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1.
J Cell Physiol ; 236(8): 5715-5724, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33400284

RESUMEN

Periodontal ligament fibroblasts (PdLFs) are an elongated cell type in the periodontium with matrix and bone regulatory functions which become abnormal in periodontal disease (PD). Here we found that the normally elongated and oriented PdLF nucleus becomes rounded and loses orientation in a mouse model of PD. Using in vitro micropatterning of cultured primary PdLF cell shape, we show that PdLF elongation correlates with nuclear elongation and the presence of thicker, contractile F-actin fibers. The rounded nuclei in mouse PD models in vivo are, therefore, indicative of reduced actomyosin tension. Inhibiting actomyosin contractility by inhibiting myosin light chain kinase, Rho kinase or myosin ATPase activity, in cultured PdLFs each consistently reduced messenger RNA levels of bone regulatory protein osteoprotegerin (OPG). Infection of cultured PdLFs with two different types of periodontal bacteria (Porphyromonas gingivalis and Fusobacterium nucleatum) failed to recapitulate the observed nuclear rounding in vivo, upregulated nonmuscle myosin II phosphorylation and downregulated OPG. Collectively, our results add support to the hypothesis that PdLF contractility becomes decreased and contributes to disease progression in PD.


Asunto(s)
Actomiosina/metabolismo , Fibroblastos/metabolismo , Osteoprotegerina/metabolismo , Ligamento Periodontal/efectos de los fármacos , Animales , Citocinas/metabolismo , Interleucina-1beta/metabolismo , Ratones , Ratones Endogámicos C57BL , Ligamento Periodontal/metabolismo , Porphyromonas gingivalis/metabolismo
2.
Mol Cell Biochem ; 476(1): 303-310, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32989626

RESUMEN

Although tooth loss is a known risk factor of cognitive function, whether and how the chewing-side preference (CSP) affects memory impairment still remains unclear. This study evaluates the behavior changes in mice after the loss of teeth on one side and explores the role of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) signal pathway within these changes. To this end, CSP mouse models with either the removal of left unilateral molars (CSP-L) or right unilateral molars (CSP-R) were established. Morris water maze test and passive avoidance test were performed to evaluate the mice's learning and memory capacity in the 4th and 8th weeks. The correlation between CSP and brain function changes was validated with changes in 5-HT and BDNF levels. CSP mice's cognitive function was found to be decreased, along with a significant decline in 5-HT1A level, especially in CSP-R mice. BDNF and TrkB levels in CSP-R mice were also significantly lowered. These findings suggest that CSP results in memory impairment, which is associated with the 5-HT-BDNF signaling pathway.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/análisis , Masticación , Trastornos de la Memoria , Serotonina/análisis , Transducción de Señal , Animales , Reacción de Prevención , Conducta Animal , Cognición , Hipocampo , Masculino , Aprendizaje por Laberinto , Glicoproteínas de Membrana/metabolismo , Memoria , Ratones , Proteínas Tirosina Quinasas/metabolismo , Temperatura , Diente/fisiología
3.
Pharmacol Res ; 169: 105636, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33932606

RESUMEN

Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that proparacaine hydrochloride (PPC-HCl) exerted an acute robust antiepileptic effect in pilocarpine-induced epilepsy mice. More importantly, chronic treatment with PPC-HCl totally terminated spontaneous recurrent seizure occurrence without significant toxicity. Chronic treatment with PPC-HCl did not cause obvious cytotoxicity, neuropsychiatric adverse effects, hepatotoxicity, cardiotoxicity, and even genotoxicity that evaluated by whole genome-scale transcriptomic analyses. Only when in a high dose (50 mg/kg), the QRS interval measured by electrocardiography was slightly prolonged, which was similar to the impact of levetiracetam. Nevertheless, to overcome this potential issue, we adopt a liposome encapsulation strategy that could alleviate cardiotoxicity and prepared a type of hydrogel containing PPC-HCl for sustained release. Implantation of thermosensitive chitosan-based hydrogel containing liposomal PPC-HCl into the subcutaneous tissue exerted immediate and long-lasting remission from spontaneous recurrent seizure in epileptic mice without affecting QRS interval. Therefore, this new liposomal hydrogel formulation of proparacaine could be developed as a transdermal patch for treating epilepsy, avoiding the severe toxicity after chronic treatment with current antiepileptic drugs in clinic.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Epilepsia/tratamiento farmacológico , Propoxicaína/uso terapéutico , Animales , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Electroencefalografía , Suspensión Trasera , Hidrogeles , Liposomas/administración & dosificación , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones Endogámicos C57BL , Prueba de Campo Abierto/efectos de los fármacos , Propoxicaína/administración & dosificación , Propoxicaína/efectos adversos
4.
Anal Chem ; 92(11): 7581-7587, 2020 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-32367712

