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The human nose serves as the primary gateway for air entering the respiratory system and plays a vital role in breathing. Nasal breathing difficulties are a significant health concern, leading to substantial healthcare costs for patients. Understanding nasal airflow dynamics is crucial for comprehending respiratory mechanisms. This article presents a detailed study using tomo-Particle Image Velocimetry (PIV) to investigate nasal airflow dynamics while addressing its accuracy. Embedded in the OpenNose project, the work described aims to provide a validation basis for different numerical approaches to upper airway flow. The study includes the manufacturing of a transparent silicone model based on a clinical CT scan, refractive index matching to minimize optical distortions, and precise flow rate adjustments based on physiological breathing cycles. This method allows for spatial high-resolution investigations in different regions of interest within the nasopharynx during various phases of the breathing cycle. The results demonstrate the accuracy of the investigations, enabling detailed analysis of flow structures and gradients. This spatial high-resolution tomo-PIV approach provides valuable insights into the complex flow phenomena occurring during the physiological breathing cycle in the nasopharynx. The study's findings contribute to advancements in non-free-of-sight experimental flow investigation of complex cavities under nearly realistic conditions. Furthermore, reliable and accurate experimental data is crucial for properly validating numerical approaches that compute this patient-specific flow for clinical purposes.
Early motion therapy plays an important role for effective long-term healing of joint injuries. In many cases, conventional dynamic orthoses fail to address the intricate movement possibilities of the underlying joints, limited by their simplistic joint representations, often represented by revolute joints, enabling rotations by only one axis. In this paper, a two-dimensional compliant tensegrity joint for use in biomedical applications is investigated. It consists of two compressed members and five compliant tensioned members. Relative movement possibilities are realized by the intrinsic compliance of the structure. In the development of these systems, the first step is the determination of the static stable equilibrium. This analysis is conducted in this paper by considering the potential energy approach or by using the geometric nonlinear finite element method. The mechanical behavior of the structure is assessed with a specific emphasis on its mechanical compliance. The primary objective of this study is the investigation of the influence of structural parameters on the overall stiffness and movability of the structure. The results underscore the significant effect of member parameters on the stiffness and movability of the compliant tensegrity joint, particularly under varying load magnitudes. These findings provide insights for optimizing the joint’s performance, contributing to its potential application in advanced orthotic and exoskeleton devices.
BACKGROUND: Thrombosis remains a critical complication during venovenous extracorporeal membrane oxygenation (VV ECMO). The involvement of neutrophil extracellular traps (NETs) in thrombogenesis has to be discussed. The aim was to verify NETs in the form of cell-free DNA (cfDNA) in the plasma of patients during ECMO.
METHODS: A fluorescent DNA-binding dye (QuantifFluor®, Promega) was used to detect cell-free DNA in plasma samples. cfDNA concentrations from volunteers (n = 21) and patients (n = 9) were compared and correlated with clinical/technical data before/during support, ECMO end and time of a system exchange.
RESULTS: Before ECMO, patients with a median (IQR) age of 59 (51/63) years, SOFA score of 11 (10/15), and ECMO run time of 9.0 (7.0/19.5) days presented significantly higher levels of cfDNA compared to volunteers (6.4 (5.8/7.9) ng/μL vs. 5.9 (5.4/6.3) ng/μL; p = 0.044). Within 2 days after ECMO start, cfDNA, inflammatory, and hemolysis parameters remained unchanged, while platelets decreased (p = 0.005). After ECMO removal at the end of therapy, cfDNA, inflammation, and coagulation data (except antithrombin III) remained unchanged. The renewal of a system resulted in known alterations in fibrinogen, d-dimers, and platelets, while cfDNA remained unchanged.
CONCLUSION: Detection of cfDNA in plasma of ECMO patients was not an indicator of acute and circuit-induced thrombogenesis.
Aufgrund der steigenden Lebenserwartung und dem damit einhergehenden demographischen Wandel wird der Bedarf an Rehabilitations-Behandlungen in absehbarer Zukunft stark ansteigen. Ein Beispiel für diesen Trend ist die physiotherapeutische Behandlung nach Erhalt einer Knie-Totalendoprothese (Knie-TEP). So gehen Modellrechnungen basierend auf dem Bevölkerungswachstum und der bisherigen Prävalenz von Knie-TEPs davon aus, dass die Anzahl an durchgeführten Eingriffen in einkommensstarken Ländern wie Deutschland weiter zunehmen wird. Weiterhin stoßen traditionelle Rehabilitationsverfahren, gerade in strukturschwachen Regionen, schon heute an ihre Grenzen. Deutlich zu sehen war das während den Hochphasen der aktuellen Covid-19-Pandemie, als der Kontakt zwischen Therapeut*in und Patient*in flächendeckend eingeschränkt war. Eine erhöhte Nachfrage nach neuartigen Reha-Angeboten ist die logische Konsequenz. Innovative Konzepte sind daher dringend notwendig, um die daraus resultierenden technischen, sozialen und ökonomischen Herausforderungen zu bewältigen.
BACKGROUND:
Tracheobronchial mucus plays a crucial role in pulmonary function by providing protection against inhaled pathogens. Due to its composition of water, mucins, and other biomolecules, it has a complex viscoelastic rheological behavior. This interplay of both viscous and elastic properties has not been fully described yet. In this study, we characterize the rheology of human mucus using oscillatory and transient tests. Based on the transient tests, we describe the material behavior of mucus under stress and strain loading by mathematical models.
METHODS:
Mucus samples were collected from clinically used endotracheal tubes. For rheological characterization, oscillatory amplitude-sweep and frequency-sweep tests, and transient creep-recovery and stress-relaxation tests were performed. The results of the transient test were approximated using the Burgers model, the Weibull distribution, and the six-element Maxwell model. The three-dimensional microstructure of the tracheobronchial mucus was visualized using scanning electron microscope imaging.
RESULTS:
Amplitude-sweep tests showed storage moduli ranging from 0.1 Pa to 10000 Pa and a median critical strain of 4 %. In frequency-sweep tests, storage and loss moduli increased with frequency, with the median of the storage modulus ranging from 10 Pa to 30 Pa, and the median of the loss modulus from 5 Pa to 14 Pa. The Burgers model approximates the viscoelastic behavior of tracheobronchial mucus during a constant load of stress appropriately (R2 of 0.99), and the Weibull distribution is suitable to predict the recovery of the sample after the removal of this stress (R2 of 0.99). The approximation of the stress-relaxation test data by a six-element Maxwell model shows a larger fit error (R2 of 0.91).
CONCLUSIONS:
This study provides a detailed description of all process steps of characterizing the rheology of tracheobronchial mucus, including sample collection, microstructure visualization, and rheological investigation. Based on this characterization, we provide mathematical models of the rheological behavior of tracheobronchial mucus. These can now be used to simulate mucus flow in the respiratory system through numerical approaches.
Für Fußballer:innen stellen muskuläre Verletzungen der unteren Extremitäten ein großes Problem dar. Ein Beispiel hierfür liefert die Nationalmannschaftsstürmerin Alexandra Popp, die aufgrund muskulärer Probleme das EM-Finale 2022 in Wembley kurzfristig verpasste. Oftmals stehen gerade hohe Anspannungssituationen in zeitlichem Zusammenhang mit Verletzungen, der Einfluss der psychischen Beanspruchung auf die biomechanischen Belastungen wird jedoch meist nur wenig beachtet.
