OBJECTIVES:To investigate how different combinations of base monomers, including diurethane dimethacrylate (DUDMA) and bisphenol A-glycidyl methacrylate (Bis-GMA), and diluent monomers, including trimethylolpropane trimethacrylate (TMPTMA) and triethylene glycol dimethacrylate (TEGDMA), as well as their mixing ratios, influence light attenuation behavior, degree of conversion (DC), mechanical properties, and cell viability in dental resins fabricated by layer-wise additive manufacturing. METHODS:Binary systems were formulated at 5:5 and 7:3 wt ratios. Their optical behavior was characterized using Jacob's working curve, while the degree of conversion (DC) was quantified via ATR-FTIR. Mechanical properties and biocompatibility were evaluated using three-point bending tests, Vickers hardness and CCK-8 assays with human gingival fibroblasts, respectively. RESULTS:All formulations exhibited linear working curve behavior. TEGDMA-containing systems showed significantly higher DC and flexural strength, whereas TMPTMA-containing systems demonstrated greater flexural modulus and Vickers hardness. Mixing ratio effects were system-dependent, with no direct correlation between curing behavior, DC, or mechanical properties. All formulations showed no cytotoxicity in human gingival fibroblasts. SIGNIFICANCE:This study provides a comprehensive understanding of how the interplay between base monomers (DUDMA, Bis-GMA) and diluents (TMPTMA, TEGDMA) dictates the performance of 3D-printed unfilled dental resins. By integrating Jacob's working curve analysis with mechanical and biological evaluations, we identified optimal formulations that balance high degree of conversion with clinical-level biocompatibility. These findings offer a precise chemical roadmap for developing next-generation additive manufacturing resins with tailored mechanical properties for restorative dentistry.

This study aimed to fabricate hybrid blocks by infiltrating various resin compositions into pre-sintered porous lithium disilicate (Li₂Si₂O₅) scaffolds and to evaluate their surface characteristics, mechanical properties, and cytocompatibility. Hybrid ceramic–polymer blocks were produced using mixtures of Bis-GMA, UDMA, and TEGDMA monomers, polymerized at 300 MPa and 180 °C. Four groups (BT82, BT55, UT55, UT73) with different monomer ratios were tested. Complete resin infiltration was achieved in all groups. Surface roughness, contact angle, and water sorption showed no significant differences. However, mechanical properties varied depending on resin composition. UDMA-containing groups (UT55, UT73) exhibited higher flexural strength and Vickers hardness, while Bis-GMA-containing groups showed lower values. Flexural strength was maintained after thermal cycling, but hardness decreased in all groups. All formulations demonstrated excellent cytocompatibility. These results demonstrate that optimizing the resin composition enables the fabrication of lithium disilicate-based hybrid blocks with excellent mechanical properties and biocompatibility, suggesting their potential application as chairside Computer Aided Design/Computer Aided Manufacturing dental restorative materials.

PURPOSE:This study evaluated the cytotoxicity of clinically available dental cements containing resin: conventional adhesive resin cement (ARC), self-adhesive resin cement (SARC), and resin-modified glass-ionomer cement (RMGIC), focusing on their degree of conversion (DC) and effects on cellular responses. METHODS:The DC of all the groups was measured over two weeks under light-free conditions. Cell viability, morphology, and apoptosis were assessed in gingival fibroblasts, dental pulp stem cells, and macrophage cells after exposure to extracts from specimens with different DC values. Eluate analysis was performed using attenuated total reflectance-Fourier transform spectroscopy and gas chromatography/mass spectrometry. RESULTS:The DC increased rapidly within 20 min for ARC and SARC, reaching a plateau at 24 h, while RMGIC showed a slower increase. ARC and SARC exhibited significant cytotoxicity at lower DC levels, with improved cell viability as DC increased. RMGIC displayed minimal cytotoxicity across all DC levels. Analysis revealed unreacted monomers and other substances contributing to cytotoxicity, with apoptotic effects correlating to their concentration in the eluates. CONCLUSIONS:DC significantly influences the cytotoxicity of resin-containing dental cements, with ARC and SARC showing higher cytotoxic effects at lower DC levels compared with RMGIC. Considering DC levels may guide clinicians in minimizing adverse effects when selecting these cements. Dental cements containing resin can release substances that may affect cell viability.

