RESUMEN

Oral conditions, such as recurrent aphthous stomatitis, are chronic inflammatory disorders that significantly affect the life quality. This study aims to develop a novel buccal mucoadhesive based on methacrylate hydroxypropyl methylcellulose (M-HPMC) and methacrylate lignin (M-SLS) encapsulated with nanostructured lipid carriers (NLCs) for controlled release of alpha-pinene (α-pinene). NLCs with particle sizes of 152 ± 3 nm were prepared by using stearic acid and oleic acid as solid and liquid lipids, respectively. Following the successful synthesis of M-HPMC and M-SLS, various concentrations of α-pinene loaded NLCs (0, 18, 38, and 50 wt%) were encapsulated in M-HPMC/M-SLS hydrogel. It was demonstrated that the physiological and mechanical performances of hydrogels were changed, depending on the NLC content. Remarkably, the incorporation of 18 wt% NLC improved the compressive strength (143 ± 14 kPa) and toughness (17 ± 1 kJ/m3) of M-HPMC/M-SLS hydrogel. This nanocomposite hydrogel considerably decreased dissipated energy from 1.64 kJ/m3 to 0.99 kJ/m3, after a five-cycle compression test. The nanocomposite hydrogel exhibited controlled α-pinene release for up to 96 h which could significantly improve the antioxidant activity of M-HPMC/M-SLS matrix. Moreover, the reinforcing M-HPMC/M-SLS hydrogel with α-pinene-loaded NLCs resulted in increased adhesive strength (113.5 ± 7.5 kPa) to bovine buccal mucosa and cytocompatibility in contact with fibroblasts.

Asunto(s)

Monoterpenos Bicíclicos , Hidrogeles , Derivados de la Hipromelosa , Lignina , Nanocompuestos , Lignina/química , Monoterpenos Bicíclicos/química , Monoterpenos Bicíclicos/farmacología , Hidrogeles/química , Hidrogeles/síntesis química , Hidrogeles/farmacología , Nanocompuestos/química , Animales , Derivados de la Hipromelosa/química , Ratones , Metacrilatos/química , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/síntesis química , Antioxidantes/administración & dosificación , Fibroblastos/efectos de los fármacos

RESUMEN

Microcarriers for large-scale cell culture have a broader prospect in cell screening compared with the traditional high cost, low efficiency, and cell damaging methods. However, the equal biological affinity to cells has hindered its application. Therefore, based on the antifouling strategy of zwitterionic polymer, we developed a cell-specific microcarrier (CSMC) for shielding non-target cells and capturing mesenchymal stem cells (MSCs), which has characteristics of high biocompatibility, low background noise and high precision. Briefly, [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide and glycidyl methacrylate were grafted onto polygalacturonic acid, respectively. The former built a hydration layer through solvation to provide an excellent antifouling surface, while the latter provided active sites for the click reaction with sulfhydryl-modified cell-specific peptides, resulting in rapid immobilization of peptides. This method is applicable to the vast majority of polysaccharide materials. The accurate capture ratio of MSCs by CSMC in a mixed multicellular environment is >95 % and the proliferation rate of MSCs on microcarriers is satisfactory. In summary, this grafting strategy of bioactive components lays a foundation for the application of polysaccharide materials in the biomedical field, and the specific adhesive microcarriers also open up new ideas for the development of stem cell screening as well.

Asunto(s)

Células Madre Mesenquimatosas , Pectinas , Péptidos , Células Madre Mesenquimatosas/citología , Pectinas/química , Péptidos/química , Metacrilatos/química , Proliferación Celular/efectos de los fármacos , Compuestos Epoxi/química , Humanos , Animales , Materiales Biocompatibles/química

RESUMEN

Reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization-induced self-assembly (PISA) was conducted in the presence of poly(methyl methacrylate) (PMMA) stabilizer in ethanol/water mixture (80/20 by volume). Two different systems were explored by utilizing (i) 2-ethylhexyl methacrylate (EHMA) and (ii) n-butyl methacrylate (BMA). The morphology transitions of these systems were investigated by varying the polymerization conditions, i.e., the presence of the solvophilic comonomer MMA, the solids content, and the target degree of polymerization (DP). As observed in conventional PISA, the presence of solvophilic comonomer, increase in solids content and target DP promoted the formation of high-order morphology. However, unusual morphology transitions were observed whereby the morphology transformed from high-order morphologies to a mixture of spherical nanoparticles, worms, and vesicles and finally to vesicles with increasing target DP. This unusual evolution may be attributed to the limited solubility of PMMA in the ethanol/water solvent mixture, whereby PMMA is soluble at the polymerization temperature but insoluble at lower temperatures.