RESUMEN

The design and development of novel electrochemiluminescence (ECL) systems with near-infrared (NIR) emission beyond 800 nm are promising for ECL evolution, especially for improving the throughput of the spectrum-resolved multiplexing ECL assay and biological imaging. Herein a biocompatible and environmentally friendly luminophore, that is, the methionine-stabilized Au nanoclusters (Met-Au NCs), are proposed to achieve efficient aqueous ECL of ∼835 nm with triethanolamine as coreactant. The Met-Au NCs not only demonstrate a 75 times enhanced ECL compared with the traditional Au NCs with bovine serum albumin as a capping agent but also can be employed as ECL tags to label proteins with a methionine linker and enable a highly sensitive NIR ECL bioassay. A sandwich-type NIR ECL immunosensor is constructed with the Met-Au NCs as tags and α-fetoprotein (AFP) as a model analyte and exhibits a wide linearity range from 3 fg·mL-1 to 0.1 ng·mL-1 with a limit of detection of 1 fg mL-1 (S/N = 3) as well as desired selectivity.


Asunto(s)
Materiales Biocompatibles/química , Técnicas Biosensibles , Técnicas Electroquímicas , Inmunoensayo , Mediciones Luminiscentes , alfa-Fetoproteínas/análisis , Oro/química , Humanos , Rayos Infrarrojos , Nanopartículas del Metal/química
5.
Macromol Rapid Commun ; 40(17): e1800731, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30672634

RESUMEN

A new type of dynamic covalent macrocycle with self-promoted supramolecular gelation behavior is developed. Under oxidative conditions, the dithiol compound containing a diamide alkyl linker with an odd number (7) of carbon chain and an appended crown ether shows a remarkable gelation ability in acetonitrile, without any template molecules. Due to the existence of crown ethers and disulfide bonds, the obtained gel shows a multiple stimuli-responsiveness behavior. The mechanical properties and reversibility of the gel are investigated. Computational modeling suggests that the peripheral chain for diamide hydrogen bonding is responsible for the gelation process.


Asunto(s)
Materiales Biocompatibles/química , Coloides/química , Éteres Corona/química , Geles/química , Compuestos Macrocíclicos/química , Simulación por Computador , Enlace de Hidrógeno , Estructura Molecular
6.
J Am Chem Soc ; 140(6): 2165-2178, 2018 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-29376345

RESUMEN

The development of activatable nanoplatforms to simultaneously improve diagnostic and therapeutic performances while reducing side effects is highly attractive for precision cancer medicine. Herein, we develop a one-pot, dopamine-mediated biomineralization method using a gas diffusion procedure to prepare calcium carbonate-polydopamine (CaCO3-PDA) composite hollow nanoparticles as a multifunctional theranostic nanoplatform. Because of the high sensitivity of such nanoparticles to pH, with rapid degradation under a slightly acidic environment, the photoactivity of the loaded photosensitizer, i.e., chlorin e6 (Ce6), which is quenched by PDA, is therefore increased within the tumor under reduced pH, showing recovered fluorescence and enhanced singlet oxygen generation. In addition, due to the strong affinity between metal ions and PDA, our nanoparticles can bind with various types of metal ions, conferring them with multimodal imaging capability. By utilizing pH-responsive multifunctional nanocarriers, effective in vivo antitumor photodynamic therapy (PDT) can be realized under the precise guidance of multimodal imaging. Interestingly, at normal physiological pH, our nanoparticles are quenched and show much lower phototoxicity to normal tissues, thus effectively reducing skin damage during PDT. Therefore, our work presents a unique type of biomineralized theranostic nanoparticles with inherent biocompatibility, multimodal imaging functionality, high antitumor PDT efficacy, and reduced skin phototoxicity.


