amount of a metaphosphate group. Although the amounts of orthophosphate and pyrophosphate groups in the film were smaller and larger, respectively, than those in the target glass, the condensation of these phosphate groups could be controlled to a trace amount even during the deposition. The thin film showed effective antibacterial activities against Gram-negative and -positive bacteria without cytotoxicity to osteoblast-like cells. The thickness of the film after being soaked in a Tris buffer solution reduced gradually with a ratio of ~10 nm/d; thus, it showed a relatively-high durability. [ABSTRACT FROM AUTHOR]

The development of a new materials platform capable of sustaining the functionality of proteinous sensor molecules over an extended period without being affected by biological contaminants in living systems, such as proteases, is highly demanded. In this study, our primary focus was on fabricating new core-shell fibremats using unique polymer materials, capable of functionalizing encapsulated sensor proteins while resisting the effects of proteases. The core-fibre parts of core-shell fibremats were made using a newly developed post-crosslinkable water-soluble copolymer, poly(2-hydroxypropyl methacrylamide)- co -poly(diacetone methacrylamide), and the bifunctional crosslinking agent, adipic dihydrazide, while the shell layer of the nanofibers was made of nylon 6. Upon encapsulating the lactate-sensor protein eLACCO1.1 at the core-fibre part, the fibremat exhibited a distinct concentration-dependent fluorescence response, with a dynamic range of fluorescence alteration exceeding 1000% over the lactate concentration range of 0 to 100 mM. The estimated dissociation constant from the titration data was comparable to that estimated in a buffer solution. The response remained stable even after 5 cycles and in the presence of proteases. These results indicates that our core-shell fibremat platform could serve as effective immobilizing substrates for various sensor proteins, facilitating continuous and quantitative monitoring of various low-molecular-weight metabolites and catabolites in a variety of biological samples., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Core-shell fibremats, comprising poly(acrylamide)- co -poly(diacetone-acrylamide)/adipic dihydrazide [poly(AM/DAAM)/ADH] core-nanofibres and hydrophobic polymer shell layers, are a new class of platforms for constructing various immobilised enzymes. In this study, to elucidate the impacts of the shell-layer material on fibremat properties and enzymatic activities, we synthesised core-shell fibremats with shell layers comprising nylon6 or acetyl cellulose (AcCel) instead of poly(ε-caprolactone) (PCL), as in our previous study. Transmission and scanning electron microscopy images revealed that the lactase-encapsulated poly(AM/DAAM)/ADH-nylon6 and -AcCel fibremats were both constructed like the poly(AM/DAAM)/ADH-PCL one. Leakage measurements of the beforehand loaded molecules inside the core-nanofibres revealed that both fibremats exhibited efficient permeability for low-molecular-weight molecules and stable retention of enzyme molecules inside the core-nanofibres. Meanwhile, the fibremats' mechanical properties considerably depended on the choice of shell-layer material. The thermal analyses of the lactase-encapsulated fibremats revealed residual water inside the core nanofibres. The core-shell fibremats fabricated with a nylon6 or PCL shell exhibited excellent enzymatic activities (102 and 114%, respectively, compared to that of free lactase), superior to that of the same amount of free enzyme in a buffer. Furthermore, both core-shell fibremats retained over 95% of their initial enzymatic activities, even after they were re-used 10 times., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Brain imaging is necessary for understanding disease symptoms, including stroke. However, frequent imaging procedures encounter practical limitations. Estimating the brain information (e.g., lesions) without imaging sessions is beneficial for this scenario. Prospective estimating variables are non-imaging data collected from standard tests. Therefore, the current study aims to examine the variable feasibility for modelling lesion locations. Heterogeneous variables were employed in the multivariate logistic regression. Furthermore, patients were categorized (i.e., unsupervised clustering through k-means method) by the charasteristics of lesion occurrence (i.e., ratio between the lesioned and total regions) and sparsity (i.e., density measure of lesion occurrences across regions). Considering those charasteristics in models improved estimation performances. Lesions (116 regions in Automated Anatomical Labeling) were adequately predicted (sensitivity: 80.0-87.5% in median). We confirmed that the usability of models was extendable to different resolution levels in the brain region of interest (e.g., lobes, hemispheres). Patients' charateristics (i.e., occurrence and sparsity) might also be explained by the non-imaging data as well. Advantages of the current approach can be experienced by any patients (i.e., with or without imaging sessions) in any clinical facilities (i.e., with or without imaging instrumentation)., (© 2022. The Author(s).)

