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Institute
- IfB - Institut für Bioengineering (408) (remove)
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.
Exposure to prolonged periods in microgravity is associated with deconditioning of the musculoskeletal system due to chronic changes in mechanical stimulation. Given astronauts will operate on the Lunar surface for extended periods of time, it is critical to quantify both external (e.g., ground reaction forces) and internal (e.g., joint reaction forces) loads of relevant movements performed during Lunar missions. Such knowledge is key to predict musculoskeletal deconditioning and determine appropriate exercise countermeasures associated with extended exposure to hypogravity.
Background
Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians.
Methods
In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204).
Measurements and main results
PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters.
Conclusion
Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.
This study evaluates neuromechanical control and muscle-tendon interaction during energy storage and dissipation tasks in hypergravity. During parabolic flights, while 17 subjects performed drop jumps (DJs) and drop landings (DLs), electromyography (EMG) of the lower limb muscles was combined with in vivo fascicle dynamics of the gastrocnemius medialis, two-dimensional (2D) kinematics, and kinetics to measure and analyze changes in energy management. Comparisons were made between movement modalities executed in hypergravity (1.8 G) and gravity on ground (1 G). In 1.8 G, ankle dorsiflexion, knee joint flexion, and vertical center of mass (COM) displacement are lower in DJs than in DLs; within each movement modality, joint flexion amplitudes and COM displacement demonstrate higher values in 1.8 G than in 1 G. Concomitantly, negative peak ankle joint power, vertical ground reaction forces, and leg stiffness are similar between both movement modalities (1.8 G). In DJs, EMG activity in 1.8 G is lower during the COM deceleration phase than in 1 G, thus impairing quasi-isometric fascicle behavior. In DLs, EMG activity before and during the COM deceleration phase is higher, and fascicles are stretched less in 1.8 G than in 1 G. Compared with the situation in 1 G, highly task-specific neuromuscular activity is diminished in 1.8 G, resulting in fascicle lengthening in both movement modalities. Specifically, in DJs, a high magnitude of neuromuscular activity is impaired, resulting in altered energy storage. In contrast, in DLs, linear stiffening of the system due to higher neuromuscular activity combined with lower fascicle stretch enhances the buffering function of the tendon, and thus the capacity to safely dissipate energy.
It has been shown that muscle fascicle curvature increases with increasing contraction level and decreasing muscle–tendon complex length. The analyses were done with limited examination windows concerning contraction level, muscle–tendon complex length, and/or intramuscular position of ultrasound imaging. With this study we aimed to investigate the correlation between fascicle arching and contraction, muscle–tendon complex length and their associated architectural parameters in gastrocnemius muscles to develop hypotheses concerning the fundamental mechanism of fascicle curving. Twelve participants were tested in five different positions (90°/105°*, 90°/90°*, 135°/90°*, 170°/90°*, and 170°/75°*; *knee/ankle angle). They performed isometric contractions at four different contraction levels (5%, 25%, 50%, and 75% of maximum voluntary contraction) in each position. Panoramic ultrasound images of gastrocnemius muscles were collected at rest and during constant contraction. Aponeuroses and fascicles were tracked in all ultrasound images and the parameters fascicle curvature, muscle–tendon complex strain, contraction level, pennation angle, fascicle length, fascicle strain, intramuscular position, sex and age group were analyzed by linear mixed effect models. Mean fascicle curvature of the medial gastrocnemius increased with contraction level (+5 m−1 from 0% to 100%; p = 0.006). Muscle–tendon complex length had no significant impact on mean fascicle curvature. Mean pennation angle (2.2 m−1 per 10°; p < 0.001), inverse mean fascicle length (20 m−1 per cm−1; p = 0.003), and mean fascicle strain (−0.07 m−1 per +10%; p = 0.004) correlated with mean fascicle curvature. Evidence has also been found for intermuscular, intramuscular, and sex-specific intramuscular differences of fascicle curving. Pennation angle and the inverse fascicle length show the highest predictive capacities for fascicle curving. Due to the strong correlations between pennation angle and fascicle curvature and the intramuscular pattern of curving we suggest for future studies to examine correlations between fascicle curvature and intramuscular fluid pressure.