Although self-adhesive resin cements are convenient and less technique-sensitive materials for dental clinicians, they exhibit a lower degree of conversion due to acidic components in their composition. Supplementation of the initiator, accelerator, and activator in self-adhesive resin cements has been suggested to compensate for the lower degree of conversion. This study aimed to evaluate the effects of different combinations of self-curing initiators, self-curing activators, and accelerators on the degree of conversion (DC) of self-adhesive resin cements. A dual-cured self-adhesive resin was prepared using six combinations of initiators, activators, and accelerators. The change in the DC over time was evaluated with and without light curing. The film thickness, flow properties, and cytotoxicity of each formulation were assessed. The results showed that all supplemental components had an effect on increasing the DC, but a greater increase in the DC was observed in the following order: activator, accelerator, and initiator. The cytotoxicity of the resin cements was related to the DC values, as resin cements with lower DC values exhibited higher cytotoxicity. The film thickness met the ISO standards for all groups. The results suggest that utilizing an activator is the most effective approach to enhance the DC in self-adhesive resin cement and that cytotoxicity tended to increase with lower DC values, whereas film thickness and flow properties demonstrated no correlation with DC values.

Spatiotemporal control of exogenous growth factors plays a crucial role in the sequential repair of damaged tissues. However, traditional therapeutic trials have mostly relied on the delivery of a single molecule because of the limitations of rapid diffusion and the instability of biomolecules. In this study, we developed a novel strategy using a composite of gelatin and silica as an alternative for the stable and sequential release of biomolecules. Two biomolecules, basic fibroblast growth factor and bone morphogenetic protein-2, were incorporated into two separate composites and sequentially layered onto the activated polymer surface. Each molecule was sequentially released from each layer of the scaffold and the silica composite prevented rapid diffusion owing to its nano-porous structure. The adhesion, proliferation, and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells were significantly enhanced in the double-layered group containing separately delivered dual molecules compared with the control or single groups. Our developed gelatin–silica composite was successfully placed in double layers on polymer scaffolds, and cellular responses were promoted in this manner. These results demonstrated that our scaffolding system has potential as a therapeutic strategy for the delivery of dual or multiple biomolecules in regenerative medicine.

Spatiotemporal control of exogenous growth factors plays a crucial role in the sequential repair of damaged tissues. However, traditional therapeutic trials have mostly relied on the delivery of a single molecule due to limitations in rapid diffusion and the instability of biomolecules. In this study, we developed a novel strategy using a composite of gelatin and silica as an alternative for the stable and sequential release of biomolecules. Two biomolecules, basic fibroblast growth factor, and bone morphogenetic protein-2, were incorporated into two separate composites and sequentially layered onto the activated polymer surface. Each molecule was sequentially released from each layer of the scaffold, and the silica composite prevented rapid diffusion due to its nanoporous structure. The adhesion, proliferation, and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells were significantly enhanced in the double-layered group containing separately delivered dual molecules compared with the control or single groups. Our developed gelatin-silica composite was successfully incorporated in double layers on polymer scaffolds, and cellular responses were promoted in this manner. These results demonstrated that our scaffolding system has potential as a therapeutic strategy for the delivery of dual or multiple biomolecules in regenerative medicine.