Asunto(s)

Polimerizacion , Polimetil Metacrilato , Agua , Polimetil Metacrilato/química , Agua/química , Metacrilatos/química , Etanol/química

RESUMEN

Alveolar bone defect reconstruction is a common challenge in stomatology. To address this, a thermosensitive/photosensitive gelatin methacrylate (GelMA) gel was developed based on various air solubilities and light-curing technologies. The gel was synthesized by using a freeze-ultraviolet (FUV) method to form a porous and quickly (within 15 min) solidifying modified network structure. Unlike other gel scaffolds limited by complex preparation procedures and residual products, this FUV-GelMA gel shows favorable manufacturing ability, promising biocompatibility, and adjustable macroporous structures. The results from a rat model suggested that this gel scaffold creates a conducive microenvironment for mandible reconstruction and vascularization. In vitro experiments further confirmed that the FUV-GelMA gel promotes osteogenic differentiation of human bone marrow mesenchymal stem cells and angiogenesis of human umbilical vein endothelial cells. Investigation of the underlying mechanism focused on the p38 mitogen-activated protein kinase (MAPK) pathway. We found that SB203580, a specific inhibitor of p38 MAPK, abolished the therapeutic effects of the FUV-GelMA gel on osteogenesis and angiogenesis, both in vitro and in vivo. These findings introduced a novel approach for scaffold-based tissue regeneration in future clinical applications.

Asunto(s)

Gelatina , Células Endoteliales de la Vena Umbilical Humana , Células Madre Mesenquimatosas , Metacrilatos , Neovascularización Fisiológica , Osteogénesis , Andamios del Tejido , Rayos Ultravioleta , Gelatina/química , Gelatina/farmacología , Osteogénesis/efectos de los fármacos , Humanos , Animales , Metacrilatos/química , Metacrilatos/farmacología , Porosidad , Neovascularización Fisiológica/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Andamios del Tejido/química , Ratas , Ratas Sprague-Dawley , Ingeniería de Tejidos/métodos , Diferenciación Celular/efectos de los fármacos , Congelación , Masculino , Geles/química , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Angiogénesis

RESUMEN

The viscosity of gelatin methacryloyl (GelMA)-based bioinks generates shear stresses throughout the printing process that can affect cell integrity, reduce cell viability, cause morphological changes, and alter cell functionality. This study systematically investigated the impact of the viscosity of GelMA-gelatin bioinks on osteoblast-like cells in 2D and 3D culture conditions. Three bioinks with low, medium, and high viscosity prepared by supplementing a 5% GelMA solution with different concentrations of gelatin were evaluated. Cell responses were studied in a 2D environment after printing and incubation in non-cross-linked bioinks that caused the gelatin and GelMA to dissolve and release cells for attachment to tissue culture plates. The increased viscosity of the bioinks significantly affected cell area and aspect ratio. Cells printed using the bioink with medium viscosity exhibited greater metabolic activity and proliferation rate than those printed using the high viscosity bioink and even the unprinted control cells. Additionally, cells printed using the bioink with high viscosity demonstrated notably elevated expression levels of alkaline phosphatase and bone morphogenetic protein-2 genes. In the 3D condition, the printed cell-laden hydrogels were photo-cross-linked prior to incubation. The medium viscosity bioink supported greater cell proliferation compared to the high viscosity bioink. However, there were no significant differences in the expression of osteogenic markers between the medium and high viscosity bioinks. Therefore, the choice between medium and high viscosity bioinks should be based on the desired outcomes and objectives of the bone tissue engineering application. Furthermore, the bioprinting procedure with the medium viscosity bioink was used as an automated technique for efficiently seeding cells onto 3D printed porous titanium scaffolds for bone tissue engineering purposes.

Asunto(s)

Bioimpresión , Gelatina , Tinta , Metacrilatos , Gelatina/química , Viscosidad , Metacrilatos/química , Bioimpresión/métodos , Impresión Tridimensional , Osteoblastos/citología , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ingeniería de Tejidos , Línea Celular , Animales , Andamios del Tejido/química , Humanos , Supervivencia Celular/efectos de los fármacos , Huesos/citología

RESUMEN

To control three-dimensional (3D) cell spheroid formation, it is well-known the surface physicochemical and mechanical properties of cell culture materials are important; however, the formation and function of 3D cells are still unclear. This study demonstrated the precise control of the formation of 3D cells and 3D cell functions using diblock copolymers containing different ratios of a zwitterionic trimethylamine N-oxide group. The diblock copolymers were composed of poly(n-butyl methacrylate) (PBMA) as the hydrophobic unit for surface coating on a cell culture dish and stabilization in water, and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) as the precursor of N-oxide. The zwitterionic N-oxide converted from 0 to 100% using PDMAEMA. The wettability and surface zeta potential varied with different ratios of N-oxide diblock copolymer-coated surfaces, and the amount of protein adsorbed in the cell culture medium decreased monotonically with increasing N-oxide ratio. 3D cell spheroid formations were observed by seeding human umbilical cord mesenchymal stem cells (hUC-MSCs) in diblock copolymer-coated flat-bottom well plates, and the N-oxide ratio was over 40%. The cells proliferated in two-dimensions (2D) and did not form spheroids when the N-oxide ratio was less than 20%. Interestingly, the expression of undifferentiated markers of hUC-MSCs was higher on surfaces that adsorbed proteins to some extent and formed 50-150 µm spheroids in the range of 40-70% of N-oxide ratio. We revealed that a moderately protein-adsorbed surface allows precise control of spheroid formation and undifferentiated 3D cells and has potential applications for high-quality spheroids in regenerative medicine and drug screening.

