Use of portable air purifiers to reduce aerosols in hospital settings and cut down the clinical backlog.

SARS-CoV-2 has severely affected capacity in the National Health Service (NHS), and waiting lists are markedly increasing due to downtime of up to 50 min between patient consultations/procedures, to reduce the risk of infection. Ventilation accelerates this air cleaning, but retroactively installing built-in mechanical ventilation is often cost-prohibitive. We investigated the effect of using portable air cleaners (PAC), a low-energy and low-cost alternative, to reduce the concentration of aerosols in typical patient consultation/procedure environments. The experimental setup consisted of an aerosol generator, which mimicked the subject affected by SARS-CoV-19, and an aerosol detector, representing a subject who could potentially contract SARS-CoV-19. Experiments of aerosol dispersion and clearing were undertaken in situ in a variety of rooms with two different types of PAC in various combinations and positions. Correct use of PAC can reduce the clearance half-life of aerosols by 82% compared to the same indoor-environment without any ventilation, and at a broadly equivalent rate to built-in mechanical ventilation. In addition, the highest level of aerosol concentration measured when using PAC remains at least 46% lower than that when no mitigation is used, even if the PAC's operation is impeded due to placement under a table. The use of PAC leads to significant reductions in the level of aerosol concentration, associated with transmission of droplet-based airborne diseases. This could enable NHS departments to reduce the downtime between consultations/procedures.

Hemodynamics in the Valsalva sinuses after transcatheter aortic valve implantation (TAVI).

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess, in vitro, the hemodynamic modifications produced by transcatheter valves in the Valsalva sinuses, by mean of phase-resolved particle image velocimetry (PIV) measurements. METHODS: Flow measurements were performed on a glass mock aortic root that included three polymeric valve leaflets, before and after the implantation of a Medtronic CoreValve device and of an Edwards SAPIEN valve. All experiments were carried out in a hydro-mechanical cardiovascular pulse duplicator system (Vivitro Superpump System SP3891) that reproduced physiologically equivalent pressures and flow rates conforming to the requirements of the standard ISO 5840:2005. The flow dynamics, before and after implantation of the two prosthetic devices, was characterized on the basis of phase-resolved velocity field and viscous shear rate measurements. RESULTS: Direct comparison indicated that both transcatheter valves determined a significant variation of flow during the early stages of valve opening and during valve closure. In general, the presence of the two valve implants significantly reduced the flow activity in the Valsalva sinuses, promoting regions of stagnation at their base. CONCLUSION: The reduction in flow in the Valsalva sinuses could be associated with the higher incidence of ischemic events reported after transcatheter heart valve implantation.

Experimental Validation of Enhanced Magnetic Resonance Imaging (EMRI) Using Particle Image Velocimetry (PIV).

Flow-sensitive four-dimensional Cardiovascular Magnetic Resonance Imaging (4D Flow CMR) has increasingly been utilised to characterise patients' blood flow, in association with patiens' state of health and disease, even though spatial and temporal resolutions still constitute a limit. Computational fluid dynamics (CFD) is a powerful tool that could expand these information and, if integrated with experimentally-obtained velocity fields, would enable to derive a large variety of the flow descriptors of interest. However, the accuracy of the flow parameters is highly influenced by the quality of the input data such as the anatomical model and boundary conditions typically derived from medical images including 4D Flow CMR. We previously proposed a novel approach in which 4D Flow CMR and CFD velocity fields are integrated to obtain an Enhanced 4D Flow CMR (EMRI), allowing to overcome the spatial-resolution limitation of 4D Flow CMR, and enable an accurate quantification of flow. In this paper, the proposed approach is validated in a U bend channel, an idealised model of the human aortic arch. The flow patterns were studied with 4D Flow CMR, CFD and EMRI, and compared with high resolution 2D PIV experiments obtained in pulsatile conditions. The main strengths and limitations of 4D Flow CMR and CFD were illustrated by exploiting the accuracy of PIV by comparing against PIV velocity fields. EMRI flow patterns showed a better qualitative and quantitative agreement with PIV results than the other techniques. EMRI enables to overcome the experimental limitations of MRI-based velocity measurements and the modelling simplifications of CFD, allowing an accurate prediction of complex flow patterns observed experimentally, while satisfying mass and momentum balance equations.