Asunto(s)
Carbonato de Calcio/química , Indoles/química , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Polímeros/química , Porfirinas/uso terapéutico , Animales , Línea Celular Tumoral , Clorofilidas , Preparaciones de Acción Retardada/química , Femenino , Concentración de Iones de Hidrógeno , Imagen por Resonancia Magnética/métodos , Ratones , Ratones Endogámicos BALB C , Imagen Multimodal/métodos , Imagen Óptica/métodos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Porfirinas/administración & dosificación , Nanomedicina Teranóstica/métodos
7.
Clin Oral Investig ; 20(8): 2259-2265, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26814714

RESUMEN

OBJECTIVES: Guided bone regeneration (GBR) aims to predictably restore missing bone that has been lost due to trauma, periodontal disease or a variety of systemic conditions. Critical to this procedure is the ability of a bone grafting material to predictably serve as a 3-dimensional scaffold capable of inducing cell and bone tissue in-growth at the material surface. Although all bone grafts are osteoconductive to bone-forming osteoblasts, only a small number of commercially available bone grafts with FDA approval are osteoinductive including demineralized freeze-dried bone allographs (DFDBA) and scaffolds containing bone morphogenetic proteins (BMPs). Recently, a class of synthetic bone grafts fabricated from biphasic calcium phosphate (BCP) sintered at a low temperature have been shown to form ectopic bone formation in non-skeletal sites without the use of growth factors. Therefore, the present study aimed to compare the osteoinductive potential of this group of synthetic BCP alloplasts with autografts, allografts and xenografts. MATERIALS AND METHODS: In the present study, 4 types of bone grafting materials including autogenous bone harvested with a bone mill, DFDBA (LifeNet, USA), a xenograft derived from bovine bone mineral (NBM, BioOss, Geistlich, Switzerland) and a novel synthetic biphasic calcium phosphate (BCP, Straumman, Switzerland) were implanted into intramuscular pouches of 24 rats and analysed histologically for their ability to form ectopic bone formation around grafting particles. A semi-quantitative osteoinductive score was used to quantify the osteoinductive ability of each bone graft. RESULTS: The results from the present study reveal that (1) autogenous bone resorbed rapidly in vivo, (2) the xenograft showed no potential to form ectopic bone formation and (3) both DFDBA and BCP were able to stimulate ectopic bone formation. CONCLUSION: These studies demonstrate that these newly developed synthetic bone grafts have potential for inducing ectopic bone formation similar to DFDBA. Future clinical testing is necessary to reveal their bone-inducing properties in clinical scenarios including GBR procedures and in combination with implant dentistry. CLINICAL RELEVANCE: Novel BCP scaffolds are able to induce ectopic bone formation without the use of osteoinductive growth factors such as BMP2 and thus demonstrate a large clinical possibility to further enhance bone formation for a variety of clinical procedures.


Asunto(s)
Sustitutos de Huesos/farmacología , Hidroxiapatitas/farmacología , Osteogénesis/efectos de los fármacos , Aloinjertos , Animales , Proteínas Morfogenéticas Óseas/farmacología , Trasplante Óseo/métodos , Bovinos , Liofilización , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Minerales , Ratas , Ratas Wistar , Propiedades de Superficie
8.
BMC Genet ; 15: 20, 2014 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-24507412

RESUMEN

BACKGROUND: In a natural population, the alleles of multiple tightly linked loci on the same chromosome co-segregate and are passed non-randomly from generation to generation. Capitalizing on this phenomenon, a group of mapping methods, commonly referred to as the linkage disequilibrium-based mapping (LD mapping), have been developed recently for detecting genetic associations. However, most current LD mapping methods mainly employed single-marker analysis, overlooking the rich information contained within adjacent linked loci. RESULTS: We extend the single-marker LD mapping to include two linked loci and explicitly incorporate their LD information into genetic mapping models (tmLD). We establish the theoretical foundations for the tmLD mapping method and also provide a thorough examination of its statistical properties. Our simulation studies demonstrate that the tmLD mapping method significantly improves the detection power of association compared to the single-marker based and also haplotype based mapping methods. The practical usage and properties of the tmLD mapping method were further elucidated through the analysis of a large-scale dental caries GWAS data set. It shows that the tmLD mapping method can identify significant SNPs that are missed by the traditional single-marker association analysis and haplotype based mapping method. An R package for our proposed method has been developed and is freely available. CONCLUSIONS: The proposed tmLD mapping method is more powerful than single marker mapping generally used in GWAS data analysis. We recommend the usage of this improved method over the traditional single marker association analysis.


