The performance of porous scaffolds for tissue engineering (TE) applications is evaluated, in general, in terms of porosity, pore size and distribution, and pore tortuosity. These descriptors are often confounding when they are applied to characterize transport phenomena within porous scaffolds. On the contrary, permeability is a more effective parameter in (1) estimating mass and species transport through the scaffold and (2) describing its topological features, thus allowing a better evaluation of the overall scaffold performance. However, the evaluation of TE scaffold permeability suffers of a lack of uniformity and standards in measurement and testing procedures which makes the comparison of results obtained in different laboratories unfeasible. In this review paper we summarize the most important features influencing TE scaffold permeability, linking them to the theoretical background. An overview of methods applied for TE scaffold permeability evaluation is given, presenting experimental test benches and computational methods applied (1) to integrate experimental measurements and (2) to support the TE scaffold design process. Both experimental and computational limitations in the permeability evaluation process are also discussed.
Cardiovascular disease is the leading cause of morbidity and mortality in the Western World. The inability of fully differentiated, load-bearing cardiovascular tissues to in vivo regenerate and the limitations of the current treatment therapies greatly motivate the efforts of cardiovascular tissue engineering to become an effective clinical strategy for injured heart and vessels. For the effective production of organized and functional cardiovascular engineered constructs in vitro, a suitable dynamic environment is essential, and can be achieved and maintained within bioreactors. Bioreactors are technological devices that, while monitoring and controlling the culture environment and stimulating the construct, attempt to mimic the physiological milieu. In this study, a review of the current state of the art of bioreactor solutions for cardiovascular tissue engineering is presented, with emphasis on bioreactors and biophysical stimuli adopted for investigating the mechanisms influencing cardiovascular tissue development, and for eventually generating suitable cardiovascular tissue replacements.
This paper reports a new low-cost passive microfluidic mixer design, based on a replication of identical mixing units composed of microchannels with variable curvature (clothoid) geometry. The micromixer presents a compact and modular architecture that can be easily fabricated using a simple and reliable fabrication process. The particular clothoid-based geometry enhances the mixing by inducing transversal secondary flows and recirculation effects. The role of the relevant fluid mechanics mechanisms promoting the mixing in this geometry were analysed using computational fluid dynamics (CFD) for Reynolds numbers ranging from 1 to 110. A measure of mixing potency was quantitatively evaluated by calculating mixing efficiency, while a measure of particle dispersion was assessed through the lacunarity index. The results show that the secondary flow arrangement and recirculation effects are able to provide a mixing efficiency equal to 80 % at Reynolds number above 70. In addition, the analysis of particles distribution promotes the lacunarity as powerful tool to quantify the dispersion of fluid particles and, in turn, the overall mixing. On fabricated micromixer prototypes the microscopic-Laser-Induced-Fluorescence (μLIF) technique was applied to characterize mixing. The experimental results confirmed the mixing potency of the microdevice.
An accurate intrinsic permeability measurement system has been designed and realized in order to quantify the inter-pore connectivity structure of tissue-engineering scaffolds by using a single (pressure) transducer. The proposed method uses a slow alternating airflow as a fluid medium and allows at the same time a simple and accurate measurement procedure. The intrinsic permeability is determined in the linear Darcy's region, and deviation from linearity due to inertial losses is also quantified. The structural parameters of a scaffold, such as effective porosity, tortuosity and effective length of cylindrical pores, are estimated using the classical Ergun's equation recently modified by Wu et al. From this relation, it is possible to achieve a well-defined range of data and associated uncertainties for characterizing the structure/architecture of tissue-engineering scaffolds. This quantitative analysis is of paramount importance in tissue engineering, where scaffold topological features are strongly related to their biological performance.
The aim of the present study is to characterize the microstructure of composite scaffolds for bone tissue regeneration containing different ratios of chitosan/gelatin blend and bioactive glasses. Starting from realistic 3D models of the scaffolds reconstructed from micro-CT images, the level of heterogeneity of scaffold architecture is evaluated performing a lacunarity analysis. The results demonstrate that the presence of the bioactive glass component affects not only macroscopic features such as porosity, but mainly scaffold microarchitecture giving rise to structural heterogeneity, which could have an impact on the local cell-scaffold interaction and scaffold performances. The adopted approach allows to investigate the scale-dependent pore distribution within the scaffold and the related structural heterogeneity features, providing a comprehensive characterization of the scaffold texture.
In tissue engineering (TE), scaffolds are widely used to provide a suitable and native-like environment for cell growth, organization, and proliferation. Microstructure of TE scaffolds is fundamental to the cell attachment and in-depth penetration, in conjunction with biological factors as cell seeding and nutrients supply. In particular, several studies have established that an adequate transport of nutrient through the scaffold is fundamental for culturing cells [1]. Hence, the easiness at which fluids/species move through the scaffold and friction forces exherted from fluid motion, have a marked impact in TE processes [2]. Mass transport through scaffolds is a phenomenon that can be described at different scales, the molecular level (nanoscale), the single-pore dimension level (microscale) and the whole-sample level (macroscale). In this work we present a virtual test bench where realistic 3D models of porous TE scaffolds are reconstructed from micro-CT images and the transport phenomena through them is simulated in silico by applying the Lattice Boltzmann Method (LBM). The final aim is to create an effective in silico tool suitable to study and optimize transport phenomena of porous scaffolds. The application of the LBM is justified by its versatility in simulating flows in irregular porous media (i.e. simplicity of handling complex boundaries) and in providing insights into transport properties such as permeability [3–4] and physical quantities as the shear stress, which are barely achievable experimentally [2]. Here, the virtual tool is applied to evaluate the performance of three biomimetic bioactive glass/polymer composite porous scaffolds for bone tissue regeneration with well-known mechanical and chemical properties, but never characterized in terms of transport phenomena. The in silico results are macroscopically validated in terms of permeability (kC) by comparison with experimental permeability (kE) measurements obtained by means of a dedicated test bench, very recently proposed for the characterization of porous media [5].
Our previous study of interaction between low intensity radiation at 53.37GHz and cell-size system - such as giant vesicles - indicated that a vectorial movement of vesicles was induced. This effect among others, i.e. elongation, induced diffusion of fluorescent dye di-8-ANEPPS, and increased attractions between vesicles was attributed to the action of the field on charged and dipolar residues located at the membrane-water interface. In an attempt to improve the understanding on how millimeter wave radiation (MMW) can induce this movement we report here a real time evaluation of changes induced on the movement of giant vesicles. Direct optical observations of vesicles subjected to irradiation enabled the monitoring in real time of the response of vesicles. Changes of the direction of vesicle movement are demonstrated, which occur only during irradiation with a "switch on" of the effect. This MMW-induced effect was observed at a larger extent on giant vesicles prepared with negatively charged phospholipids. The monitoring of induced-by-irradiation temperature variation and numerical dosimetry indicate that the observed effects in vesicle movement cannot be attributed to local heating.
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