Asunto(s)

Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Metacrilatos/química , Esferoides Celulares/citología , Esferoides Celulares/metabolismo , Polímeros/química , Propiedades de Superficie , Nylons/química , Técnicas de Cultivo Tridimensional de Células , Células Cultivadas , Óxidos/química , Proliferación Celular/efectos de los fármacos

RESUMEN

OBJECTIVES: To investigate the effect of neutral 10-methacryloyloxydecyl dihydrogen phosphate salt (MDP-Na) on the dentin bond strength and remineralization potential of etch-&-rinse adhesive. METHODS: Two experimental etch-&-rinse adhesives were formulated by incorporating 0 wt% (E0) or 20 wt% (E20) neutral MDP-Na into a basic primer. A commercial adhesive, Adper Single Bond 2 (SB, 3 M ESPE), served as the control. Sixty prepared teeth were randomly allocated into three groups (n = 20) and bonded using either one of the experimental adhesives or SB. Following 24 h of water storage, the bonded specimens were sectioned into resin-dentin sticks, with four resin-dentin sticks obtained from each tooth for microtensile bond strength (MTBS) test. Half of the sticks from each group were immediately subjected to tensile loading using a microtensile tester at a crosshead speed of 1 mm/min, while the other half underwent tensile loading after 6-month incubation in artificial saliva (AS). The degree of conversion (DC) of both the control and experimental adhesives (n = 6 in each group) and the adsorption properties of MDP-Na on the dentin organic matrix (n = 5 in each group) were determined using Fourier-transform infrared spectrometry. Furthermore, the effectiveness of neutral MDP-Na in promoting the mineralization of two-dimensional collagen fibrils and the adhesive-dentin interface was explored using transmission electron microscopy and selected-area electron diffraction. Two- and one-way ANOVA was employed to assess the impact of adhesive type and water storage on dentin bond strength and the DC (α = 0.05). RESULTS: The addition of MDP-Na into the primer increased both the short- and long-term MTBS of the experimental adhesives (p = 0.00). No difference was noted in the DC between the control, E0 and E20 groups (p = 0.366). The MDP-Na remained absorbed on the demineralized dentin even after thorough rinsing. The intra- and extra-fibrillar mineralization of the two-dimensional collagen fibril and dentin bond hybrid layer was confirmed by transmission electron microscopy and selected-area electron diffraction when the primer was added with MDP-Na. CONCLUSIONS: The use of neutral MDP-Na results in high-quality hybrid layer that increase the dentin bond strength of etch-&-rinse adhesive and provides the adhesive with remineralizing capability. This approach may represent a suitable bonding strategy for improving the dentin bond strength and durability of etch-&-rinse adhesive.

Asunto(s)

Recubrimiento Dental Adhesivo , Recubrimientos Dentinarios , Dentina , Metacrilatos , Resistencia a la Tracción , Metacrilatos/química , Humanos , Recubrimiento Dental Adhesivo/métodos , Dentina/ultraestructura , Dentina/efectos de los fármacos , Recubrimientos Dentinarios/química , Remineralización Dental/métodos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Grabado Ácido Dental/métodos , Análisis del Estrés Dental , Técnicas In Vitro , Cementos de Resina/química , Espectroscopía Infrarroja por Transformada de Fourier , Cementos Dentales/química , Propiedades de Superficie

RESUMEN

This study aimed to synthesize a novel elastomeric ligature with dimethylaminohexadecyl methacrylate (DMAHDM) grafted, providing a new strategy for improving the issue of enamel demineralization during fixed orthodontics. DMAHDM was incorporated into elastomeric ligatures at different mass fractions using ultraviolet photochemical grafting. The antibacterial properties were evaluated and the optimal DMAHDM amount was determined based on cytotoxicity assays. Moreover, tests were conducted to evaluate the in vivo changes in the mechanical properties of the elastomeric ligatures. To assess the actual in vivo effectiveness in preventing enamel demineralization, a rat demineralization model was established, with analyses focusing on changes in surface microstructure, elemental composition, and nanomechanical properties. Elastomeric ligatures with 2% DMAHDM showed excellent biocompatibility and the best antibacterial properties, reducing lactic acid production by 65.3% and biofilm bacteria by 50.0% within 24 h, without significant mechanical property differences from the control group (p > 0.05). Most importantly, they effectively prevented enamel demineralization in vivo, enhancing elastic modulus by 73.2% and hardness by 204.8%. Elastomeric ligatures incorporating DMAHDM have shown great potential for application in preventing enamel demineralization, providing a new strategy to solve this issue during fixed orthodontics.

