Understanding the mechanics of the respiratory system is crucial for optimizing ventilator settings and ensuring patient safety. While simple models of the respiratory system typically consider only flow resistance and lung compliance, lung tissue resistance is usually neglected. This study investigated the effect of lung tissue viscoelasticity on delivered mechanical power in a physical model of the respiratory system and the possibility of distinguishing tissue resistance from airway resistance using proximal pressure measured at the airway opening. Three different configurations of a passive physical model of the respiratory system representing different mechanical properties (Tissue resistance model, Airway resistance model, and No-resistance model) were tested. The same volume-controlled ventilation and parameters were set for each configuration, with only the inspiratory flow rates being adjusted. Pressure and flow were measured with a Datex-Ohmeda S/5 vital signs monitor (Datex-Ohmeda, Madison, WI, USA). Tissue resistance was intentionally tuned so that peak pressures and delivered mechanical energy measured at airway opening were similar in Tissue and Airway Resistance models. However, measurements inside the artificial lung revealed significant differences, with Tissue resistance model yielding up to 20% higher values for delivered mechanical energy. The results indicate the need to revise current methods of calculating mechanical power delivery, which do not distinguish between tissue resistance and airway flow resistance, making it difficult to evaluate and interpret the significance of mechanical power delivery in terms of lung ventilation protectivity.
BACKGROUND: The purpose of dermal substitutes is to mimic the basic properties of the extracellular matrix of human skin. The application of dermal substitutes to the defect reduces the formation of hypertrophic scars and improves the scar quality. This study aims to develop an original dermal substitute enriched with stable fibroblast growth factor 2 (FGF2-STAB®) and test it in an animal model. METHODS: Dermal substitutes based on collagen/chitosan scaffolds or collagen/chitosan scaffolds with nanofibrous layer were prepared and enriched with FGF2-STAB® at concentrations of 0, 0.1, 1.0, and 10.0 μg ‧ cm-2. The performance of these dermal substitutes was tested in vivo on artificially formed skin defects in female swine. The outcomes were evaluated using cutometry at 3 and 6 months. In addition, visual appearance was assessed based on photos of the scars at 1-month, 3-month and 6-month follow-ups using Yeong scale and Visual Analog Scale. RESULTS: The dermal substitute was fully integrated into all defects and all wounds healed successfully. FGF2-STAB®-enriched matrices yielded better results in cutometry compared to scaffolds without FGF2. Visual evaluation at 1, 3, and 6 months follow-ups detected no significant differences among groups. The FGF2-STAB® effectiveness in improving the elasticity of scar tissues was confirmed in the swine model. This effect was independently observed in the scaffolds with nanofibres as well as in the scaffolds without nanofibres. CONCLUSION: The formation of scars with the best elasticity was exhibited by addition 1.0 μg ‧ cm-2of FGF2-STAB® into the scaffolds, although it had no significant effect on visual appearance at longer follow-ups. This study creates the basis for further translational studies of the developed product and its progression into the clinical phase of the research.
- MeSH
- chitosan * MeSH
- fibroblastový růstový faktor 2 * MeSH
- hojení ran účinky léků MeSH
- jizva hypertrofická MeSH
- kolagen MeSH
- kůže MeSH
- modely nemocí na zvířatech MeSH
- nanovlákna terapeutické užití MeSH
- popálení MeSH
- prasata MeSH
- pružnost * MeSH
- tkáňové podpůrné struktury MeSH
- umělá kůže * MeSH
- viskozita MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Shear viscosity of lipid membranes dictates how fast lipids, proteins, and other membrane constituents travel along the membrane and rotate around their principal axis, thus governing the rates of diffusion-limited reactions taking place at membranes. In this framework, the heterogeneity of biomembranes indicates that cells could regulate these rates via varying local viscosities. Unfortunately, experiments to probe membrane viscosity under various conditions are tedious and error prone. Molecular dynamics simulations provide an attractive alternative, especially given that recent theoretical developments enable the elimination of finite-size effects in simulations. Here, we use a variety of different equilibrium methods to extract the shear viscosities of lipid membranes from both coarse-grained and all-atom molecular dynamics simulations. We systematically probe the variables relevant for cellular membranes, namely, membrane protein crowding, cholesterol concentration, and the length and saturation level of lipid acyl chains, as well as temperature. Our results highlight that in their physiologically relevant ranges, protein concentration, cholesterol concentration, and temperature have significantly larger effects on membrane viscosity than lipid acyl chain length and unsaturation level. In particular, the crowding with proteins has a significant effect on the shear viscosity of lipid membranes and thus on the diffusion occurring in the membranes. Our work also provides the largest collection of membrane viscosity values from simulation to date, which can be used by the community to predict the diffusion coefficients or their trends via the Saffman-Delbrück description. Additionally, it is worth emphasizing that diffusion coefficients extracted from simulations exploiting periodic boundary conditions must be corrected for the finite-size effects prior to comparison with experiment, for which the present collection of viscosity values can readily be used. Finally, our thorough comparison to experiments suggests that there is room for improvement in the description of bilayer dynamics provided by the present force fields.