Background: The Trail Making Test Part-B (TMT-B) is an attention functional test to investigate cognitive dysfunction. It requires the ability to recognize not only numbers but also letters. We analyzed the relationship between brain lesions in stroke patients and their TMT-B performance., Methods: From the TMT-B, two parameters (score and completion time) were obtained. The subjects were classified into several relevant groups by their scores and completion times through a data-driven analysis ( k -means clustering). The score-classified groups were characterized by low (≤10), moderate (10 < score < 25), and high (25) scores. In terms of the completion time, the subjects were classified into four groups. The lesion degree in the brain was calculated for each of the 116 regions classified by automated anatomical labeling (AAL). For each group, brain sites with a significant difference (corrected p < 0.1) between each of the 116 regions were determined by a Wilcoxon Rank-Sum significant difference test., Results: Lesions at the cuneus and the superior occipital gyrus, which are mostly involved in visual processing, were significant (corrected p < 0.1) in the low-score group. Furthermore, the moderate-score group showed more-severe lesion degrees (corrected p < 0.05) in the regions responsible for the linguistic functions, such as the superior temporal gyrus and the supramarginal gyrus. As for the completion times, lesions in the calcarine, the cuneus, and related regions were significant (corrected p < 0.1) in the fastest group as compared to the slowest group. These regions are also involved in visual processing., Conclusion: The TMT-B results revealed that the subjects in the low-score group or the slowest- group mainly had damage in the visual area, whereas the subjects in the moderate-score group mainly had damage in the language area. These results suggest the potential utility of TMT-B performance in the lesion site., Competing Interests: AN, SS, MK, HA, AO, TF, and AK were employed by Hitachi Ltd. TM was employed by Maxell Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nishimura, Sutoko, Kiguchi, Atsumori, Obata, Funane, Kandori, Mizuguchi, Shimonaga, Hama and Tsuji.)

Skin has excellent capacity to regenerate, however, in the event of a large injury or burn skin grafts are required to aid wound healing. The regenerative capacity further declines with increasing age and can be further exacerbated with bacterial infection leading to a chronic wound. Engineered skin substitutes can be used to provide a temporary template for the damaged tissue, to prevent/combat bacterial infection and promote healing. In this study, the sol-gel process and electrospinning were combined to fabricate 3D cotton-wool-like sol-gel bioactive glass fibers that mimic the fibrous architecture of skin extracellular matrix (ECM) and deliver metal ions for antibacterial (silver) and therapeutic (calcium and silica species) actions for successful healing of wounds. This study investigated the effects of synthesis and process parameters, in particular sintering temperature on the fiber morphology, the incorporation and distribution of silver and the degradation rate of fibers. Silver nitrate was found to decompose into silver nanoparticles within the glass fibers upon calcination. Furthermore, with increasing calcination temperature the nanoparticles increased in size from 3 nm at 600 °C to ~25 nm at 800 °C. The antibacterial ability of the Ag-doped glass fibers decreased as a function of the glass calcination temperature. The degradation products from the Ag-doped 3D non-woven sol-gel glass fibers were also found to promote fibroblast proliferation thus demonstrating their potential for use in skin regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A new concept, 'Layered mental healthcare' for keeping employees mental well-being in the workplace to avoid losses caused by both absenteeism and presenteeism is proposed. A key factor forming the basis of the concept is the biometric measurements over three layers, i.e., behaviour, physiology, and brain layers, for monitoring mental/distress conditions of employees. Here, the necessity of measurements in three layers was validated by the data-driven approach using the preliminary dataset measured in the office environment. Biometric measurements were supported by an activity tracker, a PC logger, and the optical topography; mental/distress conditions were quantified by the brief job stress questionnaire. The biometric features obtained 1 week before the measurement of mental/distress scores were selected for the best regression model. The feature importance of each layer was obtained in the learning process of the best model using the light graded boosting machine and was compared between layers. The ratio of feature importance of behaviour:physiology:brain layers was found to be 4:3:3. The study results suggest the contribution and necessity of the three-layer features in predicting mental/distress scores., (© 2021 The Authors. Healthcare Technology Letters published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.)