Asunto(s)

Esmalte Dental , Elastómeros , Desmineralización Dental , Desmineralización Dental/prevención & control , Animales , Elastómeros/química , Ratas , Esmalte Dental/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Metacrilatos/química , Metacrilatos/farmacología , Aparatos Ortodóncicos , Biopelículas/efectos de los fármacos , Masculino

RESUMEN

The terpolymers of N-vinylpyrrolidone (VP) with acrylic acid and triethylene glycol methacrylate were synthesized with more than 90% yield by radical copolymerization in ethanol from monomeric mixtures of different molar composition (98:2:2, 95:5: 2 and 98:2:5) and their monomer composition, absolute molecular masses and hydrodynamic radii in aqueous media were determined. Using the MTT test, these terpolymers were established to be low toxic for non-tumor Vero cells and HeLa tumor cells. Polymer compositions of hydrophobic dye methyl pheophorbide a (MPP) based on studied terpolymers and linear polyvinylpyrrolidone (PVP) were obtained and characterized in water solution. Quantum-chemical modeling of the MPP-copolymer structures was conducted, and the possibility of hydrogen bond formation between terpolymer units and the MPP molecule was shown. Using fluorescence microscopy, the accumulation and distribution of polymer particles in non-tumor (FetMSC) and tumor (HeLa) cells was studied, and an increase in the accumulation of MPP with both types of particles was found.

Asunto(s)

Acrilatos , Humanos , Animales , Chlorocebus aethiops , Acrilatos/química , Células Vero , Células HeLa , Sistemas de Liberación de Medicamentos , Pirrolidinonas/química , Metacrilatos/química , Polietilenglicoles/química , Polímeros/química , Polímeros/síntesis química , Supervivencia Celular/efectos de los fármacos

RESUMEN

Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL's therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.

Asunto(s)

Angiogénesis , Plaquetas , Gelatina , Metacrilatos , Úlcera por Presión , Piel , Cicatrización de Heridas , Animales , Humanos , Ratones , Angiogénesis/efectos de los fármacos , Plaquetas/metabolismo , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Gelatina/química , Gelatina/farmacología , Células Endoteliales de la Vena Umbilical Humana , Hidrogeles/química , Metacrilatos/química , Metacrilatos/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Úlcera por Presión/terapia , Regeneración/efectos de los fármacos , Piel/irrigación sanguínea , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Factor de Transcripción STAT3/metabolismo , Cicatrización de Heridas/efectos de los fármacos

RESUMEN

Purpose/Aim: Acrylamides are hydrolytically stable at pH lower than 2, and were shown to preserve bonded interface integrity with two-step, total etch adhesives. The objective of this study was to leverage those two characteristics in self-etching primers containing the acidic monomer 10-MDP and test the microtensile bond strength before and after incubation with S. mutans incubation. Materials and Methods: Acidic primers (10 wt % 10-methacryloyloxydecyl dihydrogen phosphate─10-MDP; 45 wt % N,N-diethyl-1,3-bis(acrylamido)propane─DEBAAP, or 2-hydroxyethyl methacrylate─HEMA; 45 wt %, glycerol-dimethacrylate─GDMA) and adhesives (DEBAAP or HEMA/10-MDP/UDMA 45/10/45 wt %) were made polymerizable by the addition of 0.2 wt % camphorquinone, 0.8 wt % ethyl-4-dimethylaminobenzoate, 0.4 wt % diphenyliodonium hexafluorophosphate, and 0.1 wt % butylhydroxytoluene. Nonsolvated materials were characterized for flexural strength (FS), modulus (E), toughness, water sorption/solubility (WS/SL), contact angle, and vinyl conversion (DC). Viscosity was evaluated after adding 20 and 40 vol % ethanol to the primer and adhesive, respectively. The experimental materials or Clearfil SE Bond (CC─commercial control) were used to bond a commercial composite (Filtek Supreme) to the flat surface of human dentin. Microtensile bond strength (MTBS) was tested in 1 mm2 sticks for the 5 primer/bond combinations: CC (Clearfil Bond Primer and Bond), HH (HEMA/HEMA), DD (DEBAAP/DEBAAP), HD (HEMA/DEBAAP), and DH (DEBAAP/HEMA). Prior to testing, sticks were stored in water or biofilm-inducing culture medium with S. mutans for 1 week. Confocal images and FTIR-ATR evaluation evaluated the hybrid layer of the adhesives. Results were analyzed using Student's t-test (WS, SL, DC, contact angle, FS, E, toughness), one-way ANOVA/Tukey's test for viscosity, and two-way ANOVA/Tukey's test for MTBS (95%). Results: HEMA-based materials had lower contact angle (p = 0.004), higher WS (p < 0.001), and similar SL values compared to DEBAAP (p = 0.126). FS (p = 0.171) and E (p = 0.065) dry values were similar, but after one week of water storage, FS/E dropped more significantly for HEMA materials. Dry and wet toughness was greater for DEBAAP (p < 0.001), but it also had the greatest drop (46%). Clearfil bonds had the highest viscosity, followed by DEBAAP and HEMA, respectively (p = 0.002). For the primers, HEMA had the lowest viscosity (p = 0.003). As far as MTBS, all groups tested in water were statistically different when compared with HH (p < 0.001). After storage in biofilm, DH had the highest MTBS value, being statistically different from HH (p = 0.002), CC (p = 0.015), and DD (p = 0.027). Conclusions: The addition of a diacrylamide and its association with HEMA in self-etching adhesive systems provided greater bonding stability after bacterial challenge.