Multivitamin tablet certified reference material (CRM, 108-10-019) was developed for the analysis of seven water-soluble vitamins, including thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxine, biotin, and folic acid. The CRM was prepared in powder form by grinding multivitamin tablets and then mixing, sieving, and bottling the powder. For the certification of each water-soluble vitamin, the isotope dilution mass spectrometry based on the liquid chromatography was applied. The methods for each analyte were validated by confirming the repeatability and reproducibility and by comparing with other CRMs. The property values and uncertainties for the vitamins were determined with 10 units from sample stored at − 20 °C. The homogeneity of each certified component was also examined in the range of 0.48–2.2%. All certified values for the seven water-soluble vitamins were stable for 3 or 6 years after the initial certification under storage conditions at − 20 °C. For fat-soluble vitamins, including retinol, α-tocopherol, cholecalciferol, and phylloquinone, two expert laboratories participated in analyses based on official methods, and the mean values of the reported results were assigned as reference values. The multivitamin tablet CRM (108-10-019) will be useful for validating analytical methods and for ensuring the quality of results for vitamin analysis in multivitamin tablets or similar products.

Statement of problem. Microleakage and loss of the composite resin sealing the screw-access channel are frequent complications of screw-retained implant-supported prostheses. How the screw-access channel should be best restored to reduce such complications is unclear. Purpose. The purpose of this in vitro study was to evaluate the microleakage and bond strength of 3 types of composite resins (flowable, packable, and bulk-fill) with or without a bonding agent treatment to seal the screw-access channel of 2 types of restorative materials (zirconia and Co-Cr alloy) with or without thermocycling. Material and methods. In total, 240 yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) specimens (IPS e.max ZirCAD) and 240 Co-Cr alloy (Vera PDS) specimens were prepared with a empty set3x3-mm cylindrical cavity at the center to simulate the screw-access channel. Three types of composite resins (flowable, packable, and bulk-fill resin) (Filtek Z350 XT Flowable Restorative, Filtek Z350 XT Universal Restorative, and Filtek One Bulk Fill Restorative) were applied to restore the access channel of the zirconia and Co-Cr specimens with or without a bonding agent (Single Bond Universal Adhesive). Microleakage and push-out bond strength were determined and compared by dividing the specimens into experimental groups with or without thermocycling (1000 times with 30 seconds at 5 +/- 2 degrees C and 55 +/- 2 degrees C). The results were analyzed by using a 1-way ANOVA and 4-way ANOVA. Adjustment for multiple comparisons was made with the Tukey Honestly Significant Difference (HSD) test. Results. The specimens subjected to thermocycling showed a lower bond strength (P<.001) and higher microleakage (P<.001) than specimens stored in a constant-temperature water bath. Specimens treated with bonding agents showed a higher bond strength (P<.001) and lower microleakage (P<.001) than specimens not treated with a bonding agent. Higher bond strengths were observed in the order of bulk-fill resin, packable resin, and flowable resin (P<.001). Packable resin showed higher microleakage than flowable resin and bulk-fill resin (P<.05). No significant difference in microleakage was found between the flowable resin and bulk-fill resin (P>.05). Conclusions. Higher bond strengths were observed in the order of bulk-fill resin, packable resin, and flowable resin. Less microleakage was observed in the flowable resin and bulk-fill resin than in the packable composite resin. Bonding agent treatment was effective in increasing bond strength and decreasing microleakage. Zirconia and Co-Cr showed a bond strength similar to that of composite resins, but zirconia showed higher microleakage than Co-Cr. Restoring the screw-access channel with the bulk-fill resin should increase bond strength and reduce microleakage.

Wearable electronic devices that can monitor physiological signals of the human body to provide biomedical information have been drawing extensive interests for sustainable personal health management. Here, we report a human pilot trial of a soft, smart contact lens and a skin-attachable therapeutic device for wireless monitoring and therapy of chronic ocular surface inflammation (OSI). As a diagnostic device, this smart contact lens enables real-time measurement of the concentration of matrix metalloproteinase-9, a biomarker for OSI, in tears using a graphene field-effect transistor. As a therapeutic device, we also fabricated a stretchable and transparent heat patch attachable on the human eyelid conformably. Both diagnostic and therapeutic devices can be incorporated using a smartphone for their wireless communications, thereby achieving instantaneous diagnosis of OSI and automated hyperthermia treatments. Furthermore, in vivo tests using live animals and human subjects confirm their good biocompatibility and reliability as a noninvasive, mobile health care solution.