Asunto(s)
Mapeo Cromosómico/métodos , Desequilibrio de Ligamiento , Sitios de Carácter Cuantitativo , Algoritmos , Simulación por Computador , Caries Dental/genética , Estudio de Asociación del Genoma Completo , Haplotipos , Humanos , Funciones de Verosimilitud , Modelos Genéticos , Polimorfismo de Nucleótido Simple
9.
Zhongguo Zhong Yao Za Zhi ; 39(15): 2915-7, 2014 Aug.
Artículo en Zh | MEDLINE | ID: mdl-25423832

RESUMEN

OBJECTIVE: To establish the method for determining polysorbate 80 in Reduning injection by HPLC-ELSD, and to control the mass of polysorbate 80 in Reduning injection. METHOD: It was performed by HGPC-ELSD with TOSHTSK-GEL G4000PWxl (7.8 mm x 300 mm, 10 µm). Water was used as mobile phase, the flow rate was 0.7 mL x min(-1), and the temperature was set at 30°C. The evaporated light scattering detector was adopted. The drift tube temperature was 55°C, and nitrogen was used as carrier gas, with the flow rate of 2.0 L x min(-1) and gain of 1.0. RESULT: The calibration curve showed good linearity of polysorbate 80 in the test range from 1.01 to 15.20 g x L(-1) (r2 = 0.999 3). The recovery rate was 98.10% with RSD of 2.0%. CONCLUSION: The method is simple, rapid, accurate and reliable and suitable for the determination of polysorbate 80 in Reduning injection.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Polisorbatos/análisis , Calibración , Inyecciones , Reproducibilidad de los Resultados , Factores de Tiempo
10.
Talanta ; 270: 125640, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38211357

RESUMEN

Herein, the excitation wavelength-dependent responses of the molecularly imprinted polymer (MIP) photoelectrochemical (PEC) sensors were investigated, using acetaminophen (AP), rutin (RT) and perfluorooctanoate (PFOA) as the model templates, pyrrole as functional monomer, CuInS2@ZnS/TiO2 NTs as the basic photoelectrode. With wavelength λ > 240 nm, the photocurrent of MIPPFOA enhanced at higher concentrations of PFOA. With increasing AP concentration, the photocurrents of MIPAP could decline with λ < 271 nm, not change at λ = 270 nm, or increase with λ > 270 nm. As RT concentration increased, the photocurrents of MIPRT could decrease (λ < 431 nm), not change (λ = 431 nm) or increase (λ > 431 nm). The PEC responses depend on the comprehensive interaction of two contrary mechanisms from the template molecules within the MIP membrane. The photocurrent is enhanced by the role of the electron donor for photo-generated holes but attenuated due to the steric hindrance effect and the excitation light intensity loss via absorption or scattering. The apparent molar absorption coefficient of AP and RT within MIP membranes are 9.1-19.4 folds of those measured from dilute solutions. By using a routine UV lamp as the light source, the photocurrents of MIPRT at 254 nm and MIPAP at 365 nm were used to determine RT and AP, with the detection limits of 5.3 and 16 nM, respectively. The interference from the non-specific adsorption of interferents on the surfaces of MIPAP and MIPRT was reduced by one order of magnitude via a differential strategy.


Asunto(s)
Impresión Molecular , Polímeros Impresos Molecularmente , Acetaminofén , Polímeros/química , Rutina , Luz , Límite de Detección , Técnicas Electroquímicas
11.
Int J Nanomedicine ; 19: 1273-1285, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38348176