Advances in human mesenchymal stromal cell-based therapies - Towards an integrated biological and engineering approach.

Recent advances of stem cell-based therapies in clinical trials have raised the need for large-scale manufacturing platforms that can supply clinically relevant doses to meet an increasing demand. Promising results have been reported using stirred-tank bioreactors, where human Mesenchymal Stromal Cells (hMSCs) were cultured in suspension on microcarriers (MCs), although the formation of microcarrier-cell-aggregates might still limit mass transfer and determine a heterogeneous distribution of hMSCs. A variety of MCs, bioreactor-impeller configurations, and agitation conditions have been established in an attempt to overcome the trade-off of ensuring good suspension while keeping the stresses to a minimum. While understanding and controlling the fluid flow environment of bioreactors has been initially under-appreciated, it has recently gained in popularity in the mission of providing ideal culture environments across different scales. This review article aims to provide a comprehensive overview of how rigorous engineering characterisation studies improved the outcome of biological process development and scale-up efforts. Reconciling these two disciplines is crucial to propose tailored bioprocessing solutions that can provide improved growth environments across a range of scales for the allogeneic cell therapies of the future.

Does transcatheter aortic valve alignment matter?

Objective: This study investigates the effect of transcatheter aortic valve (TAV) angular alignment on the postprocedure haemodynamics. TAV implantation has emerged as an effective alternative to surgery when treating valve dysfunction. However, the benefit of avoiding surgery is paid back by the inability to remove the native diseased leaflets and accurately position the device in relation to the aortic root, and the literature has shown the root anatomy and substitute position can play an essential role on valve function. Methods: A commercial TAV was placed in a silicone mock aortic root in vitro, including mock native leaflets, and either aligned commissure-to-commissure or in maximum misalignment. Haemodynamic performance data at various stroke volumes were measured, and Particle Image Velocimetry analysis was performed at a typical stroke volume for rest conditions. The two configurations were also studied without mock native leaflets, for comparison with previous in vitro studies. Results: Haemodynamic performance data were similar for all configurations. However, imaging analysis indicated that valve misalignment resulted in the central jet flow not extending to the root wall in the native commissures' vicinity, replaced by a low shear flow, and a reduction of upper sinus flow of 40%, increasing flow stagnation in the sinus. Conclusions: TAV misalignment did not result in a significant change in valve hydrodynamic performance, but determined some change in the fluid flow patterns, which may promote pathological scenarios, such as increased thrombogenicity of blood flow within the sinuses of Valsalva, and plaque formation around the lumen of the sinotubular junction.

Validation and Extension of a Fluid-Structure Interaction Model of the Healthy Aortic Valve.

PURPOSE: The understanding of the optimum function of the healthy aortic valve is essential in interpreting the effect of pathologies in the region, and in devising effective treatments to restore the physiological functions. Still, there is no consensus on the operating mechanism that regulates the valve opening and closing dynamics. The aim of this study is to develop a numerical model that can support a better comprehension of the valve function and serve as a reference to identify the changes produced by specific pathologies and treatments. METHODS: A numerical model was developed and adapted to accurately replicate the conditions of a previous in vitro investigation into aortic valve dynamics, performed by means of particle image velocimetry (PIV). The resulting velocity fields of the two analyses were qualitatively and quantitatively compared to validate the numerical model. In order to simulate more physiological operating conditions, this was then modified to overcome the main limitations of the experimental setup, such as the presence of a supporting stent and the non-physiological properties of the fluid and vessels. RESULTS: The velocity fields of the initial model resulted in good agreement with those obtained from the PIV, with similar flow structures and about 90% of the computed velocities after valve opening within the standard deviation of the equivalent velocity measurements of the in vitro model. Once the experimental limitations were removed from the model, the valve opening dynamics changed substantially, with the leaflets opening into the sinuses to a much greater extent, enlarging the effective orifice area by 11%, and reducing greatly the vortical structures previously observed in proximity of the Valsalva sinuses wall. CONCLUSIONS: The study suggests a new operating mechanism for the healthy aortic valve leaflets considerably different from what reported in the literature to date and largely more efficient in terms of hydrodynamic performance. This work also confirms the crucial role that numerical approaches, complemented with experimental findings, can play in overcoming some of the limitations inherent in experimental techniques, supporting the full understanding of complex physiological phenomena.