To avoid dislocation of the shoulder joint after reverse total shoulder arthroplasty, it is important to achieve sufficient shoulder stability when placing the implant components during surgery. One parameter for assessing shoulder stability can be shoulder stiffness. The aim of this research was to develop a temporary reverse shoulder implant prototype that would allow intraoperative measurement of shoulder stiffness while varying the position of the implant components. Joint angle and torque measurement techniques were developed to determine shoulder stiffness. Hall sensors were used to measure the joint angles by converting the magnetic flux densities into angles. The accuracy of the joint angle measurements was tested using a test bench. Torques were determined by using thin-film pressure sensors. Various mechanical mechanisms for variable positioning of the implant components were integrated into the prototype. The results of the joint angle measurements showed measurement errors of less than 5° in a deflection range of ±15° adduction/abduction combined with ±45° flexion/extension. The proposed design provides a first approach for intra-operative assessment of shoulder stiffness. The findings can be used as a technological basis for further developments.
In Vitro Analysis of Human Cartilage Infiltrated by Hydrogels and Hydrogel-Encapsulated Chondrocytes
(2023)
Osteoarthritis (OA) is a degenerative joint disease causing loss of articular cartilage and structural damage in all joint tissues. Given the limited regenerative capacity of articular cartilage, methods to support the native structural properties of articular cartilage are highly anticipated. The aim of this study was to infiltrate zwitterionic monomer solutions into human OA-cartilage explants to replace lost proteoglycans. The study included polymerization and deposition of methacryloyloxyethyl-phosphorylcholine- and a novel sulfobetaine-methacrylate-based monomer solution within ex vivo human OA-cartilage explants and the encapsulation of isolated chondrocytes within hydrogels and the corresponding effects on chondrocyte viability. The results demonstrated that zwitterionic cartilage–hydrogel networks are formed by infiltration. In general, cytotoxic effects of the monomer solutions were observed, as was a time-dependent infiltration behavior into the tissue accompanied by increasing cell death and penetration depth. The successful deposition of zwitterionic hydrogels within OA cartilage identifies the infiltration method as a potential future therapeutic option for the repair/replacement of OA-cartilage extracellular suprastructure. Due to the toxic effects of the monomer solutions, the focus should be on sealing the OA-cartilage surface, instead of complete infiltration. An alternative treatment option for focal cartilage defects could be the usage of monomer solutions, especially the novel generated sulfobetaine-methacrylate-based monomer solution, as bionic for cell-based 3D bioprintable hydrogels.
Surgical Smoke is generated during the cauterization of tissue with high-frequency (HF) devices and consists of 95% water vapor and 5% cellular debris. When the coagulation tweezers, which are supplied with HF voltage by the HF device, touch tissue, the electric circuit is closed, and smoke is generated by the heat. In-vivo investigations are performed during tracheotomies where surgical smoke is produced during coagulation of tissue. Furthermore, in-vitro parametric studies to investigate the particle number and size distribution and the spatial distribution of surgical smoke with laser light sheet technique are conducted. With higher power of the HF device, the particles generated are larger in size and the total number of particles generated is also higher. Adding artificial saliva to the tissue shows even higher particle counts. The study by laser light sheet also confirms this. The resulting characteristic size distribution, which may include viruses and bacterial components, confirms considering the risk arising from surgical smoke. Furthermore, the experiments will provide the database for further numerical investigations.
High Spatial Resolution Tomo-PIV of the Trachea Focussing on the Physiological Breathing Cycle
(2023)
Investigations of complex patient-specific flow in the nasopharynx requires high resolution numerical calculations validated by reliable experiments. When building the validation base and the benchmark of computational fluid dynamics, an experimental setup of the nasal airways was developed. The applied optical measurement technique of tomo-PIV supplies information on the governing flow field in three dimensions.
This paper presents tomo-PIV measurements of the highly complex patient-specific geometry of the human trachea. A computertomographic scan of a person’s head builds the basis of the experimental silicone model of the nasal airways. An optimised approach for precise refractive index matching avoids optical distortions even in highly complex non-free-of-sight 3D geometries. A linear-motor-driven pump generates breathing scenarios, based on measured breathing cycles. Adjusting of the CCD cameras‘ double-frame-rate PIV-Δt enables the detailed analysis of flow structures during different cycle phases. Merging regions of interest enables high spatial resolution acquisition of the flow field.
Introduction
Shear induced multimerisation of von-Willebrand-factor (vWF) is supposed to play an important role in coagulation inside extracorporeal membrane oxygenators. However, there is no proof that links observed vWF structures to computed or measured flow conditions.
Methods
The structures of multimeric vWF fibers, observed in clinically used membrane oxygenators is examined using immunofluorescence microscopy (IFM) using Carstairs’ staining method (positive ethics committee vote). The flow around the membrane fibres inside the oxygenator is investigated in terms of shear rate, wall shear velocity and streamlines by using CFD (RANS, Carreau-Yasuda viscosity, geometry remodelled after high-resolution µCT-scans). By interpreting the histological and numerical results in this common context, indications for shear induced coagulation mechanisms can be identified.
Results
The fibre structures of multimeric vWF build regular but not exactly symmetric formations around the contact face (CF) between the crosswise stacked oxygenator fibres (OF), see fig.1B, vWF marked red. Annular around the CF arranged, cells are likely to be found, see fig.1B, nuclei marked blue.
The computed streamlines around the OF show attached flow around the circular fibres. However, the irregular arrangement of real OF produce considerable cross flow between the interconnected neighbouring channels, in contrast to previous 2D-simulations. Thus, the CF are washed around closely by blood, also from neighbouring channels. The wall shear velocity streamlines form regular, slightly asymmetric shapes around the contact faces. The occurring maximum shear rates are in the range of 1,000 1/s.
Discussion
The shapes of vWF structures found in clinically used oxygenators match the computational results in terms of wall shear velocity and streamlines well. The accumulation of cells close to the CF can also be explained by fluid mechanics, as there are small shear gradients and slow velocities. However, occurring shear rates between OFs are too low to trigger multimerisation of vWF. That raises the question where in the circuit the actual activation of vWF is started and how, at least partly chained, vWF multimeres are attracted towards the OF surface. A next step will be the investigation of the actual shear rate triggered (or mediated) multimerisation of vWF. Towards this end, microfluidic experiments with shear triggered coagulation will be performed. Also of big interest is the computation of the flow situation in the oxygenator in proximity to chaining threads, which have been ignored in computations so far. However, first a realistic representation of the effective viscosity in computations is needed, which is not available yet.
Für Mutter und Kind konnte das Risiko der Geburt durch die Weiterentwicklung der Medizin drastisch reduziert werden. Doch wie ist es um das Wohl derer bestellt, die die Gebärende unterstützen? Eine Studie der Ostbayerischen Technischen Hochschule Regensburg hat sich mit den muskuloskelettalen Beschwerden von Geburtshelfer:innen auseinandergesetzt
Osteoporosis is a common disease of old age. However, in many cases, it can be very well prevented and counteracted with physical activity, especially high-impact exercises. Wearables have the potential to provide data that can help with continuous monitoring of patients during therapy phases or preventive exercise programs in everyday life. This study aimed to determine the accuracy and reliability of measured acceleration data at different body positions compared to accelerations at the pelvis during different jumping exercises. Accelerations at the hips have been investigated in previous studies with regard to osteoporosis prevention. Data were collected using an IMU-based motion capture system (Xsens) consisting of 17 sensors. Forty-nine subjects were included in this study. The analysis shows the correlation between impacts and the corresponding drop height, which are dependent on the respective exercise. Very high correlations (0.83–0.94) were found between accelerations at the pelvis and the other measured segments at the upper body. The foot sensors provided very weak correlations (0.20–0.27). Accelerations measured at the pelvis during jumping exercises can be tracked very well on the upper body and upper extremities, including locations where smart devices are typically worn, which gives possibilities for remote and continuous monitoring of programs.