Asunto(s)

Streptococcus mutans , Streptococcus mutans/efectos de los fármacos , Resistencia a la Tracción , Dentina/química , Dentina/microbiología , Recubrimientos Dentinarios/química , Humanos , Ensayo de Materiales , Metacrilatos/química , Cementos Dentales/química , Cementos de Resina/química

RESUMEN

The current treatments for wounds often fail to induce adequate healing, leaving wounds vulnerable to persistent infections and development of drug-resistant microbial biofilms. New natural-derived nanoparticles were studied to impair bacteria colonization and hinder the formation of biofilms in wounds. The nanoparticles were fabricated through polyelectrolyte complexation of chitosan (CS, polycation) and hyaluronic acid (HA, polyanion). UV-induced photo-crosslinking was used to enhance the stability of the nanoparticles. To achieve this, HA was methacrylated (HAMA, degree of modification of 20 %). Photo-crosslinked nanoparticles obtained from HAMA and CS had a diameter of 478 nm and a more homogeneous size distribution than nanoparticles assembled solely through complexation (742 nm). The nanoparticles were loaded with the antimicrobial agent bacitracin (BC), resulting in nanoparticles with a diameter of 332 nm. The encapsulation of BC was highly efficient (97 %). The BC-loaded nanoparticles showed significant antibacterial activity against gram-positive bacteria Staphylococcus aureus, Methicillin-resistant S. aureus and S. epidermidis. Photo-crosslinked HAMA/CS nanoparticles loaded with BC demonstrated inhibition of biofilm formation and a positive effect on the proliferation of mammalian cells (L929). These crosslinked nanoparticles have potential for the long-term treatment of wounds and controlled antibiotic delivery at the location of a lesion.

Asunto(s)

Antibacterianos , Bacitracina , Biopelículas , Quitosano , Ácido Hialurónico , Nanopartículas , Quitosano/química , Quitosano/farmacología , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Nanopartículas/química , Antibacterianos/farmacología , Antibacterianos/química , Bacitracina/farmacología , Bacitracina/química , Biopelículas/efectos de los fármacos , Portadores de Fármacos/química , Metacrilatos/química , Metacrilatos/farmacología , Animales , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Ratones

RESUMEN

OBJECTIVES: Considering the correlation between survival microenvironment of E. faecalis and acidic pH value, this study aimed to investigate the potential of utilizing pH-responsive DMAEM monomers and their copolymers with resin-based root canal sealers to inhibit E. faecalis. METHODS: Broth microdilution assay, crystal violet staining and qPCR were performed to evaluate antibacterial effects of DMAEM monomers against E. faecalis at different pH. Methacrylate-resin based root canal sealers were prepared and copolymerized with DMAEM. The flow, solubility, water sorption, apical sealing ability and cytotoxicity of sealers were investigated to optimize formulation. The anti-E. faecalis effects of DMAEM copolymers with sealers were evaluated by direct contact test, colony-forming unit counting and live/dead staining. RESULTS: DMAEM monomers inhibited the growth, biofilm formation and virulence factors expression of E. faecalis in a concentration- and pH-dependent manner. Incorporation of 1.25 % and 2.5 % DMAEM into experimental sealers would not affect the flowability, solubility and periapical sealing ability (P > 0.05), but increased the water sorption of sealers (P < 0.01). Cells viability was higher than 90 % in both 1.25 % and 2.5 % DMAEM groups at pH 7.0. DMAEM copolymers with sealers reduced E. faecalis counts, inhibited biofilm formation and decreased live cells within the biofilm in response to pH values. SIGNIFICANCE: DMAEM monomers and their copolymers with resin-based sealers possessed antibacterial and antibiofilm effects on E. faecalis in response to pH values. DMAEM is promising to inhibit intraradicular E. faecalis in response to its acidic survival environment and maintain low cytotoxicity under neutral conditions, ensuring their biosafety in case of inadvertent entry into periapical tissues.

