RESUMO
Polyvinylidene fluoride (PVDF) and its copolymer with trifluoroethylene (P(VDF-TrFE)) are considered as promising biomaterials for supporting nerve regeneration because of their proven biocompatibility and piezoelectric properties that could stimulate cell ingrowth due to their electrical activity upon mechanical deformation. For the first time, this study reports on the comparative analysis of PVDF and P(VDF-TrFE) electrospun scaffolds in terms of structural and piezoelectric properties as well as their in vitro performance. A dynamic impact test machine was developed, validated, and utilised, to evaluate the generation of an electrical voltage upon the application of an impact load (varying load magnitude and frequency) onto the electrospun PVDF (15-20 wt%) and P(VDF-TrFE) (10-20 wt%) scaffolds. The cytotoxicity and in vitro performance of the scaffolds was evaluated with neonatal rat (nrSCs) and adult human Schwann cells (ahSCs). The neurite outgrowth behaviour from sensory rat dorsal root ganglion neurons cultured on the scaffolds was analysed qualitatively. The results showed (i) a significant increase of the ß-phase content in the PVDF after electrospinning as well as a zeta potential similar to P(VDF-TrFE), (ii) a non-constant behaviour of the longitudinal piezoelectric strain constant d33, depending on the load and the load frequency, and (iii) biocompatibility with cultured Schwann cells and guiding properties for sensory neurite outgrowth. In summary, the electrospun PVDF-based scaffolds, representing piezoelectric activity, can be considered as promising materials for the development of artificial nerve conduits for the peripheral nerve injury repair.
Assuntos
Polímeros de Fluorcarboneto/química , Gânglios Espinais/fisiologia , Hidrocarbonetos Fluorados/química , Regeneração Nervosa , Polivinil/química , Células de Schwann/fisiologia , Alicerces Teciduais , Adolescente , Adulto , Animais , Materiais Biocompatíveis , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polímeros , Ratos , Adulto JovemRESUMO
Theranostic systems enable early cancer diagnostic and treatment. In this work, we prepared Na-caseinate coated magnetic nanoparticles (MNP) to assess their capability as a theranostic system. This system enables monitoring by magnetic particle imaging (MPI), drug delivery and magnetic hyperthermia. MNP were synthesized in a continuous flow, coated with Na-caseinate and enzymatically crosslinked with transglutaminase to increase their colloidal stability and enable drug loading. They were investigated concerning their magnetic behaviour by DC magnetization measurements (DCM), magnetic particle spectroscopy (MPS) and AC-magnetometry to evaluate their suitability for MPI and hyperthermia. Further, their stability in different salt solutions as well as their encapsulation efficiency with a hydrophobic model drug (nile red), cell viability and uptake were investigated. Our results show that the Na-caseinate coating of MNP marginally effects the magnetic behaviour of the MNP with a consistent magnetization saturation M S of 109(5) A m2 per kg(Fe) for uncoated and casein coated MNP and with a decrease of <15% of A 3*, but only a slight decrease of 2% of A 5/A 3 for Na-caseinate coated MNP. Furthermore, the Na-caseinate coating of MNP increased their salt stability, under unchanged magnetic behaviour. Drug loading (up to â¼75%) and release kinetics such as the delivery into cutaneous squamous cell carcinoma cells (SCL-1) was shown. Our results demonstrate that casein coated MNP are highly promising candidates for theranostic applications in drug delivery, magnetic hyperthermia and magnetic particle imaging.
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Bacterial adhesion to dental implants is the onset for the development of pathological biofilms. Reliable characterization of this initial process is the basis towards the development of anti-biofilm strategies. In the present study, single-cell force spectroscopy (SCFS), by means of an atomic force microscope connected to a microfluidic pressure control system (FluidFM), was used to comparably measure adhesion forces of different oral bacteria within a similar experimental setup to the common implant material titanium. The bacteria selected belong to different ecological niches in oral biofilms: the commensal pioneers Streptococcus oralis and Actinomyces naeslundii; secondary colonizer Veillonella dispar; and the late colonizing pathogens Porphyromonas gingivalis as well as fimbriated and non-fimbriated Aggregatibacter actinomycetemcomitans. The results showed highest values for early colonizing pioneer species, strengthening the link between adhesion forces and bacteria's role in oral biofilm development. Additionally, the correlation between biophysical cellular characteristics and SCFS results across species was analyzed. Here, distinct correlations between electrostatically driven maximum adhesion force, bacterial surface elasticity and surface charge as well as single-molecule attachment points, stretching capability and metabolic activity, could be identified. Therefore, this study provides a step towards the detailed understanding of oral bacteria initial adhesion and could support the development of infection-resistant implant materials in future.
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Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood, and new effective pharmacological treatments are desired. Here, using a bidirectional neuromodulation approach, we demonstrate a causal link between reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. A neuron-specific prefrontal mGluR2 knockdown in rats generated a phenotype of reduced cognitive flexibility and excessive alcohol seeking. Conversely, virally restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. In the search for a pharmacological intervention with high translational potential, psilocybin was capable of restoring mGluR2 expression and reducing relapse behavior. Last, we propose a FDG-PET biomarker strategy to identify mGluR2 treatment-responsive individuals. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving and provided a personalized mGluR2 mechanism-based intervention strategy for medication development for alcoholism.
RESUMO
Clinically used infusion solutions are complex aqueous mixtures composed of a variety of different salts, acids, and non-electrolytes, and are characterized by composition, initial pH, and titratable acidity (TA). By rigorous treatment as a multi-composed acid-base system, pH and TA were calculated from proton dissociation equilibria, mass balance equations and electroneutrality condition. Nine were arbitrarily chosen as model solutions in which pH and TA were experimentally determined. From composition, and based on a set of apparent acidity constants (pK values) at 37 degrees C and total ionic strength 0.155 mol/l, pH was calculated by iteration. In the model solutions, measured pH was in the range 5-7, and the difference between calculated and experimental values was+/-0.064. Good agreement was also found between calculated and measured TA: in the range 0-55 mmol/l the mean difference was+/-2.07 mmol/l, if calculated from measured pH, and +/-0.95 mmol/l, if calculated from calculated pH.