Influence of CFD Strategy on WSS and OSI Determination for Intracranial Aneurysm Rupture Assessment
(2019)
Feasibility of detecting thrombotic deposits in membrane oxygenators using micro computed tomography
(2019)
Coagulative disorders, especially clotting during extracorporeal membrane oxygenation, are frequent complications. Direct visualization and analysis of deposits in membrane oxygenators using computed tomography (CT) may provide an insight into the underlying mechanisms causing thrombotic events. However, the already established multidetector CT1 (MDCT) method shows major limitations. Here, we demonstrate the feasibility of applying industrial micro-CT (μCT) to circumvent these restrictions. Three clinically used membrane oxygenators were investigated applying both MDCT and μCT.
The scans were analyzed in terms of clot volume and local clot distribution. As validation, the clot volume was also determined from the fluid volume, which could be filled into the respective used oxygenator compared to a new device. In addition, cross-sectional CT images were compared with crosscut oxygenators. Based on the μCT findings, a morphological measure (sphericity) for assessing clot structures in membrane oxygenators is introduced. Furthermore, by comparing MDCT and μCT results, an augmentation of the MDCT method is proposed, which allows for improved clot volume determination in a clinical setting.
Clot formation within membrane oxygenators (MOs) remains a critical problem during extracorporeal membrane oxygenation (ECMO). The composition of the clots—in particular, the presence of von Willebrand factor (vWF)—may be an indicator for prevalent nonphysiological flow conditions, foreign body reactions, or coagulation abnormalities in critically ill patients. Mats of interwoven gas exchange fibers from randomly collected MOs (PLS, Maquet, Rastatt, Germany) of 21 patients were stained with antibodies (anti‐vWF and anti‐P‐selectin) and counterstained with 4′,6‐diamidino‐2‐phenylindole. The extent of vWF‐loading was correlated with patient and technical data. While 12 MOs showed low vWF‐loadings, 9 MOs showed high vWF‐loading with highest accumulations close to crossing points of adjacent gas fibers. The presence and the extent of vWF‐fibers/“cobwebs,” leukocytes, platelet–leukocyte aggregates (PLAs), and P‐selectin‐positive platelet aggregates were independent of the extent of vWF‐loading. However, the highly loaded MOs were obtained from patients with a significantly elevated SOFA score, severe thrombocytopenia, and persistent liver dysfunction. The coagulation abnormalities of these critically ill patients may cause an accumulation of the highly thrombogenic and elongated high‐molecular‐weight vWF multimers in the plasma which will be trapped in the MOs during the ECMO therapy.
The special wing geometry of dragonflies consisting of veins and a membrane forming a corrugated profile leads to special aerodynamic characteristics. To capture the governing flow regimes of a dragonfly wing in detail, a realistic wing model has to be investigated. Therefore, this study aimed to analyze the aerodynamic characteristics of a 3D dragonfly wing reconstructed from a high-resolution micro-CT scan. Afterwards, a spatially high discretized mesh was generated using the mesh generator CENTAUR™ 14.5.0.2 (CentaurSoft, Austin, TX, US) to finally conduct Computational Fluid Dynamics (CFD) investigations in Fluent® 2020 R2 (ANSYS, Inc., Canonsburg, PA, US). Due to the small dimensions of the wing membrane, only the vein structure of a Camacinia Gigantea was captured at a micro-CT voxel size of 7 microns. The membrane was adapted and connected to the vein structure using a Boolean union operation. Occurring nconsistencies after combining the veins and the membrane were corrected using an adapted pymesh script [1]. As an initial study, only one quarter of the wing (outer wing section) was investigated to reduce the required computational effort. The resulting hybrid mesh consisting of 10 pseudo-structured prism layers along the wing surface and tetrahedra in the farfield area has 43 mio. nodes. The flow around the wing was considered to be incompressible and laminar using transient calculations. When the flow passes the vein structures, steady vortices occur in the corrugation valleys leading to recirculation zones. Therefore, the dragonfly wing resembles the profile of an airfoil. This leads to comparable lift coefficients of dragonfly wings and airfoil profiles at significantly reduced structural weight. The reconstructed geometry also included naturally occurring triangular prismlike serrated structures at the leading edge of the wing, which have comparable effects to micro vortex generators and might stabilize the recirculation zones. Further work aims to investigate the aerodynamic properties of a complete dragonfly wing during wing flapping.
Air leakage past High-Volume-Low-Pressure (HVLP) endotracheal tube (ETT) cuffs creates a potential infection risk for health care professionals during ventilation of patients suffering from contagious airborne diseases. However, unlike silent aspiration, a phenomenon where fluids enter the airways of intubated patients, the aspect of aerosol emergence through cuff folds -what we called accordingly “silent breathing” (SB)- has not been investigated in detail so far.
This study investigates air leakage past HVLP cuffs with varying cuff pressures under realistic artificial breathing scenarios experimentally and in addition numerically. The focus was laid on the parametric investigation of the occurrence and furthermore on different influencing factors of silent breathing. The morphology of the folds responsible for the leakage was captured using high-resolution 3D microcomputed tomography (μCT). For the numerical investigations (Com-putational Fluid Dynamics - CFD), the commercial CFD Software package FLUENT 2021 R2 (ANSYS, Inc., Canonsburg, PA, US), as well as the DLR in-house research code THETA has been used.
High Spatial Resolution Tomo-PIV of the Nasopharynx Focussing on the Physiological Breathing Cycle
(2022)
Investigations of complex patient-specific flow in the nasopharynx requires high resolution numerical calculations validated by reliable experiments. When building the validation base and the benchmark
of computational fluid dynamics, an experimental setup of the nasal airways was developed. The applied optical measurement technique of tomo-PIV supplies information on the governing flow field in three dimensions. This paper presents tomo-PIV measurements of the highly complex patient-specific geometry of the human trachea. A computertomographic scan of a person’s head builds the basis of the experimental silicone model of the nasal airways. An optimised approach for precise refractive index matching avoids optical distortions even in highly complex non-free-of-sight 3D geometries. A linear-motor-driven pump generates breathing scenarios, based on measured breathing cycles. Adjusting of the CCD cameras‘ double-frame-rate PIV-Δt enables the detailed analysis of flow structures during different cycle phases. Merging regions of interest enables high spatial resolution acquisition of the flow field.
Surgical smoke has been a little discussed topic in the context of the current pandemic. Surgical smoke is generated during the cauterization of tissue with heat-generating devices and consists of 95% water
vapor and 5% cellular debris in the form of particulate matter. In-vivo investigations are performed during tracheotomies where surgical smoke is produced during tissue electrocautery. Furthermore, in-vitro parametric studies to investigate the particle number and size distribution and the spatial distribution of surgical smoke with laser light sheet technique are conducted. The higher the power of the high-frequency-device the larger the particles in size and the higher the resulting particle counts. The images taken show the densest smoke at 40W with artificial saliva. The resulting characteristic size distribution, which may include viruses and bacterial components, confirms that the risk arising from surgical smoke should be considered. Furthermore, the experiments will provide the database for further numerical investigations.