We have developed a system with multimodality that monitors objective biomarkers for screening the mental distress in the office. A field study using a prototype of the system was performed over four months with 39 volunteers. We obtained PC operation patterns using a PC logger, sleeping time and activity levels using a wrist-band-type activity tracker, and brain activity and behavior data during a working memory task using optical topography. We also administered two standard questionnaires: the Brief Job Stress Questionnaire (BJS) and the Kessler 6 scale (K6). Supervised machine learning and cross validation were performed. The objective variables were mental scores obtained from the questionnaires and the explanatory variables were the biomarkers obtained from the modalities. Multiple linear regression models for mental scores were comprehensively searched and the optimum models were selected from 2,619,785 candidates. Each mental score estimated with each optimum model was well correlated with each mental score obtained with the questionnaire (correlation coefficient = 0.6-0.8) within a 24% of estimation error. Mental scores obtained by means of questionnaires have been in general use in mental health care for a while, so our multimodality system is potentially useful for mental healthcare due to the quantitative agreement on the mental scores estimated with biomarkers and the mental scores obtained with questionnaires., (Copyright © 2020 Kiguchi, Sutoko, Atsumori, Nishimura, Obata, Funane, Nakagawa, Egi and Kuriyama.)

An electrospinning technique was used to produce three-dimensional (3D) bioactive glass fibrous scaffolds, in the SiO 2 -CaO sol-gel system, for wound healing applications. Previously, it was thought that 3D cotton wool-like structures could only be produced from sol-gel when the sol contained calcium nitrate, implying that the Ca 2+ and its electronic charge had a significant effect on the structure produced. Here, fibres with a 3D appearance were also electrospun from compositions containing only silica. A polymer binding agent was added to inorganic sol-gel solutions, enabling electrospinning prior to bioactive glass network formation and the polymer was removed by calcination. While the addition of Ca 2+ contributes to the 3D morphology, here we show that other factors, such as relative humidity, play an important role in producing the 3D cotton-wool-like macrostructure of the fibres. A human dermal fibroblast cell line (CD-18CO) was exposed to dissolution products of the samples. Cell proliferation and metabolic activity tests were carried out and a VEGF ELISA showed a significant increase in VEGF production in cells exposed to the bioactive glass samples compared to control in DMEM. A novel SiO 2 -CaO nanofibrous scaffold was created that showed tailorable physical and dissolution properties, the control and composition of these release products are important for directing desirable wound healing interactions.

In our previous study, we investigated the synergetic effects of inorganic ions, such as silicate, Mg 2+ and Ca 2+ ions on the osteoblast-like cell behaviour. Mg 2+ ions play an important role in cell adhesion. In the present study, we designed a new composite that releases a high concentration of Mg 2+ ions during the early stage of the bone-forming process, and silicate and Ca 2+ ions continuously throughout this process. Here, 40SiO 2 -40MgO-20Na 2 O glass (G) with high solubility and vaterite-based calcium carbonate (V) were selected as the source of silicate and Mg 2+ and Ca 2+ ions, respectively. These particles were mixed with poly(lactic- co -glycolic acid) (PLGA) using a kneading method at 110°C to prepare the composite (G-V/PLGA, G/V/PLGA = 4/56/40 (in weight ratio)). Most of the Mg 2+ ions were released within 3 days of immersion at an important stage for cell adhesion, and silicate and Ca 2+ ions were released continuously at rates of 70-80 and 180 ppm d -1 , respectively, throughout the experiment (until day 7). Mouse-derived osteoblast-like MC3T3-E1 proliferated more vigorously on G-V/PLGA in comparison with V-containing PLGA without G particles; it is possible to control the ion-release behaviour by incorporating a small amount of glass particles., Competing Interests: The authors declare we have no competing interests., (© 2019 The Authors.)