Hyaluronan (HA) is widely used for eye drops as lubricant to counteract dry eye disease. High and low molecular weight HA are currently used in ophthalmology. However, a large portion of the current literature on friction and lubrication addresses articular (joint) cartilage. Therefore, eye drops compositions based on HA and its derivatized forms are extensively characterized providing data on the tribological and mucoadhesive properties. The physiochemical properties are investigated in buffers used commonly in eye drops formulations. The tribological investigation reveals that amphiphilic HA-C12 decreases the friction coefficient. At the same time, the combination of trehalose/HA or HAC12 enhances up to eighty-fold the mucoadhesiveness. Thus, it is predicted a prolonged residence time on the surface of the eye. The incorporation of trehalose enhances the protection of human keratinocytes (HaCaT) cells, as demonstrated in an in-vitro cell-desiccation model. The presence of trehalose increases the friction coefficient. Medium molecular weight HA shows significantly lower friction coefficient than high molecular weight HA. This research represents a first, wide array of features of diverse HA forms for eye drops contributing to increase the knowledge of these preparations. The results here presented also provide valuable information for the design of highly performing HA-formulations addressing specific needs before preclinic.
- MeSH
- adhezivita MeSH
- buněčné linie keratinocytů HaCaT MeSH
- filtrace MeSH
- hlen účinky léků MeSH
- kyselina hyaluronová chemická syntéza chemie farmakologie MeSH
- lékové transportní systémy * MeSH
- lidé MeSH
- lubrikace * MeSH
- nefelometrie a turbidimetrie MeSH
- oči účinky léků MeSH
- oční roztoky farmakologie MeSH
- protonová magnetická rezonanční spektroskopie MeSH
- reologie MeSH
- sterilizace MeSH
- tření MeSH
- viskozita MeSH
- vysoušení MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A new method to estimate the selected viscoelastic parameters of foods using damped vibration analysis is presented for the evaluation of fruits and baked products. A flat disk is attached to the flat sample surface using a laser rangefinder that measures the sample thickness in advance, and it is locked by a trigger. Next, the trigger is released to allow the probe to press the sample through the force of gravity. The damped vibration of the probe caused by the deformation of the food is measured by monitoring the displacement of the probe via a linear encoder. The bulk modulus and viscosity are estimated using the fractional Zener model and mass. Young's modulus (E) is estimated independently by determining the maximum velocity of the probe using Hooke's law. Poisson's ratio (ν), and the shear modulus and viscosity are calculated by employing the estimated E and bulk modulus. The bulk modulus, bulk viscosity, shear modulus, shear viscosity, and E of apples were found to be higher than those of bananas. The bulk modulus, bulk viscosity, E, and shear modulus for white bread were lower than those for pound cake, but the ν values were higher, whereas those of sponge cake were intermediate. After drying the baked products for 1 day, most of the parameters of the samples increased, but the value of ν for white bread decreased. The proposed free-falling device estimated the four viscoelastic coefficients, Poisson's ratio, and Young's modulus of the food sample in less than 1 s.
- MeSH
- modul pružnosti MeSH
- pružnost * MeSH
- viskozita MeSH
- Publikační typ
- časopisecké články MeSH
Physiologically realistic results are the aim of every blood flow simulation. This is not different in aorto-coronary bypasses where the properties of the coronary circulation may significantly affect the relevance of the performed simulations. By considering three patient-specific bypass geometries, the present article focuses on two aspects of the coronary blood flow - its phasic flow pattern and its behaviour affected by blood rheology. For the phasic flow property, a multiscale modelling approach is chosen as a means to assess the ability of five different types of coronary boundary conditions (mean arterial pressure, Windkessel model and three lumped parameter models) to attain realistic coronary haemodynamics. From the analysed variants of boundary conditions, the best option in terms of physiological characteristics and its potential for use in patient-based simulations, is utilised to account for the effect of shear-dependent viscosity on the resulting haemodynamics and wall shear stress stimulation. Aside from the Newtonian model, the blood rheology is approximated by two non-Newtonian models in order to determine whether the choice of a viscosity model is important in simulations involving coronary circulation. A comprehensive analysis of obtained results demonstrated notable superiority of all lumped parameter models, especially in comparison to the constant outlet pressure, which regardless of bypass type gave overestimated and physiologically misleading results. In terms of rheology, it was noted that blood in undamaged coronary arteries behaves as a Newtonian fluid, whereas in vessels with atypical lumen geometry, such as that of anastomosis or stenosis, its shear-thinning behaviour should not be ignored.