Clot formation within membrane oxygenators (MOs) remains a critical problem during extracorporeal membrane oxygenation (ECMO). The composition of the clots-in particular, the presence of von Willebrand factor (vWF)-may be an indicator for prevalent nonphysiological flow conditions, foreign body reactions, or coagulation abnormalities in critically ill patients. Mats of interwoven gas exchange fibers from randomly collected MOs (PLS, Maquet, Rastatt, Germany) of 21 patients were stained with antibodies (anti-vWF and anti-P-selectin) and counterstained with 4 ',6-diamidino-2-phenylindole. The extent of vWF-loading was correlated with patient and technical data. While 12 MOs showed low vWF-loadings, 9 MOs showed high vWF-loading with highest accumulations close to crossing points of adjacent gas fibers. The presence and the extent of vWF-fibers/"cobwebs," leukocytes, platelet-leukocyte aggregates (PLAs), and P-selectin-positive platelet aggregates were independent of the extent of vWF-loading. However, the highly loaded MOs were obtained from patients with a significantly elevated SOFA score, severe thrombocytopenia, and persistent liver dysfunction. The coagulation abnormalities of these critically ill patients may cause an accumulation of the highly thrombogenic and elongated high-molecular-weight vWF multimers in the plasma which will be trapped in the MOs during the ECMO therapy.
Modelling blood flow an shear induced coagulation in membraene oxygenators (MO) is challenging. The relevant geometry of oxygenator fibers (OF) and chaining threads is complex and spans several length scales. In relevant scales and regimes blood shows several significant non-Newtonian effects. Existing models are only capable of accounting for some, but not all relevant effects. Additionally, coagulation processes are influencing fluid properties and geometry significantly. Due to the enormous size of the discretised geometries highly detailed viscosity and coagulation properties of blodd flow in MOs. First step is to find a gemoetry dependent viscosity representation on basis of parametric micro channel experiments with anti-coagulated blood. Next step is a statistic coagulation model, based on micro channel experiments with human (re-calcified citrated) whole blood an evaluation of clinically used osygenators. Since shear rate dependent (i.e. viscosity dependet) coagulation in return influences the viscosity, a combined model with suitable implementation in a RANS framework is necessary. Towards this end, micro channel experiments with new and used single OFs triggering coagulation are performed. Structures of multimeric von Willebrand fibers (vWF), as indicator for shear induced coagulation, are compared to computed and measured flow conditions, using immunofluorescence microscopy, RANS-computations and µPIV, respectively. Preliminary examinations in clinically used MOs show good agreement between occurring structures of vWF, cell depositions and computed flow patterns (geometry form µCT-Scans). However, computed shear rates might be to low to actually trigger activation of vWF. The complex geometry of MOs results in huge meshes, which makes RANS with statistical modelling of viscosity and coagulation a reasonable approach. Towards this end, experimental data on micro channel level with evaluation on real application level is crucial. Especially regarding clotting processes, micro fluidic experiments are powerful research tool.
BACKGROUND:
Shear-induced conformational changes of von Willebrand factor (vWF) may be responsible for coagulation disorder and clot formation inside membrane oxygenators (MOs) during extracorporeal membrane oxygenation (ECMO) therapy.
OBJECTIVE:
The aim was to identify vWF structures inside clinically used MOs and employ computational fluid dynamics to verify the corresponding flow conditions.
METHODS:
Samples from gas exchange membranes (GEM) from MOs were analysed for accumulations of vWF and P-selectin-positive platelets using immunofluorescence techniques. Streamlines and shear rates of the flow around GEMs were computed using a laminar steady Reynolds-Averaged-Navier-Stokes approach.
RESULTS:
Most samples were colonized with equally distributed leukocytes, integrated in thin cobweb-like vWF-structures. Only 25 % of the samples showed extended accumulations of vWF. Computed streamlines showed considerable cross flow between interconnected neighbouring channels. Stagnation points were non-symmetric and contact faces were washed around closely. The occurring maximum shear rates ranged from 2,500 to 3,000 1/s.
CONCLUSIONS:
If pronounced vWF structures are present, shape and extent match the flow computations well. Computed shear rates bear a critical degree of uncertainty due to the improper viscosity model. If flow conditions inside the MO were sufficient to affect vWF, a more consistent distribution of vWF across the samples should be present.
Exoskeletons were invented over 100 years ago but have only become popular in the last two decades, especially in the working industry as they can decrease work-related loads significantly. The most often used exoskeletons are for the lower back and shoulder since these are commonly affected body regions. All devices have in common that their purpose is to reduce internal loads of vulnerable body regions. Nevertheless, there is still little understanding on how biomechanical loading in the human body changes when exoskeletons are used. Therefore, further analyses are needed. A promising candidate for these are musculoskeletal models, which are based on an inverse dynamics approach and can calculate external parameters such as ground reaction forces or other interaction forces as well as internal parameters such as joint reaction forces or muscle activities. The various examples in the literature show that these models are increasingly used for assessing the biomechanical effects of exoskeletons on the human body. Furthermore, musculoskeletal models can calculate biomechanical loadings of humans with and without exoskeletons for all kinds of applications and allow an evaluation of their purpose.
Practical Relevance: This article highlights the possibilities of musculoskeletal models for assessing the design and efficiency of occupational exoskeletons. Several practical use cases are described along with distinct descriptions of common implications of musculoskeletal and exoskeleton modeling.
Innovationsmanagement
(2011)
Das Management in der Medizinprodukteindustrie steht vor vielfältigen Herausforderungen. So sinken einerseits die Produktpreise, anderseits wird auch für die kommenden Jahre in vielen Segmenten ein Mengenwachstum erwartet. Dies stellt die internen Prozesse, vom Customer Service bis hin zur Forschung & Entwicklung, auf den Prüfstand. Die Entscheidungsträger auf Kundenseite verändern sich, weg vom Produktanwender hin zu professionellen Einkaufsgemeinschaften mit immer größerer Verhandlungsmacht. Der hohe Internationalisierungsgrad der Unternehmen führt zu einer steigenden Komplexität bei der Implementierung von Marketing-, Vertriebs- und Produktentwicklungsstrategien auf Länderebene. Darüber hinaus werden zunehmend neue Geschäftsmodelle mit hohem Dienstleistungsanteil entwickelt, die mit der traditionellen Lieferantenrolle wenig zu tun haben und von Managern eine neue Fähigkeiten für die Umsetzung erfordern. Die Autoren des Sammelbands greifen die genannten Herausforderungen auf und bieten mit ihren Beiträgen Lösungsansätze, die sowohl für Manager im Medizinprodukteunternehmen als auch für Wissenschaftler und Studierende relevant sind.
The Impact of the ObamaCare Excise Tax on Innovation and Entrepreneurship – Early Empirical Findings
(2015)
This study addresses aspects of governmental influence on innovation by analyzing the impact of the ObamaCare excise tax on the medical device industry. We initially give an overview of common approaches to measuring innovativeness and entrepreneurship, empirically assess whether existing metrics are suitable for investigating the innovation performance of the U.S. medical device industry, and define a new measure (firm innovation activity) for entrepreneurship. Then we perform a quantitative analysis to explore the impact of the tax. We analyze more than 60,000 product clearances from 1996 to 2013, using the FDA database. We find a significant relationship between product counts and revenues for one segment. Contrary to the present criticism of the excise tax, we find hardly any noteworthy response in either firm innovation activity or number of products launched in the year after the tax was introduced. The 2013 reduction of new product submissions is well within the limits of typical annual fluctuations observed in previous years. This provides a first indication that the excise tax act did not have a strong impact on innovative activities through the present.
Introduction:
Neointimal hyperplasia after percutaneous coronary intervention remains a major determinant of in-stent restenosis (ISR). The extent of mechanical vessel injury correlates with ISR. A new ex vivo porcine stent model was introduced and evaluated comparing different stent designs.