Impact of hydrodynamics on iPSC-derived cardiomyocyte differentiation processes.

Cardiomyocytes (CMs), derived from pluripotent stem cells (PSCs), have the potential to be used in cardiac repair. Addition of physical cues, such as electrical and mechanical stimulations, have proven to significantly effect morphology, density, cardiogenesis, maturity and functionality of differentiated CMs. This work combines rigorous fluid dynamics investigation and flow frequency analysis with iPSC differentiation experiments to identify and quantify the flow characteristics leading to a significant increase of differentiation yield. This is towards a better understanding of the physical relationship between frequency modulation and embryoid bodies suspension, and the development of dimensionless correlations applicable at larger scales. Laser Doppler Anemometry and Fast Fourier Transform analysis were used to identify characteristic flow frequencies under different agitation modes. Intermittent agitation resulted in a pattern of low intensity frequencies at reactor scale that could be controlled by varying three identified time components: rotational speed, interval and dwell times. A proof of concept biological study was undertaken, tuning the hydrodynamic environment through variation of dwell time based on the engineering study findings and a significant improvement in CM yield was obtained. This work introduces the concept of fine-tuning the physical hydrodynamic cues within a three-dimensional flow system to improve cardiomyocyte differentiation of iPSC.

Transcatheter aortic valves produce unphysiological flows which may contribute to thromboembolic events: An in-vitro study.

PURPOSE: Transcatheter aortic valve implantation (TAVI) has been associated with large incidence of ischemic events, whose sources are still unclear. In fact, sub-acute complications cannot be directly related to the severity of the calcification in the host tissues, nor with catheter manipulation during the implant. A potential cause could be local flow perturbations introduced by the implantation approach, resulting in thrombo-embolic consequences. In particular, contrary to the surgical approach, TAVI preserves the presence of the native leaflets, which are expanded in the paravalvular space inside the Valsalva sinuses. The purpose of this study is to verify if this configuration can determine hemodynamic variations which may promote blood cell aggregation and thrombus formation. METHODS: The study was performed in vitro, on idealized models of the patient anatomy before and after TAVI, reproducing a range of physiological operating conditions on a pulse duplicator. The fluid dynamics in the Valsalva sinuses was analyzed and characterized using phase resolved Particle Image Velocimetry. RESULTS: Comparison of the flow downstream the valve clearly indicated major alterations in the fluid mechanics after TAVI, characterized by unphysiological conditions associated with extended stagnation zones at the base of the sinuses. CONCLUSION: The prolonged stasis observed in the Valsalva sinuses for the configuration modelling the presence of transcatheter aortic valves provides a fluid dynamic environment favourable for red blood cell aggregation and thrombus formation, which may justify some of the recently reported thromboembolic and ischemic events. This suggests the adoption of anticoagulation therapies following TAVI, and some caution in the patients׳ selection.

Physiological vortices in the sinuses of Valsalva: An in vitro approach for bio-prosthetic valves.

PURPOSE: The physiological flow dynamics within the Valsalva sinuses, in terms of global and local parameters, are still not fully understood. This study attempts to identify the physiological conditions as closely as possible, and to give an explanation of the different and sometime contradictory results in literature. METHODS: An in vitro approach was implemented for testing porcine bio-prosthetic valves operating within different aortic root configurations. All tests were performed on a pulse duplicator, under physiological pressure and flow conditions. The fluid dynamics established in the various cases were analysed by means of 2D Particle Image Velocimetry, and related with the achieved hydrodynamic performance. RESULTS: Each configuration is associated with substantially different flow dynamics, which significantly affects the valve performance. The configuration most closely replicating healthy native anatomy was characterised by the best hemodynamic performance, and any mismatch in size and position between the valve and the root produced substantial modification of the fluid dynamics downstream of the valve, hindering the hydrodynamic performance of the system. The worst conditions were observed for a configuration characterised by the total absence of the Valsalva sinuses. CONCLUSION: This study provides an explanation for the different vortical structures described in the literature downstream of bioprosthetic valves, enlightening the experimental complications in valve testing. Most importantly, the results clearly identify the fluid mechanisms promoted by the Valsalva sinuses to enhance the ejection and closing phases, and this study exposes the importance of an optimal integration of the valve and root, to operate as a single system.