Abstract An analytical method for the accurate determination of essential fatty acids in cereals and green vegetables is established based on isotope dilution-gas chromatography/mass spectrometry (ID-GC/MS). In this approach, 13C-labeled fatty acids were added as internal standards to the samples prior to the sample preparation. Repeatability and reproducibility for the analyses of the essential fatty acids extracted from homogenized cereals and green vegetables were examined to validate the ID-GC/MS method. The repeatability and reproducibility were within 2% relative standard deviation. The developed method provides higher-order measurement results with the relative expanded uncertainties of 1–2% and 2–4% for cereals and green vegetables, respectively. Based on the fatty acid measurements, the developed ID-GC/MS method can be used as a candidate reference method for the quantitation of essential fatty acids in cereals and green vegetables. The developed method was also applied to analyze several commercially available products including cereal and vegetable powders.

Despite various approaches to immunoassay and chromatography for monitoring cortisol concentrations, conventional methods require bulky external equipment, which limits their use as mobile health care systems. Here, we describe a human pilot trial of a soft, smart contact lens for real-time detection of the cortisol concentration in tears using a smartphone. A cortisol sensor formed using a graphene field-effect transistor can measure cortisol concentration with a detection limit of 10 pg/ml, which is low enough to detect the cortisol concentration in human tears. In addition, this soft contact lens only requires the integration of this cortisol sensor with transparent antennas and wireless communication circuits to make a smartphone the only device needed to operate the lens remotely without obstructing the wearer's view. Furthermore, in vivo tests using live rabbits and the human pilot experiment confirmed the good biocompatibility and reliability of this lens as a noninvasive, mobile health care solution.

Nucleotides play important roles in numerous intracellular biochemical processes and are used in infant formulas and other dairy products. However, domestic analytical methods for assessing nucleotide content in products have not yet been established, and therefore, methods for determining nucleotide content are urgently required. A rapid and simple analytical method for determining the content of five types of nucleotides in dairy products was improved using solid phase extraction clean-up and high-performance liquid chromatography with diode array detector. The extraction solvent used in the AOAC method was not well dissolved and was changed to hydrophilic EDTA-Na. In addition, the results obtained using the isocratic elution method and a single wavelength were similar to those obtained using the AOAC method, and the time taken for analysis was shortened from 40 min to 25 min. The process of method validation revealed the following parameters: accuracy (84.69%-102.72%), precision (1.51%-6.82%), linearity (0.999), and limit of detection (cytidine 5'-monophosphate, 0.09 mg/L; uridine 5'-monophosphate, 0.11 mg/L; adenosine 5'-monophosphate, 0.12 mg/L; guanosine 5'-monophosphate, 0.11 mg/L; and inosine 5'-monophosphate, 0.14 mg/L). The method was also used to determine the nucleotide concentration in 25 samples (infant formulas, 1.99-29.39 mg/100 g; and cow milk, 0.28-0.83 mg/100 g). The newly improved method was appropriate for analyzing nucleotides in infant formulas and other dairy products faster when compared to conventional methods.

Tactile pressure sensors as flexible bioelectronic devices have been regarded as the key component for recently emerging applications in electronic skins, health-monitoring devices, or human-machine interfaces. However, their narrow range of sensible pressure and their difficulty in forming high integrations represent major limitations for various potential applications. Herein, we report fully integrated, active-matrix arrays of pressure-sensitive MoS2 transistors with mechanoluminescent layers and air dielectrics for wide detectable range from footsteps to cellular motions. The inclusion of mechanoluminescent materials as well as air spaces can increase the sensitivity significantly over entire pressure regimes. In addition, the high integration capability of these active-matrix sensory circuitries can enhance their spatial resolution to the level sufficient to analyze the pressure distribution in a single cardiomyocyte. We envision that these wide-range pressure sensors will provide a new strategy toward next-generation electronics at biomachine interfaces to monitor various mechanical and biological phenomena at single-cell resolution.