The increase in the number of patients with mental disorders with depressive symptoms has become a significant problem. To prevent people developing those disorders and help with the effective recovery, it is important to quantitatively and objectively monitor an individual's mental state. Previous studies have shown the relationship between negative or depressive mood state and human prefrontal cortex (PFC) activation during verbal and spatial working memory tasks based on a near-infrared spectroscopy imaging technique. In this study, we aimed to explore a biomarker of the mental state of people in remission of mental disorders with depressive symptoms using this technique. We obtained the PFC activation of return-to-work (RTW) trainees in remission of those disorders, compared that of healthy controls, and obtained subjective questionnaire scores with the Profile of Mood States. We compared the PFC activation with the questionnaire scores by receiver operating characteristic analysis using a logistic-regression model. The results showed that the PFC activation indicates a healthy state compared to that of the RTW trainees evaluated by area-under-curve analysis. This study demonstrates that our PFC measurement technique will be useful as a quantitative and objective assessment of mental state.

Combinatorial effects of three ions, namely silicate (Si), calcium (Ca), and magnesium (Mg) ions, on the adhesion and proliferation of MC3T3-E1 mouse osteoblast-like cells were evaluated. The cells were cultured in single-, dual-, or triple-ion-conditioned culture media with systematically changed ion concentrations. The ranges of Si, Ca, and Mg ion concentrations were set as 10-70, 80-400, and 25-500 ppm, respectively. The numbers of adherent live cells were measured after culturing for 3 h and for 1, 3, and 5 days to examine cell adhesion and proliferation, respectively. Mg ions predominantly enhanced cell adhesion in both the dual-ion (xSi-zMg and yCa-zMg) and triple-ion (xSi-yCa-zMg) systems but had no effect when they acted individually in the single-ion system. Conversely, Si ions predominantly enhanced cell proliferation in most single- and triple-ion-conditioned media. Evaluation of the combinatorial effects of the three ions on cell adhesion and proliferation revealed that the dual- and triple-ion-conditioned media mainly conferred synergistic effects on adhesion but antagonistic effects on proliferation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1042-1051, 2019., (© 2019 Wiley Periodicals, Inc.)

Protein-encapsulated fibermats are an attractive platform for protein-based bioactive materials. However, the choice of methods is still limited and not applicable to a wide range of proteins. In this study, we studied new polymeric materials for constructing protein-encapsulated fibermats, in which protein molecules are encapsulated within the nanofibers of fibermats without causing deleterious changes to protein structure or function. We constructed a protein-encapsulated fibermat using the poly(γ-glutamate) (PGA)/(3-glycidyloxypropyl)-trimethoxysilane (GPTMS) hybrid as a precursor for electrospinning. Because the PGA/GPTMS hybrid is water-soluble, protein molecules can be added to the precursor in an aqueous solution, significantly enhancing protein stability. Polycondensation during electrospinning (in-flight polycondensation) makes the obtained fibermats water-insoluble, which stabilizes the fibermat structure such that it is resistant to degradation in aqueous buffer. The molecular structure of the PGA/GPTMS hybrid gives rise to unique molecular permeability, which alters the selectivity and specificity of biochemical reactions involving the encapsulated enzymes; lower molecular-weight (MW) substrates can permeate the nanofibers, promoting enzyme activity, but higher MW substrates such as inhibitor peptides cannot permeate the nanofibers, suppressing enzyme activity. We present an effective method of encapsulating bioactive molecules while maintaining their structure and function, increasing the versatility of electrospun fibermats for constructing various bioactive materials.

Cotton wool-like poly(L-lactic acid) and siloxane-doped vaterite (SiV) composite scaffolds were prepared with a modified electrospinning system for bone tissue engineering applications. The effects of changing the SiV content in the materials from 10 to 30 wt% on elasticity and the ability to release calcium ions and soluble silica were evaluated. The elasticity of the cotton wool-like composites was almost the same as that of the PLLA from the results of compressibility and recovery tests. The materials released calcium ions for more than 56 days and soluble silica for 28-56 days in a tris buffer solution (pH 7.4). Mouse osteoblast-like cells (MC3T3-E1 cells) were cultured on/in the cotton wool-like materials or the fibremats out of the same composite materials as that used for the cotton wool-like materials. The cells penetrated into and proliferated inside the cotton wool-like materials, although they mainly adhered on the fibremat surface.