RESUMEN

Purpose: To investigate the inhibition of Streptococcus mutans (S.mutans) and its biofilm by AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) and evaluate the changes in Polymethyl methacrylate (PMMA)'s surface roughness (Ra), microhardness, and flexural strength during prolonged immersion in AgBr-NP@CTMAB for application in the denture cleaning industry. Patients and Methods: The antibacterial activity of AgBr-NP@CTMAB against S.mutans was measured colony formation assay, OD600 and laser confocal microscopy. Changes in the specimens' values for surface roughness, microhardness, and flexural strength (MPa) were measured after immersion solutions for 180 or 360 days. Results: The AgBr-NP@CTMAB solution exhibited a robust antibacterial effect on planktonic S. mutans, with a minimum bactericidal concentration of 5 µg/mL. The 10 µg/mL AgBr-NP@CTMAB solution efficiently inhibited S. mutans biofilm formation. (2) No significant difference in surface roughness after immersion in AgBr-NP@CTMAB (10 µg/mL and 20 µg/mL) comparing with distilled water (P > 0.05) and Polident had significantly higher than distilled water (P < 0.05). There was a significant decrease in the surface hardness of the PMMA specimens that were immersed in the Polident compared with those in distilled water (P < 0.05). While, no significant differences in surface hardness after immersion in the AgBr-NP@CTMAB (P > 0.05). The result of flexural strength suggested that there was no statistically significant difference (P < 0.05) between AgBr-NP@CTMAB as well as Polident and water. Conclusion: AgBrNP@CTMAB can efficiently inhibit the growth of plankton S.mutans and biofilm formation, without affecting the flexural strength, microhardness, or surface roughness of PMMA. Therefore, AgBrNP@CTMAB holds promise as a new denture cleaning agent.


Asunto(s)
Boratos , Nanopartículas , Polimetil Metacrilato , Sulfatos , Dureza , Resistencia Flexional , Streptococcus mutans , Bases para Dentadura , Agua , Antibacterianos/farmacología , Propiedades de Superficie , Ensayo de Materiales
12.
J Control Release ; 368: 676-690, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38458572

RESUMEN

Barrier membranes play a pivotal role in the success of guided periodontal tissue regeneration. The biodegradable barriers predominantly used in clinical practice often lack sufficient barrier strength, antibacterial properties, and bioactivity, frequently leading to suboptimal regeneration outcomes. Although with advantages in mechanical strength, biodegradability and plasticity, bioinert aliphatic polyesters as barrier materials are usually polymerized via toxic catalysts, hard to be functionalized and lack of antibacterial properties. To address these challenges, we propose a new concept that controlled release of bioactive substance on the whole degradation course can give a bioinert aliphatic polyester bioactivity. Thus, a Zn-based catalytic system for polycondensation of dicarboxylic acids and diols is created to prepare zinc covalent hybrid polyester (PBS/ZnO). The atomically-dispersed Zn2+ ions entering main chain of polyester molecules endow PBS/ZnO barrier with antibacterial properties, barrier strength, excellent biocompatibility and histocompatibility. Further studies reveal that relying on long-term controlled release of Zn2+ ions, the PBS/ZnO membrane greatly expedites osteogenetic effect in guided tissue regeneration (GTR) by enhancing the mitochondrial function of macrophages to induce M2 polarization. These findings show a novel preparation strategy of bioactive polyester biomaterials based on long term controlled release of bioactive substance that integrates catalysis, material structures and function customization.


Asunto(s)
Regeneración Tisular Dirigida , Óxido de Zinc , Zinc , Poliésteres/química , Preparaciones de Acción Retardada , Antibacterianos/farmacología , Antibacterianos/química , Iones , Regeneración Ósea
13.
J Mater Chem B ; 11(27): 6308-6318, 2023 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-37326438

RESUMEN

Long-gap peripheral nerve injury remains a major challenge in regenerative medicine and results in permanent sensory and motor dysfunction. Nerve guidance scaffolds (NGSs) are known as a promising alternative to autologous nerve grafting. The latter, the current "gold standard" in clinical practice, is frequently constrained by the limited availability of sources and the inevitable damage to the donor area. Given the electrophysiological properties of nerves, electroactive biomaterials are being intensively investigated in nerve tissue engineering. In this study, we engineered a conductive NGS compounded of biodegradable waterborne polyurethane (WPU) and polydopamine-reduced graphene oxide (pGO) for repairing impaired peripheral nerves. The incorporation of pGO at the optimal concentration (3 wt%) promoted in vitro spreading of Schwann cells (SCs) with high expression of the proliferation marker S100 protein. In an in vivo study of sciatic nerve transection injury, WPU/pGO NGSs were found to regulate the immune microenvironment by activating macrophage M2 polarization and upregulate growth-associated protein 43 (GAP43) to facilitate axonal elongation. Histological and motor function analysis demonstrated that WPU/pGO NGSs had a neuroprosthetic effect close to that of an autograft, which significantly promoted the regeneration of myelinated axons, reduced gastrocnemius atrophy, and enhanced hindlimb motor function. These findings together suggested that electroactive WPU/pGO NGSs may represent a safe and effective strategy to manage large nerve defects.