Based on the European Space Agency (ESA) Science in Space Environment (SciSpacE) community White Paper “Human Physiology – Musculoskeletal system”, this perspective highlights unmet needs and suggests new avenues for future studies in musculoskeletal research to enable crewed exploration missions. The musculoskeletal system is essential for sustaining physical function and energy metabolism, and the maintenance of health during exploration missions, and consequently mission success, will be tightly linked to musculoskeletal function. Data collection from current space missions from pre-, during-, and post-flight periods would provide important information to understand and ultimately offset musculoskeletal alterations during long-term spaceflight. In addition, understanding the kinetics of the different components of the musculoskeletal system in parallel with a detailed description of the molecular mechanisms driving these alterations appears to be the best approach to address potential musculoskeletal problems that future exploratory-mission crew will face. These research efforts should be accompanied by technical advances in molecular and phenotypic monitoring tools to provide in-flight real-time feedback.
Bacterial cellulose (BC) is a biopolymer produced by different microorganisms, but in biotechnological practice, Komagataeibacter xylinus is used. The micro- and nanofibrillar structure of BC, which forms many different-sized pores, creates prerequisites for the introduction of other polymers into it, including those synthesized by other microorganisms. The study aims to develop a cocultivation system of BC and prebiotic producers to obtain BC-based composite material with prebiotic activity. In this study, pullulan (PUL) was found to stimulate the growth of the probiotic strain Lactobacillus rhamnosus GG better than the other microbial polysaccharides gellan and xanthan. BC/PUL biocomposite with prebiotic properties was obtained by cocultivation of Komagataeibacter xylinus and Aureobasidium pullulans, BC and PUL producers respectively, on molasses medium. The inclusion of PUL in BC is proved gravimetrically by scanning electron microscopy and by Fourier transformed infrared spectroscopy. Cocultivation demonstrated a composite effect on the aggregation and binding of BC fibers, which led to a significant improvement in mechanical properties. The developed approach for “grafting” of prebiotic activity on BC allows preparation of environmentally friendly composites of better quality.
Humic substances (HS), as important environmental components, are essential to soil health and agricultural sustainability. The usage of low-rank coal (LRC) for energy generation has declined considerably due to the growing popularity of renewable energy sources and gas. However, their potential as soil amendment aimed to maintain soil quality and productivity deserves more recognition. LRC, a highly heterogeneous material in nature, contains large quantities of HS and may effectively help to restore the physicochemical, biological, and ecological functionality of soil. Multiple emerging studies support the view that LRC and its derivatives can positively impact the soil microclimate, nutrient status, and organic matter turnover. Moreover, the phytotoxic effects of some pollutants can be reduced by subsequent LRC application. Broad geographical availability, relatively low cost, and good technical applicability of LRC offer the advantage of easy fulfilling soil amendment and conditioner requirements worldwide. This review analyzes and emphasizes the potential of LRC and its numerous forms/combinations for soil amelioration and crop production. A great benefit would be a systematic investment strategy implicating safe utilization and long-term application of LRC for sustainable agricultural production.
Objective
Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels.
Methods
152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions.
Results
In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained.
Conclusion
This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention.
It was generally believed that coal sources are not favorable as live-in habitats for microorganisms due to their recalcitrant chemical nature and negligible decomposition. However, accumulating evidence has revealed the presence of diverse microbial groups in coal environments and their significant metabolic role in coal biogeochemical dynamics and ecosystem functioning. The high oxygen content, organic fractions, and lignin-like structures of lower-rank coals may provide effective means for microbial attack, still representing a greatly unexplored frontier in microbiology. Coal degradation/conversion technology by native bacterial and fungal species has great potential in agricultural development, chemical industry production, and environmental rehabilitation. Furthermore, native microalgal species can offer a sustainable energy source and an excellent bioremediation strategy applicable to coal spill/seam waters. Additionally, the measures of the fate of the microbial community would serve as an indicator of restoration progress on post-coal-mining sites. This review puts forward a comprehensive vision of coal biodegradation and bioprocessing by microorganisms native to coal environments for determining their biotechnological potential and possible applications.
FEM shakedown analysis of structures under random strength with chance constrained programming
(2022)
Direct methods, comprising limit and shakedown analysis, are a branch of computational mechanics. They play a significant role in mechanical and civil engineering design. The concept of direct methods aims to determine the ultimate load carrying capacity of structures beyond the elastic range. In practical problems, the direct methods lead to nonlinear convex optimization problems with a large number of variables and constraints. If strength and loading are random quantities, the shakedown analysis can be formulated as stochastic programming problem. In this paper, a method called chance constrained programming is presented, which is an effective method of stochastic programming to solve shakedown analysis problems under random conditions of strength. In this study, the loading is deterministic, and the strength is a normally or lognormally distributed variable.
Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.