Methods:
Coronary arteries were prepared from pig hearts from the slaughterhouse and used for ex vivo implantations of coronary stents. One basic stent design in two configurations (dogbone, DB; non-dogbone, NDB) was used. Vascular injury was determined according to a modified injury score (IS).
Results:
Standardized experimental conditions ensured comparable vessel dimensions and overstretch data. DB stents caused more severe IS compared to NDB stents. The mean IS and the IS at the distal end of all stents were significantly reduced for NDB stents (ISMean, DB, 1.16 ±0.12; NDB, 1.02 ±0.12; p=0.018; ISDist, DB, 1.39 ±0.28; NDB, 1.13 ±0.24; p=0.03).
Discussion/Conclusion:
The introduced ex-vivo model allowed the evaluation of different stent designs exclude unfavorable stent designs.
The good availability and the large content of adult stem cells in adipose tissue has made it one of the most interesting tissues in regenerative medicine. Although lipofilling is one of the most frequent procedures in plastic surgery, the method still struggles with high absorption rates and volume losses of up to 70%. Therefore, many efforts have been made to optimize liposuction and to process the harvested tissue in order to increase fat graft retention. Because of their immunomodulatory properties, their cytokine secretory activity, and their differentiation potential, enrichment with adipose tissue-derived stem cells was identified as a promising tool to promote transplant survival. Here, we review the important parameters for lipofilling optimization. Finally, we present a new method for the enrichment of lipoaspirate with adipose tissue-derived stem cells and discuss the parameters that contribute to fat graft survival.
Elbow stability is derived from a combination of muscular, ligamentous, and bony structures. After an elbow trauma the stability of the joint is an important decision criterion for the subsequent treatment. The decision regarding non-operative/operative care depends mostly on subjective assessments of medical experts. Therefore, the aim of this study is to use musculoskeletal simulations as an objective assessment tool to investigate the extent to which failure of different stabilizers affects the elbow stability and how these observations correspond to the assessment from clinical practice. A musculoskeletal elbow simulation model was developed for this aim. To investigate the stability of the elbow, varus/valgus moments were applied under 0°, 45°and 90° flexion while the respective cubital angle was analyzed. This was performed for nine different injury scenarios, which were also evaluated for stability by clinical experts. With the results, it can be determined by which injury pattern and under which flexion angle the elbow stability is impaired regarding varus/valgus moments. The scenario with a complete failure of the medial and lateral ligaments and a fracture of the radial head was identified as having the greatest instability. The study presented a numerical determination of elbow stability against varus/valgus moments regarding clinical injury patterns, as well as a comparison of the numerical outcome with experience gained in clinical practice. The numerical predictions agree well with the assessments of the clinical specialists. Thus, the results from musculoskeletal simulation can make an important contribution to a more objective assessment of the elbow stability.
Autologous lipotransfer is a promising method for tissue regeneration, because white adipose tissue contains a heterogeneous cell population, including mesenchymal stem cells, endothelial cells, immune cells, and adipocytes. In order to improve the outcome, adipose tissue can be processed before application. In this study, we investigated changes caused by mechanical processing.
Lipoaspirates were processed using sedimentation, first-time centrifugation, shear-force homogenization, and second-time centrifugation. The average adipocyte size, stromal vascular cell count, and adipocyte depot size were examined histologically at every processing step. In addition, the adipose derived stem cells (ADSCs) were isolated and differentiated osteogenically and adipogenically. While homogenization causes a disruption of adipocyte depots, the shape of the remaining adipocytes is not changed. On average, these adipocytes are smaller than the depot adipocytes, they are surrounded by the ECM, and therefore mechanically more stable. The volume loss of adipocyte depots leads to a significant enrichment of stromal vascular cells such as ADSCs. However, the mechanical processing does not change the potential of the ADSCs to differentiate adipogenically or steogenically. It thus appears that mechanically processed lipoaspirates are promising for the reparation of even mechanically stressed tissue as that found in nasolabial folds. The changes resulting from the processing correspond more to a filtration of mechanically less stable components than to a manipulation of the tissue.
Medical Device Regulation
(2019)
Die Aufmerksamkeit für Unternehmensgründungen hat in den letzten Jahren extrem zugenommen. Grundsätzlich muss ein Start-up in einem kompetitiven Umfeld erfolgreich sein, um bestehen zu können. Der Weg dorthin wird maßgeblich beeinflusst durch Planung und finanzielle Ressourcen, die die Gründer bereitstellen müssen. In der Medizinprodukteindustrie kommen zusätzlich große Hürden hinzu, die u. a. einen kurzen Produktlebenszyklus, lange Projektlaufzeiten, aufwendige klinische Studien und aktuell neue gesetzliche Verordnungen betreffen. Dieser Beitrag konzentriert sich zunächst auf mögliche Fördermittel und Beratung von Start-up-Projekten aus dem Hochschulbereich. Aus einer Analyse derzeit existierender Gründerwettbewerbe im Hinblick auf das Gesundheitswesen werden dem Leser entsprechende Adressen zum Einwerben von Fördermitteln geliefert. Darüber hinaus wird ein Pilot-Prozess vorgestellt, wie eine Ausgründungsberatung an der Hochschule Ulm im Studiengang Medizintechnik derzeit verläuft. Dies kann möglicherweise ein Anknüpfungspunkt für eine zukünftige Institutionalisierung von Spin-off-Vorhaben aus dem Hochschulbereich sein.
Convolutional Neural Networks for Approximation of Internal Non-Newtonian Multiphase Flow Fields
(2021)
Neural networks (NNs) as an alternative method for universal approximation of differential equations have proven to be computationally efficient and still sufficiently accurate compared to established methods such as the finite volume method (FVM). Additionally, analysing weights and biases can give insights into the underlying physical laws. FVM and NNs are both based upon spacial discretisation. Since a Cartesian and equidistant grid is a raster graphics, image-to-image regression techniques can be used to predict phase velocity fields as well as particle and pressure distributions from simple mass flow boundary conditions. The impact of convolution layer depth and number of channels of a ConvolutionDeconvolution Regression Network (CDRN), on prediction performance of internal non-Newtownian multiphase flows is investigated. Parametric training data with 2055 sets is computed using FVM. To capture significant non-Newtownian effects of a particle-laden fluid (e.g. blood) flowing through small and non-straight channels, an Euler-Euler multiphase approach is used. The FVM results are normalized and mapped onto an equidistant grid as supervised learning target. The investigated NNs consist of n= {3, 5, 7} corresponding encoding/decoding blocks and different skip connections. Regardless of the convolution depth (i.e. number of blocks), the deepest spacial down-sampling via strided convolution is adjusted to result in a 1 × 1 × f · 2nfeature map, with f = {8, 16, 32}. The prediction performance expressed is as channel-averaged normalized root mean squared error (NRMSE). With a NRMSE of < 2 · 10-3, the best preforming NN has f = 32 initial feature maps, a kernel size of k = 4, n = 5 blocks and dense skip connections. Average inference time from this NN takes < 7 · 10-3s. Worst accuracy at NRMSE of approx 9 · 10-3is achieved without any skips, at k = 2, f = 16 and n = 3, but deployment takes only < 2 · 10-3s Given an adequate training, the prediction accuracy improves with convolution depth, where more features have higher impact on deeper NNs. Due to skip connections and batch normalisation, training is similarly efficient, regardless of the depth. This is further improved by blocks with dense connections, but at the price of a drastically larger model. Depending on geometrical complexity, spacial resolution is critical, as it increases the number of learnables and memory requirements massively.
Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence, histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene expression patterns, and cell fate decisions, represent promising new drugs for the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side effects. We present the synthesis and biological evaluation of Marbostats, novel HDAC6i that contain the hydroxamic acid moiety linked to tetrahydro-β-carboline derivatives. Our lead compound Marbostat-100 is a more potent and more selective HDAC6i than previously established well-characterized compounds in vitro as well as in cells. Moreover, Marbostat-100 is well tolerated by mice and effective against collagen type II induced arthritis. Thus, Marbostat-100 represents a most selective known HDAC6i and the possibility for clinical evaluation of a HDAC isoform-specific drug.
Over the past decade, veno-venous extracorporeal membrane oxygenation (vvECMO) has been increasingly utilized in respiratory failure in patients. This study presents our institution´s experience focusing on the life span of ECMO systems reflecting the performance of a particular system. A retrospective review of our ECMO database identified 461 adult patients undergoing vvECMO (2010-2017). Patients that required more than one system and survived the first exchange >24 hours (n = 139) were included. Life span until the first exchange and exchange criteria were analyzed for all systems (PLS, Cardiohelp HLS-set, both Maquet Cardiopulmonary, Rastatt, Germany; Deltastream/Hilite7000LT, iLA-activve, Xenios/NovaLung, Heilbronn, Germany; ECC.O5, LivaNova, Mirandola, Italy). At our ECMO center, the frequency of a system exchange was 30%. The median (IQR) life span was 9 (6-12) days. There was no difference regarding the different systems (p = 0.145 and p = 0.108, respectively). However, the Deltastream systems were exchanged more frequently due to elective technical complications (e. g. worsened gas transfer, development of coagulation disorder, increased bleedings complications) compared to the other exchanged systems (p = 0.013). In summary, the used ECMO systems are safe and effective for acute respiratory failure. There is no evidence for the usage of a specific system. Only the increased predictability of an imminent exchange preferred the usage of a Deltastream system. However, the decision to use a particular system should not depend solely on the possible criteria for an exchange.
Blood flow in channels of varying diameters <500μm exhibits strong non-linear effects. Multiphase finite volume approaches are feasible, but still computationally costly. Here, the feasibility of applying convolutional neural networks for blood flow prediction in artificial lungs is investigated. Training targets are precomputed using an Eulerian two-phase approach. To match with experimental data, the interphase drag and lift, as well as intraphase shear-thinning are adapted. A recursively branching regression network and convolution/deconvolution networks with plain skip connections and densely connected skips are investigated. A priori knowledge is incorporated in the loss functional to prevent the network from learning non-physical solutions. Inference from neural networks is approximately six orders of magnitude faster than the classical finite volume approach. Even if resulting in comparably coarse flow fields, the neural network predictions can be used as close to convergence initial solutions greatly accelerating classical flow computations.
Resting motor threshold and magnetic field output of the figure-of-8 and the double-cone coil
(2020)
The use of the double-cone (DC) coil in transcranial magnetic stimulation (TMS) is promoted with the notion that the DC coil enables stimulation of deeper brain areas in contrast to conventional figure-of-8 (Fo8) coils. However, systematic comparisons of these two coil types with respect to the spatial distribution of the magnetic field output and also to the induced activity in superficial and deeper brain areas are limited. Resting motor thresholds of the left and right first dorsal interosseous (FDI) and tibialis anterior (TA) were determined with the DC and the Fo8 coil in 17 healthy subjects. Coils were orientated over the corresponding motor area in an angle of 45 degrees for the hand area with the handle pointing in posterior direction and in medio-lateral direction for the leg area. Physical measurements were done with an automatic gantry table using a Gaussmeter. Resting motor threshold was higher for the leg area in contrast to the hand area and for the Fo8 in contrast to the DC coil. Muscle by coil interaction was also significant providing higher differences between leg and hand area for the Fo8 (about 27%) in contrast to the DC coil (about 15%). Magnetic field strength was higher for the DC coil in contrast to the Fo8 coil. The DC coil produces a higher magnetic field with higher depth of penetration than the figure of eight coil.
BACKGROUND:
Due to their corrugated profile, dragonfly wings have special aerodynamic characteristics during flying and gliding. OBJECTIVE: The aim of this study was to create a realistic 3D model of a dragonfly wing captured with a high-resolution micro-CT. To represent geometry changes in span and chord length and their aerodynamic effects, numerical investigations are carried out at different wing positions. METHODS:
The forewing of a Camacinia gigantea was captured using a micro-CT. After the wing was adapted an error-free 3D model resulted. The wing was cut every 5 mm and 2D numerical analyses were conducted in Fluent® 2020 R2 (ANSYS, Inc., Canonsburg, PA, USA). RESULTS: The highest lift coefficient, as well as the highest lift-to-drag ratio, resulted at 0 mm and an angle of attack (AOA) of 5∘. At AOAs of 10∘ or 15∘, the flow around the wing stalled and a Kármán vortex street behind the wing becomes
CONCLUSIONS:
The velocity is higher on the upper side of the wing compared to the lower side. The pressure acts vice versa. Due to the recirculation zones that are formed in valleys of the corrugation pattern the wing resembles the form of an airfoil.
Ergonomic workplaces lead to fewer work-related musculoskeletal disorders and thus fewer sick days. There are various guidelines to help avoid harmful situations. However, these recommendations are often rather crude and often neglect the complex interaction of biomechanical loading and psychological stress. This study investigates whether machine learning algorithms can be used to predict mechanical and stress-related muscle activity for a standardized motion. For this purpose, experimental data were collected for trunk movement with and without additional psychological stress. Two different algorithms (XGBoost and TensorFlow) were used to model the experimental data. XGBoost in particular predicted the results very well. By combining it with musculoskeletal models, the method shown here can be used for workplace analysis but also for the development of real-time feedback systems in real workplace environments.
Biomechanical analysis of the right elevated glenohumeral joint in violinists during legato-playing
(2022)
BACKGROUND:
Many statistics reveal that violin players suffer most often from musculoskeletal disorders compared to musicians of other instrument groups. A common phenomenon, especially observed in violin beginners, is the tendency to elevate the right shoulder during playing the violin. This can probably lead to serious disorders in long-term practice with repetitive movements.
OBJECTIVE:
For this reason, this study investigated the relationship between the right shoulder elevation and the force in the right glenohumeral joint during violin playing. It was hypothesized that the forces in the right glenohumeral joint are higher during playing with the right shoulder raised compared to playing in normal posture.
METHODS:
Motion capture data from four experienced violinists was recorded and processed by means of musculoskeletal simulation to get the force and elevation angle while playing with raised shoulder and in normal position.
RESULTS:
The results indicate that the absolute values of the resulting force, as well as the forces in the mediolateral, inferosuperior, and anteroposterior directions, are higher in playing the violin with the shoulder raised than in a normal posture.
CONCLUSIONS:
Elevating the right shoulder while playing the violin may pose a potential problem.
Objective
The risk of in-stent restenosis can be considerably reduced by stents eluting cytostatic compounds. We created a novel drug-eluting stent system that includes several new features in the rapidly evolving field of stent-based drug delivery.
Methods and Results
The aim of the present study was the preclinical evaluation of a stent-coating system permitting individual, on-site coating of stents with a unique microporous surface allowing for individualizable, dose-adjustable, and multiple coatings with identical or various compounds, designated ISAR (individualizable drug-eluting stent system to abrogate restenosis). Stents were coated with 0.75% rapamycin solution, and high-performance liquid chromatography (HPLC)-based determination of drug release profile indicated drug release for >21 days. Rapamycin-eluting microporous (REMP) stents implanted in porcine coronary arteries were safe. To determine the efficacy of REMP stents, this novel drug-eluting stent platform was compared with the standard sirolimus-eluting stent. At 30 days, in-stent neointima formation in porcine coronary arteries was similar in both groups, yielding a significant decrease of neointimal area and injury-dependent neointimal thickness compared with bare-metal stents.