Asunto(s)

Biopelículas , Enterococcus faecalis , Metacrilatos , Materiales de Obturación del Conducto Radicular , Enterococcus faecalis/efectos de los fármacos , Concentración de Iones de Hidrógeno , Metacrilatos/farmacología , Metacrilatos/química , Biopelículas/efectos de los fármacos , Materiales de Obturación del Conducto Radicular/farmacología , Materiales de Obturación del Conducto Radicular/química , Antibacterianos/farmacología , Antibacterianos/química , Ensayo de Materiales , Solubilidad

RESUMEN

OBJECTIVES: To synthesize casein enzymatic hydrolysate (CEH)-laden gelatin methacryloyl (GelMA) fibrous scaffolds and evaluate the cytocompatibility and anti-inflammatory effects on dental pulp stem cells (DPSCs). MATERIALS AND METHODS: GelMA fibrous scaffolds with 10%, 20%, and 30% CEH (w/w) and without CEH (control) were obtained via electrospinning. Chemo-morphological, degradation, and mechanical analyses were conducted to evaluate the morphology and composition of the fibers, mass loss, and mechanical properties, respectively. Adhesion/spreading and viability of DPSCs seeded on the scaffolds were also assessed. The anti-inflammatory potential on DPSCs was tested after the chronic challenge of cells with lipopolysaccharides (LPS), followed by treatment with extracts obtained after immersing the scaffolds in α-MEM. The synthesis of the pro-inflammatory cytokines IL-6, IL-1α, and TNF-α was measured by ELISA. Data were analyzed by ANOVA/post-hoc tests (α = 5%). RESULTS: CEH-laden electrospun fibers had a larger diameter than pure GelMA (p ≤ 0.036). GelMA scaffolds laden with 20% and 30% CEH had a greater mass loss. Tensile strength was reduced for the 10% CEH fibers (p = 0.0052), whereas no difference was observed for the 20% and 30% fibers (p ≥ 0.6736) compared to the control. Young's modulus decreased with CEH (p < 0.0001). Elongation at break increased for the 20% and 30% CEH scaffolds (p ≤ 0.0038). Over time, DPSCs viability increased across all groups, indicating cytocompatibility, with CEH-laden scaffolds exhibiting greater cell viability after seven days (p ≤ 0.0166). Also, 10% CEH-GelMA scaffolds decreased the IL-6, IL-1α, and TNF-α synthesis (p ≤ 0.035). CONCLUSION: CEH-laden GelMA scaffolds facilitated both adhesion and proliferation of DPSCs, and 10% CEH provided anti-inflammatory potential after chronic LPS challenge. CLINICAL RELEVANCE: CEH incorporated in GelMA fibrous scaffolds demonstrated the potential to be used as a cytocompatible and anti-inflammatory biomaterial for vital pulp therapy.

Asunto(s)

Antiinflamatorios , Caseínas , Supervivencia Celular , Pulpa Dental , Gelatina , Andamios del Tejido , Gelatina/química , Pulpa Dental/citología , Pulpa Dental/efectos de los fármacos , Andamios del Tejido/química , Humanos , Antiinflamatorios/farmacología , Supervivencia Celular/efectos de los fármacos , Metacrilatos/química , Ensayo de Materiales , Ensayo de Inmunoadsorción Enzimática , Resistencia a la Tracción , Células Cultivadas , Células Madre/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Citocinas/metabolismo , Propiedades de Superficie

RESUMEN

Multiresponsive hydrogels are valuable as biomaterials due to their ability to respond to multiple biologically relevant stimuli, i.e., temperature, pH, or reactive oxygen species (ROS), which can be present simultaneously in the body. In this work, we synthesize triple-responsive hydrogels through UV light photopolymerization of selected monomer compositions that encompass thermoresponsive N-isopropylacrylamide (NIPAM), pH-responsive methacrylic acid (MAA), and a tailor-made ROS-responsive diacrylate thioether monomer (EG3SA). As a result, smart P[NIPAMx-co-MAAy-co-(EG3SA)z] hydrogels capable of being manufactured by digital light processing (DLP) 4D printing are obtained. The thermo-, pH-, and ROS-response of the hydrogels are studied by swelling tests and rheological measurements at different temperatures (25 and 37 °C), pHs (3, 5, 7.4, and 11), and in the absence or presence of ROS (H2O2). The hydrogels are employed as matrixes for the encapsulation of ketoprofen (KET), an anti-inflammatory drug that shows a tunable release, depending on the hydrogel composition and stimuli applied. The cytotoxicity properties of the hydrogels are tested in vitro with mouse embryonic fibroblasts (NIH 3T3) and RAW 264.7 murine macrophage (RAW) cells. Finally, the anti-inflammatory properties are assessed, and the results exhibit a ≈70% nitric oxide reduction up to base values of pro-inflammatory RAW cells, which highlights the anti-inflammatory capacity of P[NIPAM80-co-MAA15-co-(EG3SA)5] hydrogels, per se, without being necessary to encapsulate an anti-inflammatory drug within their network. It opens the route for the fabrication of customizable 4D printable scaffolds for the effective treatment of inflammatory pathologies.