Edge-based and face-based smoothed finite element methods (ES-FEM and FS-FEM, respectively) are modified versions of the finite element method allowing to achieve more accurate results and to reduce sensitivity to mesh distortion, at least for linear elements. These properties make the two methods very attractive. However, their implementation in a standard finite element code is nontrivial because it requires heavy and extensive modifications to the code architecture. In this article, we present an element-based formulation of ES-FEM and FS-FEM methods allowing to implement the two methods in a standard finite element code with no modifications to its architecture. Moreover, the element-based formulation permits to easily manage any type of element, especially in 3D models where, to the best of the authors' knowledge, only tetrahedral elements are used in FS-FEM applications found in the literature. Shape functions for non-simplex 3D elements are proposed in order to apply FS-FEM to any standard finite element.
The mechanical behavior of the large intestine beyond the ultimate stress has never been investigated. Stretching beyond the ultimate stress may drastically impair the tissue microstructure, which consequently weakens its healthy state functions of absorption, temporary storage, and transportation for defecation. Due to closely similar microstructure and function with humans, biaxial tensile experiments on the porcine large intestine have been performed in this study. In this paper, we report hyperelastic characterization of the large intestine based on experiments in 102 specimens. We also report the theoretical analysis of the experimental results, including an exponential damage evolution function. The fracture energies and the threshold stresses are set as damage material parameters for the longitudinal muscular, the circumferential muscular and the submucosal collagenous layers. A biaxial tensile simulation of a linear brick element has been performed to validate the applicability of the estimated material parameters. The model successfully simulates the biomechanical response of the large intestine under physiological and non-physiological loads.
Biocompatibility, flexibility and durability make polydimethylsiloxane (PDMS) membranes top candidates in biomedical applications. CellDrum technology uses large area, <10 µm thin membranes as mechanical stress sensors of thin cell layers. For this to be successful, the properties (thickness, temperature, dust, wrinkles, etc.) must be precisely controlled. The following parameters of membrane fabrication by means of the Floating-on-Water (FoW) method were investigated: (1) PDMS volume, (2) ambient temperature, (3) membrane deflection and (4) membrane mechanical compliance. Significant differences were found between all PDMS volumes and thicknesses tested (p < 0.01). They also differed from the calculated values. At room temperatures between 22 and 26 °C, significant differences in average thickness values were found, as well as a continuous decrease in thicknesses within a 4 °C temperature elevation. No correlation was found between the membrane thickness groups (between 3–4 µm) in terms of deflection and compliance. We successfully present a fabrication method for thin bio-functionalized membranes in conjunction with a four-step quality management system. The results highlight the importance of tight regulation of production parameters through quality control. The use of membranes described here could also become the basis for material testing on thin, viscous layers such as polymers, dyes and adhesives, which goes far beyond biological applications.
Orthodontic treatments are concomitant with mechanical forces and thereby cause teeth movements. The applied forces are transmitted to the tooth root and the periodontal ligaments which is compressed on one side and tensed up on the other side. Indeed, strong forces can lead to tooth root resorption and the crown-to-tooth ratio is reduced with the potential for significant clinical impact. The cementum, which covers the tooth root, is a thin mineralized tissue of the periodontium that connects the periodontal ligament with the tooth and is build up by cementoblasts. The impact of tension and compression on these cells is investigated in several in vivo and in vitro studies demonstrating differences in protein expression and signaling pathways. In summary, osteogenic marker changes indicate that cyclic tensile forces support whereas static tension inhibits cementogenesis. Furthermore, cementogenesis experiences the same protein expression changes in static conditions as static tension, but cyclic compression leads to the exact opposite of cyclic tension. Consistent with marker expression changes, the singaling pathways of Wnt/ß-catenin and RANKL/OPG show that tissue compression leads to cementum degradation and tension forces to cementogenesis. However, the cementum, and in particular its cementoblasts, remain a research area which should be explored in more detail to understand the underlying mechanism of bone resorption and remodeling after orthodontic treatments.
Introduction
In regard of surgical training, the reproducible simulation of life-like proximal humerus fractures in human cadaveric specimens is desirable. The aim of the present study was to develop a technique that allows simulation of realistic proximal humerus fractures and to analyse the influence of rotator cuff preload on the generated lesions in regards of fracture configuration.
Materials and methods
Ten cadaveric specimens (6 left, 4 right) were fractured using a custom-made drop-test bench, in two groups. Five specimens were fractured without rotator cuff preload, while the other five were fractured with the tendons of the rotator cuff preloaded with 2 kg each. The humeral shaft and the shortened scapula were potted. The humerus was positioned at 90° of abduction and 10° of internal rotation to simulate a fall on the elevated arm. In two specimens of each group, the emergence of the fractures was documented with high-speed video imaging. Pre-fracture radiographs were taken to evaluate the deltoid-tuberosity index as a measure of bone density. Post-fracture X-rays and CT scans were performed to define the exact fracture configurations. Neer’s classification was used to analyse the fractures.