Conclusion
The ISAR drug-eluting stent platform as a novel concept for stent coating allows for a safe, effective, on-site stent coating process, thus justifying further clinical evaluation to decrease in-stent restenosis in humans.
In-stent neointima formation can be successfully attenuated by drug-eluting stents. We introduce a novel conceptual approach for stent-coating that allows for dose-adjustable, on-site stent coating process if desired with multiple compounds. Microporous stents coated with rapamycin proved safe and effective for the limitation of neointima formation in a porcine coronary stent model.
Aims
Drug-eluting stents (DES) represent a major advance in interventional cardiology. Along with the success shown, current DES also present limitations related to the presence of polymer-coating, fixed drug, and dose used. With the ISAR (Individualized Drug-Eluting Stent System to Abrogate Restenosis) project, a DES system has been developed that permits individualized choice of the drug and dose to use for the given patient. The objective of this prospective dose finding study was to assess the feasibility, safety, and efficacy of a polymer-free on-site stent coating with increasing rapamycin doses.
Methods and results
In this dose finding study, 602 patients were sequentially enrolled in four groups: microporous bare metal stent (BMS), DES stents coated with a 0.5, 1.0, and 2.0% rapamycin solution. The angiographic in-segment restenosis rate at follow-up angiography was the primary study endpoint. In-segment restenosis was significantly reduced from 25.9% with BMS to 18.9, 17.2, and 14.7% with 0.5, 1.0, and 2.0% rapamycin-eluting stents, respectively (P=0.024). Similarly, the need for target lesion revascularization at 1 year follow-up was reduced from 21.5% with BMS to 16.4, 12.6, and 8.8% with 0.5, 1.0, and 2.0% rapamycin-eluting stents, respectively (P=0.006).
Conclusion
The placement of polymer-free stents coated on-site with rapamycin is feasible and safe. Furthermore, a dose-dependent efficacy in restenosis prevention is achievable with this new DES concept.
Vascular damage develops with diverging severity during and after percutaneous coronary intervention with stent placement and is the prevailing stimulus for in-stent restenosis. Previous work has failed to link mechanical data obtained in a realistic in vivo or in vitro environment with data collected during imaging processes. We investigated whether specimens of porcine right coronary arteries soften when indented with a stent strut shaped structure, and if the softening results from damage mechanisms inside the fibrillar collagen structure. To simulate the multiaxial loading scenario of a stented coronary artery, we developed the testing device ‘LAESIO’ that can measure differences in the stress-stretch behavior of the arterial wall before and after the indentation of a strut-like stamp. The testing protocol was optimized according to preliminary experiments, more specifically equilibrium and relaxation tests. After chemical fixation of the specimens and subsequent tissue clearing, we performed three-dimensional surface and second-harmonic generation scans on the deformed specimens. We analyzed and correlated the mechanical response with structural parameters of high-affected tissue located next to the stamp indentation and low-affected tissue beyond the injured area. The results reveal that damage mechanisms, like tissue compression as well as softening, fiber dispersion, and the lesion extent, are direction-dependent, and the severity of them is linked to the strut orientation, indentation pressure, and position. The findings highlight the need for further investigations by applying the proposed methods to human coronary arteries. Additional data and insights might help to incorporate the observed damage mechanisms into material models for finite element analyses to perform more accurate simulations of stent-implantations.
Experimental and mathematical characterization of coronary polyamide-12 balloon catheter membranes
(2020)
The experimental quantification and modeling of the multiaxial mechanical response of polymer membranes of coronary balloon catheters have not yet been carried out. Due to the lack of insights, it is not shown whether isotropic material models can describe the material response of balloon catheter membranes expanded with nominal or higher, supra-nominal pressures. Therefore, for the first time, specimens of commercial polyamide-12 balloon catheters membranes were investigated during uniaxial and biaxial loading scenarios. Furthermore, the influence of kinematic effects on the material response was observed by comparing results from quasi-static and dynamic biaxial extension tests. Novel clamping techniques are described, which allow to test even tiny specimens taken from the balloon membranes. The results of this study reveal the semi-compliant, nonlinear, and viscoelastic character of polyamide-12 balloon catheter membranes. Above nominal pressure, the membranes show a pronounced anisotropic mechanical behavior with a stiffer response in the circumferential direction. The anisotropic feature intensifies with an increasing strain-rate. A modified polynomial model was applied to represent the realistic mechanical response of the balloon catheter membranes during dynamic biaxial extension tests. This study also includes a compact set of constitutive model parameters for the use of the proposed model in future finite element analyses to perform more accurate simulations of expanding balloon catheters.
Background:
Lipofilling is one of the most often performed surgical procedures in plastic and reconstructive surgery. Lipoaspirates provide a ready source of stem cells and secreted factors that contribute to neoangiogenesis and fat graft survival. However, the regulations about the enrichment of these beneficial cells and factors are ambiguous. In this study, the authors tested whether a combination of centrifugation and homogenization allowed the enrichment of viable stem cells in lipoaspirates through the selective removal of tumescent solution, blood, and released lipids without significantly affecting the cell secretome.
Methods:
Human lipoaspirate was harvested from six different patients using water jet–assisted liposuction. Lipoaspirate was homogenized by first centrifugation (3584 rpm for 2 minutes), shear strain (10 times intersyringe processing), and second centrifugation (3584 rpm for 2 minutes). Stem cell enrichment was shown by cell counting after stem cell isolation. Lipoaspirate from different processing steps (unprocessed, after first centrifugation, after homogenization, after second centrifugation) was incubated in serum-free cell culture medium for mass spectrometric analysis of secreted proteins.
Results:
Lipoaspirate homogenization leads to a significant 2.6 ± 1.75-fold enrichment attributable to volume reduction without reducing the viability of the stem cells. Protein composition of the secretome did not change significantly after tissue homogenization. Considering the enrichment effects, there were no significant differences in the protein concentration of the 83 proteins found in all processing steps.
Conclusions:
Stem cells can be enriched mechanically without significantly affecting the composition of secreted proteins. Shear-assisted enrichment of lipoaspirate constitutes no substantial manipulation of the cells’ secretome.
Results of WICOVIR Gargle Pool PCR Testing in German Schools Based on the First 100,000 Tests
(2021)
Background:
Opening schools and keeping children safe from SARS-CoV-2 infections at the same time is urgently needed to protect children from direct and indirect consequences of the COVID-19 pandemic. To achieve this goal, a safe, efficient, and cost-effective SARS-CoV-2 testing system for schools in addition to standard hygiene measures is necessary.
Methods:
We implemented the screening WICOVIR concept for schools in the southeast of Germany, which is based on gargling at home, pooling of samples in schools, and assessment of SARS-CoV-2 by pool rRT-PCR, performed decentralized in numerous participating laboratories. Depooling was performed if pools were positive, and results were transmitted with software specifically developed for the project within a day. Here, we report the results after the first 13 weeks in the project.