Asunto(s)

Antiinflamatorios , Hidrogeles , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Animales , Células RAW 264.7 , Antiinflamatorios/farmacología , Antiinflamatorios/química , Cetoprofeno/química , Cetoprofeno/farmacología , Concentración de Iones de Hidrógeno , Metacrilatos/química , Metacrilatos/farmacología , Acrilamidas/química , Acrilamidas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Temperatura , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Impresión Tridimensional

RESUMEN

The preparation of biodegradable and antibacterial hydrogels has important clinical value. In this work, a novel strategy has been developed to prepare degradable hydrogel dressings without chemical crosslinking agent using methacrylate anhydride (MA)-modified amylopectin (APMA) and polyacrylamide (PAM). After introducing CC bonds, APMA/PAM hydrogels can be formed under light irradiation. This strategy improves the gelling ability of AP and degradation properties of the hydrogel by avoiding the addition of crosslinking agent. The degradation rate of APMA/PAM hydrogel is 74.04 ± 0.69 % within 12 weeks, while that of APMA/PAM hydrogel containing crosslinking agent is only 38.5 ± 0.1 %. The APMA/PAM hydrogel loading curcumin (Cur) (APMA/PAM-Cur) exhibits high antibacterial efficiency of 98.29 ± 0.41 % and 97.18 ± 0.81 % against S. aureus and E. coli, respectively, with light irradiation. Animal experiments show that the APMA/PAM-Cur hydrogel reduces the infiltration of inflammatory factors, increases the density of collagen, and makes the newly formed granulation tissue thicker and tighter. This study not only proves the promising potential of the APMA/PAM-Cur hydrogel as degradable and antibacterial wound dressing for clinical treatment, but also provides a new strategy for developing low-cost, degradable, and antibacterial wound dressings and reducing antibiotic abuse and environmental pollution caused by medical waste.

Asunto(s)

Resinas Acrílicas , Antibacterianos , Vendajes , Curcumina , Hidrogeles , Cicatrización de Heridas , Curcumina/farmacología , Curcumina/química , Curcumina/administración & dosificación , Resinas Acrílicas/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Hidrogeles/química , Hidrogeles/farmacología , Animales , Cicatrización de Heridas/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Metacrilatos/química , Escherichia coli/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Ratones , Inyecciones

RESUMEN

Mucogingival surgery has been widely used in soft gingival tissue augmentation in which autografts are predominantly employed. However, the autografts face grand challenges, such as scarcity of palatal donor tissue and postoperative discomfort. Therefore, development of alternative soft tissue substitutes has been an imperative need. Here, we engineered an interconnected porous bovine serum albumin methacryloyl (BSAMA: B, as a drug carrier and antioxidant)/gelatin methacryloyl (GelMA: G, as a biocompatible collagen-like component)-based cryogel with L-Arginine (Arg) loaded as an angiogenic molecule, which could serve as a promising gingival tissue biohybrid scaffold. BG@Arg cryogels featured macroporous architecture, biodegradation, sponge-like properties, suturability, and sustained Arg release. Moreover, BG@Arg cryogels promoted vessel formation and collagen deposition which play an important role in tissue regeneration. Most interestingly, BG@Arg cryogels were found to enhance antioxidant effects. Finally, the therapeutic effect of BG@Arg on promoting tissue regeneration was confirmed in rat full-thickness skin and oral gingival defect models. In vivo results revealed that BG@Arg2 could promote better angiogenesis, more collagen production, and better modulation of inflammation, as compared to a commercial collagen membrane. These advantages might render BG@Arg cryogels a promising alternative to commercial collagen membrane products and possibly autografts for soft gingival tissue regeneration.

Asunto(s)

Arginina , Criogeles , Gelatina , Encía , Regeneración , Albúmina Sérica Bovina , Andamios del Tejido , Criogeles/química , Animales , Arginina/química , Arginina/farmacología , Ratas , Gelatina/química , Regeneración/efectos de los fármacos , Albúmina Sérica Bovina/química , Andamios del Tejido/química , Cicatrización de Heridas/efectos de los fármacos , Metacrilatos/química , Bovinos , Porosidad , Masculino , Antioxidantes/farmacología , Antioxidantes/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos/métodos , Ratas Sprague-Dawley

RESUMEN

BACKGROUND: Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. METHODS: GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. RESULTS: The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). CONCLUSIONS: The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ.