Asunto(s)
Traumatismos de los Nervios Periféricos , Neuropatía Ciática , Animales , Poliuretanos , Conos de Crecimiento/metabolismo , Conos de Crecimiento/patología , Nervios Periféricos/fisiología , Regeneración Nerviosa/fisiología , Traumatismos de los Nervios Periféricos/tratamiento farmacológico
14.
J Mater Chem B ; 11(10): 2115-2128, 2023 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-36779440

RESUMEN

Decellularized extracellular matrix (dECM) nerve guide conduits (NGCs) are a promising strategy to replace autogenous nerve grafting for the treatment of peripheral nerve system (PNS) injury. However, dECM conduits with mechanical properties that match those of peripheral nerves are yet to be well developed. Herein, we developed polyurethane-based NGCs incorporating decellularized spinal cord (BWPU-DSC NGCs) to repair peripheral nerves. BWPU-DSC NGCs have an inner three-dimensional micro-nanostructure. The mechanical properties of BWPU-DSC NGCs were similar to those of polyurethane NGCs, which were proven to promote peripheral nerve regeneration. An in vitro study indicated that BWPU-DSC NGCs could boost the proliferation and growth of cell processes in Schwann and neuron-like cells. In a rat sciatic nerve transected injury model, BWPU-DSC NGCs exhibited a dramatic increase in nerve repair, similar to that obtained by the current gold standard autograft implantation at only 6 weeks post-implantation, whereas polyurethane NGCs still displayed incomplete nerve repair. Histological analysis revealed that BWPU-DSC NGCs could induce the reprogramming of Schwann cells to promote axon regeneration and remyelination. Moreover, reprogrammed Schwann cells together with BWPU-DSC NGCs had anti-inflammatory effects and altered the activation state of macrophages to M2 phenotypes to enhance PNS regeneration. In this study, we provided a strategy to prepare polyurethane-based dECM NGCs enriched with bioactive molecules to promote PNS regeneration.


Asunto(s)
Regeneración Tisular Dirigida , Traumatismos de los Nervios Periféricos , Ratas , Animales , Axones , Poliuretanos/farmacología , Regeneración Tisular Dirigida/métodos , Regeneración Nerviosa , Reprogramación Celular , Nervios Periféricos , Células de Schwann , Traumatismos de los Nervios Periféricos/terapia
15.
J Mater Chem B ; 11(14): 3136-3150, 2023 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-36896831

RESUMEN

Craniomaxillofacial bone defects result in physical and psychological dual injuries making the promotion or acceleration of bone regeneration imperative. In this work, a fully biodegradable hydrogel is facilely prepared via thiol-ene "click" reactions under human physiological conditions using multifunctional poly(ethylene glycol) (PEG) derivatives as precursors. This hydrogel shows excellent biological compatibility, enough mechanical strength, a low swelling rate and an appropriate degradation rate. Rat bone marrow mesenchymal stem cells (rBMSCs) can survive and proliferate on/in the PEG hydrogel and differentiate into osteogenic cells. The PEG hydrogel can also effectively load rhBMP-2 through the above "click" reaction. Under the physical barrier of the chemically crosslinked hydrogel network, the spatiotemporal release of rhBMP-2 effectively promotes the proliferation and osteogenic differentiation of rBMSCs at a loading concentration of 1 µg ml-1. Finally, based on a rat calvarial critical-size defect model, the rhBMP-2 immobilized hydrogel loaded with rBMSCs basically accomplishes the repair and regeneration within 4 weeks featured by remarkably enhanced osteogenesis and angiogenesis. The click-based injectable bioactive PEG hydrogel developed in the present study is a new type of bone substitute with great expectations in future clinical applications.