Injection laryngoplasty is a widely used therapeutic option for drug delivery into vocal folds (VFs). Efficient injectable materials are urgently needed for treating intractable VF disease. Liquid-type non-thermal atmospheric plasma (LTP) has been found to be useful for various biological applications, including in regenerative medicine. We evaluated the effects of LTP on VF regeneration. Migration and matrix metalloproteinase-2 expression of lipopolysaccharide (LPS)-treated human vocal fold-derived mesenchymal stem cells (VF-MSCs) were enhanced by LTP treatment. LTP treatment not only ameliorated nuclear factor-κB and interleukin-6 activation, induced by LPS treatment, but also the increased manifestation of α-smooth muscle actin and fibronectin, induced by transforming growth factor-ß. In a rabbit VF scarring animal model, histological analyses showed increased hyaluronic acid deposition and decreased collagen accumulation after LTP injection. Videokymographic analysis showed more improved vibrations in LTP-treated VF mucosa compared to those in non-treated group. In conclusion, LTP treatment enhanced the recruitment and activation of VF-MSCs. Regulated extracellular matrix (ECM) synthesis and eventual functional improvement of scarred VFs were observed upon LTP treatment. The results of this study suggest that LTP injection can enhance wound healing and improve functional remodeling following VF injury. Impact statement Voice disorder has a significant impact on life quality, and one of the major causes of this voice disorder is vocal fold scarring. Therefore, various approaches have been tried to treat for voice disorder. However, no method has satisfied all requirements until now. Plasma medicine, which involves the medical application of plasma, is a rapidly developing field. We have confirmed that liquid-type plasma improved vocal fold scarring by mobilizing and activating vocal fold fibroblast. In conclusion, liquid-type plasma is a potential therapeutic agent for promoting vocal fold scarring through simple injection and it may be an alternative therapeutic agent for the current situation to treat voice disorder.

Recapitulating the in vivo microenvironments of damaged tissues through modulation of the physicochemical properties of scaffolds can boost endogenous regenerative capacity. A series of critical events in tissue healing including immune-responses, angiogenesis, and stem cell homing and differentiation orchestrate to relay the regeneration process. Herein, we report hierarchically structured (‘microchanneled’) 3D printed scaffolds (named ‘μCh’), in contrast to conventional 3D printed scaffolds, induce such cellular responses in a unique way that contributes to accelerated tissue repair and remodeling. The μCh reduced the extracellular trap formation of anchored neutrophils at the very beginning (24 h) of implantation while increasing the number of live cells. Among the macrophages covered the surface of μCh over 7 days a major population polarized toward alternativelly activated phase (M2) which contrasted with control scaffolds where classically activated phase (M1) being dominant. The mesenchymal stem cells (MSCs) recruited to the μCh were significantly more than those to the control, and the event was correlated with the increased level of stem cell homing cytokine, stromal derived factor 1 (SDF1) sequestered to the μCh. Furthermore, the neo-blood vessel formation was more pronounced in the μCh, which was in line with the piling up of angiogenic factor, vascular endothelial growth factor (VEGF) in the μCh. Further assays on the protein sequestration to the μCh revealed that a set of chemokines involved in early pro-inflammatory responses were less found whereas representative adhesive proteins engaged in the cell-matrix interactions were significantly more captured. Ultimately, the fibrous capsule formation on the μCh was reduced with respect to the control, when assessed for up to 21 days, indicating less severe foreign body reaction. The tissue healing and regenerative capacity of the μCh was then confirmed in a critically sized bone model, where those series of events observed are essential to relay bone regeneration. The results over 6 weeks showed that the μCh significantly enhanced the early bone matrix deposition and accelerated bone regeneration. While more in-depth studies remain as to elucidate the underlying mechanisms for each biological event, the molecular, cellular and tissue reactions to the μCh were coherently favorable for the regeneration process of tissues, supporting the engineered scaffolds as potential therapeutic 3D platforms.

