ABSTRACT
Cell spraying has become a feasible application method for cell therapy and tissue engineering approaches. Different devices have been used with varying success. Often, twin-fluid atomizers are used, which require a high gas velocity for optimal aerosolization characteristics. To decrease the amount and velocity of required air, a custom-made atomizer was designed based on the effervescent principle. Different designs were evaluated regarding spray characteristics and their influence on human adipose-derived mesenchymal stromal cells. The arithmetic mean diameters of the droplets were 15.4−33.5 µm with decreasing diameters for increasing gas-to-liquid ratios. The survival rate was >90% of the control for the lowest gas-to-liquid ratio. For higher ratios, cell survival decreased to approximately 50%. Further experiments were performed with the design, which had shown the highest survival rates. After seven days, no significant differences in metabolic activity were observed. The apoptosis rates were not influenced by aerosolization, while high gas-to-liquid ratios caused increased necrosis levels. Tri-lineage differentiation potential into adipocytes, chondrocytes, and osteoblasts was not negatively influenced by aerosolization. Thus, the effervescent aerosolization principle was proven suitable for cell applications requiring reduced amounts of supplied air. This is the first time an effervescent atomizer was used for cell processing.
ABSTRACT
Introduction: Bronchoscopic spraying has potential for the application of therapeutic drugs in distal regions of the lung by bypassing the upper airways. However, there is a lack of understanding about the underlying fluid transport phenomena that are responsible for the intrapulmonary propagation of applied liquid. Methods: By using a transparent airway model, this study provides first experimental insights into relevant transport phenomena of bronchoscopic spraying. Furthermore, the penetration depth of the application is quantitatively evaluated. Laser-induced fluorescence is used to analyze fluid propagation in the transparent channels. Potential influencing factors such as the positioning in different airways, application number, breathing pattern, and lung obstructions are varied within this study to determine their influence on liquid deposition. Findings: This study shows that the method of bronchoscopic spraying allows the application of liquid in distal regions of the airway model. The position of the bronchoscope is a key influencing factor in increasing the penetration depth. We found that fluid transport along the distal airways essentially occurs by the film and plug flow phenomenon during application, which is similar to the transport mechanisms during instillation. Liquid plugs in lower airways are responsible for the reorganization of liquid during proximal movements and thereby influence the penetration depth in subsequent applications.
Subject(s)
Lung , Trachea , Administration, Inhalation , FluorescenceABSTRACT
INTRODUCTION: Wall shear stress (WSS) is associated with the growth and rupture of an intracranial aneurysm. To reveal their underlying connections, many image-based computational fluid dynamics (CFD) studies have been conducted. However, the methodological validations using both in vivo medical imaging and in vitro optical flow measurements were rarely accompanied in such studies. METHODS: In the present study, we performed a comparative assessment on the hemodynamics of a patient-specific intracranial saccular aneurysm using in vivo 4D Flow MRI, in silico CFD, in vitro stereoscopic and tomographic particle imaging velocimetry (Stereo-PIV and Tomo-PIV) techniques. PIV experiments and CFD were conducted under steady state corresponding to the peak systole of 4D Flow MRI. RESULTS: The results showed that all modalities provided similar flow features and overall surface distribution of WSS. However, a large variation in the absolute WSS values was found. 4D Flow MRI estimated a 2- to 4-fold lower peak WSS (3.99 Pa) and a 1.6- to 2-fold lower mean WSS (0.94 Pa) than Tomo-PIV, Stereo-PIV, and CFD. Bland-Altman plots of WSS showed that the differences between PIV-/CFD-based WSS and 4D Flow MRI-based WSS increase with higher WSS magnitude. Such proportional trend was absent in the Bland-Altman comparison of velocity where the resolutions of PIV and CFD datasets were matched to 4D Flow MRI. We also found that because of superior resolution in the out-of-plane direction, WSS estimation by Tomo-PIV was higher than Stereo-PIV. CONCLUSIONS: Our results indicated that the differences in spatial resolution could be the main contributor to the discrepancies between each modality. The findings of this study suggest that with current techniques, care should be taken when using absolute WSS values to perform a quantitative risk analysis of aneurysm rupture.