Asunto(s)
Regeneración Ósea , Osteogénesis , Animales , Humanos , Ratas , Materiales Biocompatibles/farmacología , Hidrogeles/farmacología , Polietilenglicoles/farmacología , Proteínas Recombinantes/farmacología , Proteína Morfogenética Ósea 2/farmacología
16.
J Phys Chem B ; 126(46): 9726-9736, 2022 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-36378585

RESUMEN

Biphasic calcium phosphate (BCP) is used as a bone substitute and bone tissue repair material due to its better control over bioactivity and biodegradability. It is crucial to stabilize the implanted biomaterial while promoting bone ingrowth. However, a lack of standard experimental and theoretical protocols to characterize the physicochemical properties of BCP limits the optimization of its composition and properties. Computational simulations can help us better to learn BCP at a nanoscale level. Here, the Voronoi tessellation method was combined with simulated annealing molecular dynamics to construct BCP nanoparticle models of different sizes, which were used to understand the physicochemical properties of BCP (e.g., melting point, infrared spectrum, and mechanical properties). We observed a ∼20 to 30 Å layer of calcium-deficient hydroxyapatite at the HAP/ß-TCP interface due to particle migration, which may contribute to BCP stability. The BCP model may stimulate further research into BCP ceramics and multiphasic ceramics. Moreover, our study may facilitate the optimization of compositions of BCP-based biomaterials.


Asunto(s)
Simulación de Dinámica Molecular , Nanopartículas , Biomimética , Hidroxiapatitas/química , Fosfatos de Calcio/química , Durapatita/química , Cerámica/química , Materiales Biocompatibles/química , Nanopartículas/química
17.
J Mater Chem B ; 10(43): 8918-8930, 2022 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-36259986

RESUMEN

Shape memory polymers (SMPs) with multiple functionalities have great potential in implantable biomedical devices, especially vascular stents. However, stents made of SMPs are generally faced with the problem of insufficient radial support due to the sharp decline of the modulus after shape recovery. Therefore, it is necessary to improve the modulus of SMPs after opening the narrow part by other means. In this study, the novel SMPs available for vascular stents were developed with impressive water-induced stiffening when shape recovered in a physiological environment. Herein, a series of shape memory polyurethanes (SMPUs) containing full hard segments on the main chains and bearing hydrophilic tertiary amine soft segments on the side chains were synthesized. When immersed in water, the soft segments were dramatically separated from the hard segments, which were aggregated more to form densely packed hard domains with stronger hydrogen bonding and higher crystallinity. Both Young's modulus and the shape recovery ratio were thus promoted due to the segmental rearrangement in water. At the same time, hydrophilic side chains migrated to the surface driven by the segmental rearrangement in water, which promotes the adhesion and growth of vascular endothelial cells and inhibits the activation of the coagulation system. The ingenious structural design provided SMPUs with adequate mechanical strength and hemocompatibility to qualify for potential applications in self-expanding vascular stents.


Asunto(s)
Poliuretanos , Materiales Inteligentes , Poliuretanos/química , Agua , Células Endoteliales , Stents
18.
J Mater Chem B ; 9(38): 7979-7990, 2021 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-34612287

RESUMEN

Nerve guide conduits (NGCs) can replace autogenous nerve grafting in the treatment of peripheral nerve system (PNS) injury. However, the modulus of polyurethane NGCs that affects the outcome of PNS repair has been rarely elucidated in vivo. In this study, we developed biodegradable waterborne polyurethane (BWPU) NGCs with an outer BWPU membrane and an inner three-dimensional scaffold structure. The mechanical properties of BWPU NGCs can be modified by adjusting the molar content of polyethylene glycol (PEG) in the soft segments within the BWPU. Two types of BWPU NGCs with different moduli were prepared, containing 17% and 25% PEG in BWPU (termed as BWPU 17 NGCs and BWPU 25 NGCs, respectively). In rat sciatic nerves with 10-mm transected injury, mechanically stronger BWPU 17 NGCs exhibited superior nerve repair, which was similar to that obtained by the current gold standard autograft implantation, whereas weaker BWPU 25 NGCs displayed an unsatisfactory effect. Histological results revealed that both BWPU NGCs had anti-inflammatory effects and altered the activation state of macrophages to M2 phenotypes to enhance PNS regeneration. The analysis of growth-associated protein 43 expression, which regulates axon growth, revealed that the mechanical properties of BWPU NGCs influence the outcome of PNS regeneration by affecting the formation and extension of axons. These findings suggest that the mechanical properties of NGCs could play a key role in regulating PNS repair and should be considered in future biomaterial NGC designs.