The effects of niobium ions released from 60CaO-30P(2)O(5)-(10-x)Na(2)O-xNb(2)O(5) (mol %, x = 0-10) glasses on MC3T3-E1 cell functions were evaluated by culture tests with two systems; cell culture on glass plates, or in culture media containing glass extracts. Alkaline phosphatase (ALP) activity in the cells cultured on the glass plates containing 3 and 5 mol % of Nb(2)O(5) was significantly higher than that on the Nb(2)O(5)-free glass, although proliferation was not enhanced on all glasses containing Nb(2)O(5). Cells cultured in the medium containing 3 × 10(-7) M niobium ions showed the highest ALP activity in comparison with other Nb-containing media or normal medium, regardless of the presence of osteogenic factors (ascorbic acid, β-glycerophosphate and dexamethasone) in the media. Calcium deposition by the cells cultured in the medium containing 3 × 10(-7) M niobium ions was twice as high as those cultured in medium containing no niobium ions. The effects of niobium ions were thought to depend on ion concentration, and to enhance differentiation and mineralization of osteogenic cells rather than their initial adhesion or proliferation.

Trace amounts of ionic calcium and silicon species have been reported to stimulate the proliferation, differentiation, and mineralization of bone-forming cells. Composite materials comprising siloxane-doped calcium carbonate (vaterite) particles and poly(L-lactic acid) have been developed [siloxane-poly(lactic acid)-vaterite hybrid-composite, SiPVH] so far; they were designed such that calcium and silicate ions are gradually released from SiPVH and they show the chronic effects of ions on cellular activities. In the present work, SiPVH with a 3D cotton-like structure was prepared by electrospinning to obtain the major advantages of excellent bioactivity and ease of handling for bone filling surgery. The diameter of the fibrous skeletons that form structure of the cotton-like SiPVH was controlled to ~10 μm to achieve cellular migration into the spaces between fibers. The resulting cotton-like SiPVH showed good flexibility. The fiber surface was coated rapidly with numerous particles of several hundred nanometers in size by alternate soaking in CaCl(2) and Na(2)HPO(4). The treated cotton-like material, which released calcium and silicate ions gradually, showed good cellular migration behavior into the 3D structure in cell culture tests using murine osteoblast-like MC3T3-E1 cells.

Optical topography (OT) based on near-infrared spectroscopy is a noninvasive technique for mapping the relative concentration changes in oxygenated and deoxygenated hemoglobin (oxy- and deoxy-Hb, respectively) in the human cerebral cortex. In our previous study, we developed a small and light wearable optical topography (WOT) system that covers the entire forehead for monitoring prefrontal activation. In the present study, we examine whether the WOT system is applicable to OT measurement while walking, which has been difficult with conventional OT systems. We conduct OT measurements while subjects perform an attention-demanding (AD) task of balancing a ping-pong ball on a small card while walking. The measured time course and power spectra of the relative concentration changes in oxy- and deoxy-Hb show that the step-related changes in the oxy- and deoxy-Hb signals are negligible compared to the task-related changes. Statistical assessment of the task-related changes in the oxy-Hb signals show that the dorsolateral prefrontal cortex and rostral prefrontal area are significantly activated during the AD task. These results suggest that our functional imaging technique with the WOT system is applicable to OT measurement while walking, and will be a powerful tool for evaluating brain activation in a natural environment.