Findings:
We developed and implemented the proof-of-concept test system within a pilot phase of 7 weeks based on almost 17,000 participants. After 6 weeks in the main phase of the project, we performed >100,000 tests in total, analyzed in 7,896 pools, identifying 19 cases in >100 participating schools. On average, positive children showed an individual CT value of 31 when identified in the pools. Up to 30 samples were pooled (mean 13) in general, based on school classes and attached school staff. All three participating laboratories detected positive samples reliably with their previously established rRT-PCR standard protocols. When self-administered antigen tests were performed concomitantly in positive cases, only one of these eight tests was positive, and when antigen tests performed after positive pool rRT-PCR results were already known were included, 3 out of 11 truly positive tests were also identified by antigen testing. After 3 weeks of repetitive WICOVIR testing twice weekly, the detection rate of positive children in that cohort decreased significantly from 0.042 to 0.012 (p = 0.008).
Interpretation:
Repeated gargle pool rRT-PCR testing can be implemented quickly in schools. It is an effective, valid, and well-received test system for schools, superior to antigen tests in sensitivity, acceptance, and costs.
Advances in additive manufacturing enable the production of tailored lattice structures and thus, in principle, coronary stents. This study investigates the effects of process-related irregularities, heat and surface treatment on the morphology, mechanical response, and expansion behavior of 316L stainless steel stents produced by laser powder bed fusion and provides a methodological approach for their numerical evaluation. A combined experimental and computational framework is used, based on both actual and computationally reconstructed laser powder bed fused stents. Process-related morphological deviations between the as-designed and actual laser powder bed fused stents were observed, resulting in a diameter increase by a factor of 2-2.6 for the stents without surface treatment and 1.3-2 for the electropolished stent compared to the as-designed stent. Thus, due to the increased geometrically induced stiffness, the laser powder bed fused stents in the as-built (7.11 ± 0.63 N) or the heat treated condition (5.87 ± 0.49 N) showed increased radial forces when compressed between two plates. After electropolishing, the heat treated stents exhibited radial forces (2.38 ± 0.23 N) comparable to conventional metallic stents. The laser powder bed fused stents were further affected by the size effect, resulting in a reduced yield strength by 41% in the as-built and by 59% in the heat treated condition compared to the bulk material obtained from tensile tests. The presented numerical approach was successful in predicting the macroscopic mechanical response of the stents under compression. During deformation, increased stiffness and local stress concentration were observed within the laser powder bed fused stents. Subsequent numerical expansion analysis of the derived stent models within a previously verified numerical model of stent expansion showed that electropolished and heat treated laser powder bed fused stents can exhibit comparable expansion behavior to conventional stents. The findings from this work motivate future experimental/numerical studies to quantify threshold values of critical geometric irregularities, which could be used to establish design guidelines for laser powder bed fused stents/lattice structures.
Biomechanical Analysis of the Right Elevated Glenohumeral Joint in Violinists during Legato-Playing
(2021)
BACKGROUND:
Many statistics reveal that violin players suffer most often from musculoskeletal disorders compared to musicians of other instrument groups. A common phenomenon, especially observed in violin beginners, is the tendency to elevate the right shoulder during playing the violin. This can probably lead to serious disorders in long-term practice with repetitive movements.
OBJECTIVE:
For this reason, this study investigated the relationship between the right shoulder elevation and the force in the right glenohumeral joint during violin playing. It was hypothesized that the forces in the right glenohumeral joint are higher during playing with the right shoulder raised compared to playing in normal posture.
METHODS:
Motion capture data from four experienced violinists was recorded and processed by means of musculoskeletal simulation to get the force and elevation angle while playing with raised shoulder and in normal position.
RESULTS:
The results indicate that the absolute values of the resulting force, as well as the forces in the mediolateral, inferosuperior, and anteroposterior directions, are higher in playing the violin with the shoulder raised than in a normal posture.
CONCLUSIONS: Elevating the right shoulder while playing the violin may pose a potential problem.
Regarding the prevention of injuries and rehabilitation of the human hand, musculoskeletal simulations using an inverse dynamics approach allow for insights of the muscle recruitment and thus acting forces on the hand. Currently, several hand models from various research groups are in use, which are mainly validated by the comparison of numerical and anatomical moment arms. In contrast to this validation and model-building technique by cadaver studies, the aim of this study is to further validate a recently published hand model [1] by analyzing numerically calculated muscle activities in comparison to experimentally measured electromyographical signals of the muscles. Therefore, the electromyographical signals of 10 hand muscles of five test subjects performing seven different hand movements were measured. The kinematics of these tasks were used as input for the hand model, and the numerical muscle activities were computed. To analyze the relationship between simulated and measured activities, the time difference of the muscle on- and off-set points was calculated, which resulted in a mean on- and off-set time difference of 0.58 s between the experimental data and the model. The largest differences were detected for movements that mainly addressed the wrist. One major issue comparing simulated and measured muscle activities of the hand is cross-talk. Nevertheless, the results show that the hand model fits the experiment quite accurately despite some limitations and is a further step toward patient-specific modeling of the upper extremity.
Musculoskeletal lower back load of accoucheurs during childbirth – A pilot and feasibility study
(2021)
Introduction: Back problems represent one of the leading causes of accouchers' work-related musculoskeletal morbidities. The correct execution of birth-related maneuvers including manual perineal protection is crucial not only for the mother and child but also for obstetricians and midwives to reduce any strain on their musculoskeletal system. Therefore, the overall aim of this study was to test the feasibility of determining the effect of different accouchers' postures (standing and kneeling) on their musculoskeletal system.
Methods: The biomechanical analysis is based on musculoskeletal simulations that included motion recordings of real deliveries as well as deliveries conducted on a birthing simulator. These simulations were then used to determine individual joints' loads.
Results: In the kneeling posture, both a low intra-operator variability and a lower average maximum load of the lower back was observed. For the standing position the spine load was reduced by pivoting the elbow on the accouchers' thigh, which in turn was associated with a significantly greater load on the shoulder joint.
Conclusion: The study demonstrated the feasibility of our technique to assess joints loads. It also provided initial data indicating that a posture that reduces spinal flexion and tilt, achieved in this study by the kneeling, can significantly reduce the strain on the practitioner's musculoskeletal system.
Football players have a high risk of leg muscle injuries, especially when exposed to mental stress. Injuries to muscles of the thigh are common in amateur and professional football, representing almost a third of all injuries. These injuries occur primarily in non-contact situations and from overuse. They can lead to a range of costs, including financial costs associated with treatment as well as those associated with long-term recovery, and absence from training and/or competition. Further, there is a high risk of injury recurrence and subsequent injury.
With the progress in modern medicine, it was possible to significantly reduce the risks of birth for mother and child. One aspect that has received less attention so far is the risk of injury to the accoucheurs (obstetricians and midwives) during the birth process. Indeed, studies indicate that 92% of midwives suffer from musculoskeletal disorders, with the lower back being the main cause of complaints (72%). The aim of this study was to investigate two commonly used postural techniques used by accoucheurs during childbirth and to analyze the resulting load on the lower back using the AnyBodyTM musculoskeletal simulation software.
Evaluation of muscle recruitment and muscle models in musculoskeletal simulation of dynamic motion
(2021)
Musculoskeletal simulation plays an increasingly important role in sports biomechanics. In the last years, the field of application widened from orthopaedics and ergonomics to sports [1]. A muscle recruitment algorithm with a quadratic objective function is usually used to calculate muscle activity in dynamic movements. The agreement of calculated and measured thigh muscle activity has already been investigated [2]. They found a strong agreement for sprinting and running, while the correlation decreased for side-cutting manoeuvres. Nevertheless, the influence of different muscle recruitment criteria on muscle activity in dynamic musculoskeletal simulations is currently unknown. Hence, this study aimed to analyse the effect of different muscle recruitment criteria and muscle models on the correlation of numerical and measured muscle activity in highly dynamic movements.