Defects in bone are some of the most difficult injuries to treat. Biomimetic scaffolds represent a promising approach for successful bone tissue regeneration. In this study, a three-dimensional (3D) scaffold with osteo-inductive functionality was designed and assayed both in-vitro and in-vivo. Bone formation peptide-1 (BFP1), an osteo-promoting specific peptide, was covalently bound to a 3D printed polycaprolactone (PCL) scaffold using polydopamine (DOPA). The amount of BFP1 immobilized on the surface was found to increase depending on the BFP1 concentration of the loading solution. To observe the biological effects of the 3D scaffolds, human tonsil-derived mesenchymal stem cells (hTMSCs) were isolated. The cells were cultured on the scaffolds and observed to rapidly differentiate into osteoblast-like cells with osteo-promoting capabilities. The scaffolds were implanted in a rabbit calvarial defect model for 8 weeks and successfully stimulated both vessel and bone regeneration. Osteo-promoting 3D scaffolds may provide a safer and more efficient approach for bone repair and remodelling in regenerative medicine.

Although many graft materials have been used for augmentation rhinoplasty, an ideal graft has not yet been developed. As the field of tissue engineering has been developing, it has been applied to the reconstruction of many organs, but its application in the rhinoplasty field is still limited. This study evaluated the utility of allogenic chondrocytes with fibrin/hyaluronic acid (HA)-poly(l-lactic-co-glycolic acid) (PLGA) constructs in augmentation rhinoplasty. Chondrocytes from rabbit auricular cartilage were isolated and cultured with fibrin/HA hydrogels and implanted into PLGA scaffolds. After 8 weeks of in vitro culture, the scaffolds were implanted in the nasal dorsum of six rabbits. Eight weeks postoperatively, the implanted sites were evaluated with gross, radiologic, and histologic analysis. In vitro, more than 90% of the seeded chondrocytes in the PLGA scaffolds survived for 2 weeks, and they produced a large amount of extracellular matrix and were well differentiated. The grafts maintained their initial shape for 8 weeks after implantation. Radiological and histological evaluations showed that the structure was well maintained with minimal inflammatory response and appropriate elevation levels. However, the formation of neo-chondrocytes was not observed. PLGA scaffolds seeded with fibrin/HA and allogenic chondrocytes can be a biocompatible augmentation material in rhinoplasty in the future.

Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctional and structurally-stable biomatrices. The hybrid protein, integrated homogeneously with collagen fibrillar networks, preserved structural stability over a month. Biological efficacy of the hybrid matrix was proven onto tethered surface of biopolymer porous scaffolds. Mesenchymal stem cells quickly anchored to the hybrid matrix, forming focal adhesions, and substantially conformed to cytoskeletal extensions, benefited from the fibronectin adhesive domains. Cells achieved high proliferative capacity to reach confluence rapidly and switched to a mature and osteogenic phenotype more effectively, resulting in greater osteogenic matrix syntheses and mineralization, driven by the engineered osteocalcin. The hybrid biomimetic matrix significantly improved in vivo bone formation in calvarial defects over 6 weeks. Based on the series of stimulated biological responses in vitro and in vivo the novel hybrid proteinaceous composition will be potentially useful as stem cell interfacing matrices for osteogenesis and bone regeneration.

Over the past few years, attention has been focused on the therapeutic roles in designing bone scaffolds for successful repair and regeneration. Indeed, biologically dynamic events in the bone healing process involve many of the molecules and cells adherent to the scaffold. Recent bone scaffolds have been designed considering intrinsic chemical and physical factors and exogenous/extrinsic cues that induce bone regeneration. Here, we attempt to topically review the current trends and to suggest featured strategies for the design of therapeutically relevant bone scaffolds taking into account recent studies and applications.