Asunto(s)
Axones/fisiología , Materiales Biocompatibles/uso terapéutico , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos/terapia , Poliuretanos/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Adhesión Celular/efectos de los fármacos , Femenino , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Músculo Esquelético/patología , Regeneración Nerviosa/efectos de los fármacos , Traumatismos de los Nervios Periféricos/patología , Polietilenglicoles/química , Poliuretanos/farmacología , Poliuretanos/uso terapéutico , Ratas , Ratas Sprague-Dawley , Nervio Ciático/fisiología
19.
Int J Nanomedicine ; 16: 3091-3103, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33953557

RESUMEN

OBJECTIVE: To synthesize and determine the antifungal activity of AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) against Candida albicans (C. albicans) for use in the field of denture cleaning. METHODS: The morphology and structure of AgBr-NP@CTMAB were characterized by IR, UV-Vis, XRD and SEM. The antifungal potential of AgBr-NP@CTMAB against C. albicans was determined by colony formation assay and growth curve analysis. PMMA containing AgBr-NP@CTMAB was prepared, and the long-term antifungal efficacy was analyzed. The effect against C. albicans biofilm was analyzed by SEM and OD600 , and the color changes of the specimens were observed by stereomicroscopy after 1 week of incubation. Cytotoxicity to human oral gingival fibroblasts and oral mucosal epithelial cells was detected by Cell Counting Kit-8 (CCK-8) in vitro. RESULTS: The compound showed a good crystalline phase, the presence of AgBr nanoparticles and the hybridization of CTMAB+ with AgBr-NPs. AgBr-NP@CTMAB showed significant antifungal activity against C. albicans at concentrations of 10 µg/mL and 20 µg/mL. PMMA specimens containing AgBr-NP@CTMAB showed no long-term antifungal effect against C. albicans biofilm. The clearance rate of C. albicans attached to PMMA was 44.73% after soaking in 10 µg/mL AgBr-NP@CTMAB solution for 30 min and 91.35% for 8 h. There was no significant residual cytotoxicity or visual color change after soaking. SIGNIFICANCE: AgBr-NP@CTMAB showed promising potential treatment for denture cleaners.


Asunto(s)
Antifúngicos/síntesis química , Antifúngicos/farmacología , Cetrimonio/química , Nanopartículas/química , Polimetil Metacrilato/química , Antifúngicos/química , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Candida albicans/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Candida albicans/fisiología , Técnicas de Química Sintética , Humanos , Nanotecnología
20.
Anal Chim Acta ; 1125: 201-209, 2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32674767

RESUMEN

Molecularly imprinting polymers (MIPs), as artificial antibodies with high recognition selectivity to template molecules, are widely used in various biosensors. To improve further the selectivity of MIPs-based photoelectrochemical (PEC) biosensors, we report a differential strategy using non-imprinted polymers (NIPs) as the reference. In a proof-to-concept example for the determination of dopamine (DA), MIPs and NIPs membranes were fabricated by electrochemical polymerization of polypyrrole membranes on the surface of graphene quantum dots (GQDs)/TiO2 nanotubes (NTs). The photocurrent difference between the two PEC cells, MIPs@GQDs/TiO2 NTs-Pt and NIPs@GQDs/TiO2 NTs-Pt, was measured as the signal. As the non-specific adsorption of non-template molecules on the outside surface of MIPs and NIPs membranes is similar, the anti-interference ability for the determination of DA is much improved by using differential strategy. In the normal and differential PEC measurement models, 10.0 µM ascorbic acid is equivalent to 3.12 and 0.40 µM DA, respectively. Further, the smaller specific surface area in NIPs membrane was compensated by using a weight factor to correct the residual interference in a modified differential model. By using 10.0 µM ascorbic acid as the balance point, the presence of 10.0 µM H2O2, glutathione, uric acid or glucose is equivalent only to 0.090, 0.061,0.11 or 0.041 µM of DA, respectively, which are about 3-7% of their interference levels in the normal photocurrent model. The differential PEC method was applied in the determination of DA in serum samples in the linear range of 0.05-12.5 µM, with the detection limit of 0.018 µM.


Asunto(s)
Dopamina/sangre , Técnicas Electroquímicas/métodos , Polímeros Impresos Molecularmente/química , Técnicas Biosensibles/métodos , Grafito/química , Humanos , Luz , Límite de Detección , Impresión Molecular/métodos , Nanotubos/química , Nanotubos/efectos de la radiación , Fotoquímica/métodos , Polímeros/química , Prueba de Estudio Conceptual , Pirroles/química , Puntos Cuánticos/química , Reproducibilidad de los Resultados , Titanio/química , Titanio/efectos de la radiación
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