Silicon-releasable microfiber meshes consisting of silicon-doped vaterite (SiV) particles and poly(lactic acid) (PLA) hybrids were prepared by electrospinning. Due to their flexibility and porosity they formed ideal membranes or scaffolds for guided bone regeneration. In addition, a trace amount of silicon species has been reported to stimulate osteogenic cells to mineralize and enhance bone formation. We propose a new method of preparation of silicon-releasing microfiber meshes by electrospinning. Their structure and hydroxyapatite (HA)-forming abilities in simulated body fluid were examined. In addition, we studied their stimulatory effects on osteoblast-like cells in vitro and bone-forming ability in vivo, with a special emphasis on their ability to release silicon. The meshes consisted of a hybrid of carboxy groups in PLA and amino groups in siloxane, derived from aminopropyltriethoxysilane or calcium ions on the SiV surface. This hybrid exhibited an enhanced ability to form HA. The meshes coated with HA released 0.2-0.7 mg l(-1) silicon species into the culture medium over 7 days. Enhanced proliferation of osteoblast-like cells was observed using the meshes and new bone formed on the meshes when implanted into the calvaria of rabbits. These meshes, therefore, provide an excellent substrate for bone regeneration and exhibit enhanced bone-forming ability under both in vitro and in vivo conditions., (Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Cellular activities of human osteoblasts (HOBs) and mesenchymal stem cells (MSCs) on a silicon-releasable scaffold, siloxane-doped poly(lactic acid) and vaterite composite coated with hydroxycarbonate apatite (SPV-H), were estimated using a medium with or without organic factors, such as dexamethasone (Dex) and beta-glycerophosphate (beta-GP), for inducing mineralization or differentiation. As a control, a composite film containing no silicon (denoted by PV-H) was prepared using poly(lactic acid) and vaterite. HOBs cultured on SPV-H formed some agglomerates, bone nodules, after a 21-day culture in a medium without the organic factors, whereas no agglomerate was observed on PV-H. Laser Raman spectra implied that calcium phosphate precipitated in HOBs on the SPV-H. The silicon species in SPV-H stimulated HOBs to mineralization. The culture tests using MSCs show that the level of alkaline phosphatase (ALP) activity in the cells cultured on SPV-H increased during the 21-day culture in a medium without Dex and beta-GP. The level was unchanged in MSCs cultured on PV-H. In the case of supplementing Dex and beta-GP to the medium, the level of ALP activity in MSCs cultured on SPV-H was higher than that on PV-H at all time points during the 21-day culture. The silicon species in SPV-H were regarded to induce and enhance the osteogenic differentiation of MSCs.

A poly(lactic acid) (PLA)/siloxane/calcium carbonate composite membrane containing mercapto groups (PSC-SH) with antibacterial ability and excellent bone-forming ability was prepared using 3-mercaptopropyltrimethoxysilane for application in guided bone regeneration. Mercapto groups were reported to adsorb silver ions, which are well known to show antibacterial activity. Ionic silicon species were reported to stimulate the proliferation of osteoblasts. A PSC-SH membrane with a thickness of about 10 microm shows high flexibility. The PLA in PSC-SH was converted from the crystalline phase to the amorphous phase due to dispersion of condensed siloxane clusters. The amount of mercapto group on PSC-SH surface was estimated to be about 55 nmol mm(-2) by quantitative analysis using the thiol-disulfide exchange reaction. PSC-SH adsorbed silver ions on its surface after being soaked in 6 microM silver acetate aqueous solution for 1 min. The adsorbed silver ions were seen by X-ray photoelectron spectroscopy to form SAg and SO3Ag bonds. A trace amount of ionic silicon species was released from the membrane after soaking in culture medium. PSC-SH with adsorbed silver ions showed good antibacterial activity and cellular compatibility in tests conducted with Staphylococcus aureus and mouse osteoblast-like cells, respectively. Antibacterial activity is expected to occur during the implantation operation by the silver ions but not to remain in the body for a long period, as the ions were present on the surface of the membrane but not inside the structure. The membrane should be useful as a biodegradable material with antibacterial activity and bone-forming ability.

A biodegradable composite with silicon-species releasability was prepared using poly(l-lactic acid) (PLLA) and silicon-doped vaterite (SiV) particles. SiV with particle diameters of approximately 1 mum was prepared using aminopropyltriethoxysilane (APTES) as the silicon species by a carbonation process and then mixed with PLLA in methylene chloride according to a SiV to PLLA weight ratio of 1:2, resulting in the preparation of composite slurry. A composite film was prepared by dipping a cover glass in the slurry. The composite films were incubated in a culture medium for 7 days and the silicon concentration of the medium was measured to estimate the species releasability of the composites. A trace amount of silicon species was continuously released from the composites for 7 days, the amount depending on the content of APTES in SiV. On the composite releasing silicon species, mouse osteoblast-like cells (MC3T3-E1 cells) were significantly stimulated to proliferate and differentiate in comparison with those on a composite containing no silicon species. The proliferation of the cells on the composites releasing larger amounts of silicon species (0.51mgl(-1)day(-1)) was higher than that on the composites releasing smaller amount of the species (0.21mgl(-1)day(-1)). The silicon species in the composites were effective in enhancing the cellular functions. The composites were expected to be useful as a scaffold material for bone tissue engineering.