Ophthalmic disorders are amid the most common pathologies worldwide. In this regard, hyaluronan (HA) has gained widespread use in eye surgeries and treatment of eye diseases. HA-based materials are well tolerated and show excellent biocompatibility. Therefore, HA is a sought-after component of ophthalmic formulations. However, several parameters have to be adjusted to reach an optimal performance and effectiveness. The complexity of HA properties represents a major challenge for biological and structural characterization. This review covers fundamental aspects and recent developments in HA ophthalmic research. Biological mechanisms underlying the health benefits of HA and their potential therapeutic applications are elaborated. Furthermore, current pharmacokinetic and safety studies are discussed. Noticeably, the benefits of chemical modification and processed HA forms are described to broaden the applications of this unique polysaccharide. The current research challenges and prospects are also outlined and discussed.
- MeSH
- glaukom farmakoterapie MeSH
- kyselina hyaluronová analogy a deriváty terapeutické užití MeSH
- lidé MeSH
- nosiče léků chemie MeSH
- oční nemoci farmakoterapie MeSH
- oční roztoky chemie MeSH
- protinádorové látky chemie metabolismus MeSH
- viskozita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The aim of this study was to prepare benzydamine hydrochloride loaded orodispersible films using modified semisolid extrusion 3D printing method. An innovative approach was developed where thin layer of drug loaded dispersion is printed and dried before printing of subsequent layers. Layer-by-layer drying as the in process step improves mechanical properties of films, uniformity of drug content and allows faster preparation of films in compounding settings due to shortening of drying time. Orodispersible films consisted of film forming maltodextrin, sorbitol as a plasticizer and hydroxyethylcellulose as a thickening agent. The height of the digital model showed excellent correlation with the disintegration time, weight, thickness and mechanical properties of prepared films. Drug content, predefined by volume of digital model and concentration of drug in print dispersion, showed excellent uniformity. The modified printing method shows great promise in a compounding production of personalized film dosage forms, and brings in possibilities such as one step preparation of films with compartmented drugs and incorporation of taste masking or release control layers.
This work concerns the chemical modification of medium molecular weight hyaluronan for ophthalmic applications. The synthesis of amphiphilic HA with dodecanoyl moities was carried out under mild aqueous conditions. Perfect control of the degree of substitution was obtained by varying the molar ratio of activated fatty acid used in the reaction feed. Moreover, the preparation of the derivatives was optimized to achieve the desired degree of substitution (DS = 9.0 ± 0.2 %). The prepared hyaluronan derivatives were water-soluble and exhibited self-associating properties (amphiphilicity). The structure of the prepared derivatives was elucidated by NMR spectroscopy, rheology, turbidity, SEC-MALLS, and gas chromatography (GC). The hydrophobic moieties increase the solution viscosity by physical crosslinking. Low concentration of HAC12 is needed to prepare highly viscous solutions with potential use for ophthalmic applications. Amphiphilic HA kept the biocompatibility of hyaluronan. The degree of substitution and Mw of the amphiphilic HA controls the sterilization by filtration. The protection against desiccation was tested using human keratinocytes (HaCaT) cells lines.
- MeSH
- buněčné linie keratinocytů HaCaT MeSH
- buňky NIH 3T3 MeSH
- hydrofobní a hydrofilní interakce MeSH
- kyselina hyaluronová chemie MeSH
- kyseliny laurové chemie MeSH
- lidé MeSH
- molekulová hmotnost MeSH
- muciny chemie MeSH
- myši MeSH
- povrchové napětí účinky léků MeSH
- příprava léků metody MeSH
- reologie metody MeSH
- syndromy suchého oka farmakoterapie MeSH
- viabilita buněk účinky léků MeSH
- viskozita účinky léků MeSH
- zvířata MeSH
- zvlhčující oční kapky chemie farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