Results
In all ten cadaveric specimens life-like proximal humerus fractures were achieved. Two III-part and three IV-part fractures resulted in each group. The preloading of the rotator cuff muscles had no further influence on the fracture configuration. High-speed videos of the fracture simulation revealed identical fracture mechanisms for both groups. We observed a two-step fracture mechanism, with initial impaction of the head segment against the glenoid followed by fracturing of the head and the tuberosities and then with further impaction of the shaft against the acromion, which lead to separation of the tuberosities.
Conclusion
A high energetic axial impulse can reliably induce realistic proximal humerus fractures in cadaveric specimens. The preload of the rotator cuff muscles had no influence on initial fracture configuration. Therefore, fracture simulation in the proximal humerus is less elaborate. Using the presented technique, pre-fractured specimens are available for real-life surgical education.
Introduction: In peripheral percutaneous (VA) extracorporeal membrane oxygenation (ECMO) procedures the femoral arteries perfusion route has inherent disadvantages regarding poor upper body perfusion due to watershed. With the advent of new long flexible cannulas an advancement of the tip up to the ascending aorta has become feasible. To investigate the impact of such long endoluminal cannulas on upper body perfusion, a Computational Fluid Dynamics (CFD) study was performed considering different support levels and three cannula positions.
Methods: An idealized literature-based- and a real patient proximal aortic geometry including an endoluminal cannula were constructed. The blood flow was considered continuous. Oxygen saturation was set to 80% for the blood coming from the heart and to 100% for the blood leaving the cannula. 50% and 90% venoarterial support levels from the total blood flow rate of 6 l/min were investigated for three different positions of the cannula in the aortic arch.
Results: For both geometries, the placement of the cannula in the ascending aorta led to a superior oxygenation of all aortic blood vessels except for the left coronary artery. Cannula placements at the aortic arch and descending aorta could support supra-aortic arteries, but not the coronary arteries. All positions were able to support all branches with saturated blood at 90% flow volume.
Conclusions: In accordance with clinical observations CFD analysis reveals, that retrograde advancement of a long endoluminal cannula can considerably improve the oxygenation of the upper body and lead to oxygen saturation distributions similar to those of a central cannulation.
Searching optimal interplanetary trajectories for low-thrust spacecraft is usually a difficult and time-consuming task that involves much experience and expert knowledge in astrodynamics and optimal control theory. This is because the convergence behavior of traditional local optimizers, which are based on numerical optimal control methods, depends on an adequate initial guess, which is often hard to find, especially for very-low-thrust trajectories that necessitate many revolutions around the sun. The obtained solutions are typically close to the initial guess that is rarely close to the (unknown) global optimum. Within this paper, trajectory optimization problems are attacked from the perspective of artificial intelligence and machine learning. Inspired by natural archetypes, a smart global method for low-thrust trajectory optimization is proposed that fuses artificial neural networks and evolutionary algorithms into so-called evolutionary neurocontrollers. This novel method runs without an initial guess and does not require the attendance of an expert in astrodynamics and optimal control theory. This paper details how evolutionary neurocontrol works and how it could be implemented. The performance of the method is assessed for three different interplanetary missions with a thrust to mass ratio <0.15mN/kg (solar sail and nuclear electric).
Contractile behavior of the gastrocnemius medialis muscle during running in simulated hypogravity
(2021)
Vigorous exercise countermeasures in microgravity can largely attenuate muscular degeneration, albeit the extent of applied loading is key for the extent of muscle wasting. Running on the International Space Station is usually performed with maximum loads of 70% body weight (0.7 g). However, it has not been investigated how the reduced musculoskeletal loading affects muscle and series elastic element dynamics, and thereby force and power generation. Therefore, this study examined the effects of running on the vertical treadmill facility, a ground-based analog, at simulated 0.7 g on gastrocnemius medialis contractile behavior. The results reveal that fascicle−series elastic element behavior differs between simulated hypogravity and 1 g running. Whilst shorter peak series elastic element lengths at simulated 0.7 g appear to be the result of lower muscular and gravitational forces acting on it, increased fascicle lengths and decreased velocities could not be anticipated, but may inform the development of optimized running training in hypogravity. However, whether the alterations in contractile behavior precipitate musculoskeletal degeneration warrants further study.