Asunto(s)

Osteonecrosis de los Maxilares Asociada a Difosfonatos , Gelatina , Heparina , Hidrogeles , Andamios del Tejido , Animales , Hidrogeles/uso terapéutico , Ratas , Osteonecrosis de los Maxilares Asociada a Difosfonatos/prevención & control , Fibrina Rica en Plaquetas , Microtomografía por Rayos X , Metacrilatos/química , Ratones , Ratas Sprague-Dawley , Diferenciación Celular/efectos de los fármacos , Masculino , Regeneración Ósea/efectos de los fármacos , Ácido Zoledrónico/uso terapéutico , Osteogénesis/efectos de los fármacos , Modelos Animales de Enfermedad

RESUMEN

OBJECTIVE: To formulate an experimental methacrylate-based photo-polymerizable resin for 3D printing with ytterbium trifluoride as filler and to evaluate the mechanical, physicochemical, and biological properties. METHODS: Resin matrix was formulated with 60 wt% UDMA, 40 wt% TEGDMA, 1 wt% TPO, and 0.01 wt% BHT. Ytterbium Trifluoride was added in concentrations of 1 (G1 %), 2 (G2 %), 3 (G3 %), 4 (G4 %), and 5 (G5 %) wt%. One group remained without filler addition as control (GC). The samples were designed in 3D builder software and printed using a UV-DLP 3D printer. The samples were ultrasonicated with isopropanol and UV cured for 60 min. The resins were tested for degree of conversion (DC), flexural strength, Knoop microhardness, softening in solvent, radiopacity, colorimetric analysis, and cytotoxicity (MTT and SRB). RESULTS: Post-polymerization increased the degree of conversion of all groups (p < 0.05). G2 % showed the highest DC after post-polymerization. G2 % showed no differences in flexural strength from the G1 % and GC (p > 0.05). All groups showed a hardness reduction after solvent immersion. No statistical difference was found in radiopacity, softening in solvent (ΔKHN%), colorimetric spectrophotometry, and cytotoxicity (MTT) (p > 0.05). G1 % showed reduced cell viability for SRB assay (p < 0.05). SIGNIFICANCE: It was possible to produce an experimental photo-polymerizable 3D printable resin with the addition of 2 % ytterbium trifluoride as filler without compromising the mechanical, physicochemical, and biological properties, comparable to the current provisional materials.

Asunto(s)

Dureza , Ensayo de Materiales , Metacrilatos , Impresión Tridimensional , Metacrilatos/química , Resistencia Flexional , Polimerizacion , Polietilenglicoles/química , Resinas Compuestas/química , Ácidos Polimetacrílicos/química , Poliuretanos/química , Colorimetría , Propiedades de Superficie

RESUMEN

The clinical failure mode of dental crown ceramics involves radial cracking at the interface, driven by the surface tension generated from the flexure of the ceramic layer on the subsurface. This results in a reduced lifespan for most all-ceramic dental crowns. Therefore, investigating optimal material combinations to reduce stress concentration in dental crown materials has become crucial for future successful clinical applications. The anisotropic complex structures of natural materials, such as nacre, could potentially create suitable strong and damage-resistant materials. Their imitation of natural structural optimisation and mechanical functionality at both the macro- and micro-levels minimises weaknesses in dental crowns. This research aims to optimise cost-effective, freeze-casted bioinspired composites for the manufacture of novel, strong, and tough ceramic-based dental crowns. To this end, multilayer alumina (Al2O3) composites with four different polymer phases were tested to evaluate their bending behaviour and determine their flexural strength. A computational model was developed and validated against the experimental results. This model includes Al2O3 layers that undergo gentle compression and distribute stress, while the polymer layers act as stress relievers, undergoing plastic deformation to reduce stress concentration. Based on the experimental data and numerical modelling, it was concluded that these composites exhibit variability in mechanical properties, primarily due to differences in microstructures and their flexural strength. Furthermore, the findings suggest that bioinspired Al2O3-based composites demonstrate promising deformation and strengthening behaviour, indicating potential for application in the dental field.

Asunto(s)

Óxido de Aluminio , Resinas Compuestas , Resistencia Flexional , Ensayo de Materiales , Óxido de Aluminio/química , Resinas Compuestas/química , Coronas , Materiales Dentales/química , Análisis del Estrés Dental , Poliuretanos/química , Cerámica/química , Metacrilatos/química , Polietilenglicoles/química , Propiedades de Superficie , Ácidos Polimetacrílicos/química , Análisis de Elementos Finitos , Estrés Mecánico