Development of pH-Sensitive Magnetoliposomes Containing Shape Anisotropic Nanoparticles for Potential Application in Combined Cancer Therapy.

Late diagnosis and systemic toxicity associated with conventional treatments make oncological therapy significantly difficult. In this context, nanomedicine emerges as a new approach in the prevention, diagnosis and treatment of cancer. In this work, pH-sensitive solid magnetoliposomes (SMLs) were developed for controlled release of the chemotherapeutic drug doxorubicin (DOX). Shape anisotropic magnetic nanoparticles of magnesium ferrite with partial substitution by calcium (Mg0.75Ca0.25Fe2O4) were synthesized, with and without calcination, and their structural, morphological and magnetic properties were investigated. Their superparamagnetic properties were evaluated and heating capabilities proven, either by exposure to an alternating magnetic field (AMF) (magnetic hyperthermia) or by irradiation with near-infrared (NIR) light (photothermia). The Mg0.75Ca0.25Fe2O4 calcined nanoparticles were selected to integrate the SMLs, surrounded by a lipid bilayer of DOPE:Ch:CHEMS (45:45:10). DOX was encapsulated in the nanosystems with an efficiency above 98%. DOX release assays showed a much more efficient release of the drug at pH = 5 compared to the release kinetics at physiological pH. By subjecting tumor cells to DOX-loaded SMLs, cell viability was significantly reduced, confirming that they can release the encapsulated drug. These results point to the development of efficient pH-sensitive nanocarriers, suitable for a synergistic action in cancer therapy with magnetic targeting, stimulus-controlled drug delivery and dual hyperthermia (magnetic and plasmonic) therapy.

Editorial for the Special Issue on Micro/Nanofluidic and Lab-on-a-Chip Devices for Biomedical Applications.

Micro/Nanofluidic and lab-on-a-chip devices have been increasingly used in biomedical research [...].

Diagnosis Methods for COVID-19: A Systematic Review.

At the end of 2019, the coronavirus appeared and spread extremely rapidly, causing millions of infections and deaths worldwide, and becoming a global pandemic. For this reason, it became urgent and essential to find adequate tests for an accurate and fast diagnosis of this disease. In the present study, a systematic review was performed in order to provide an overview of the COVID-19 diagnosis methods and tests already available, as well as their evolution in recent months. For this purpose, the Science Direct, PubMed, and Scopus databases were used to collect the data and three authors independently screened the references, extracted the main information, and assessed the quality of the included studies. After the analysis of the collected data, 34 studies reporting new methods to diagnose COVID-19 were selected. Although RT-PCR is the gold-standard method for COVID-19 diagnosis, it cannot fulfill all the requirements of this pandemic, being limited by the need for highly specialized equipment and personnel to perform the assays, as well as the long time to get the test results. To fulfill the limitations of this method, other alternatives, including biological and imaging analysis methods, also became commonly reported. The comparison of the different diagnosis tests allowed to understand the importance and potential of combining different techniques, not only to improve diagnosis but also for a further understanding of the virus, the disease, and their implications in humans.

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review.

The development of cancer models that rectify the simplicity of monolayer or static cell cultures physiologic microenvironment and, at the same time, replicate the human system more accurately than animal models has been a challenge in biomedical research. Organ-on-a-chip (OoC) devices are a solution that has been explored over the last decade. The combination of microfluidics and cell culture allows the design of a dynamic microenvironment suitable for the evaluation of treatments' efficacy and effects, closer to the response observed in patients. This systematic review sums the studies from the last decade, where OoC with cancer cell cultures were used for drug screening assays. The studies were selected from three databases and analyzed following the research guidelines for systematic reviews proposed by PRISMA. In the selected studies, several types of cancer cells were evaluated, and the majority of treatments tested were standard chemotherapeutic drugs. Some studies reported higher drug resistance of the cultures on the OoC devices than on 2D cultures, which indicates the better resemblance to in vivo conditions of the former. Several studies also included the replication of the microvasculature or the combination of different cell cultures. The presence of vasculature can influence positively or negatively the drug efficacy since it contributes to a greater diffusion of the drug and also oxygen and nutrients. Co-cultures with liver cells contributed to the evaluation of the systemic toxicity of some drugs metabolites. Nevertheless, few studies used patient cells for the drug screening assays.

Computational Simulations in Advanced Microfluidic Devices: A Review.

Numerical simulations have revolutionized research in several engineering areas by contributing to the understanding and improvement of several processes, being biomedical engineering one of them. Due to their potential, computational tools have gained visibility and have been increasingly used by several research groups as a supporting tool for the development of preclinical platforms as they allow studying, in a more detailed and faster way, phenomena that are difficult to study experimentally due to the complexity of biological processes present in these models-namely, heat transfer, shear stresses, diffusion processes, velocity fields, etc. There are several contributions already in the literature, and significant advances have been made in this field of research. This review provides the most recent progress in numerical studies on advanced microfluidic devices, such as organ-on-a-chip (OoC) devices, and how these studies can be helpful in enhancing our insight into the physical processes involved and in developing more effective OoC platforms. In general, it has been noticed that in some cases, the numerical studies performed have limitations that need to be improved, and in the majority of the studies, it is extremely difficult to replicate the data due to the lack of detail around the simulations carried out.

3D Printing Techniques and Their Applications to Organ-on-a-Chip Platforms: A Systematic Review.

Three-dimensional (3D) in vitro models, such as organ-on-a-chip platforms, are an emerging and effective technology that allows the replication of the function of tissues and organs, bridging the gap amid the conventional models based on planar cell cultures or animals and the complex human system. Hence, they have been increasingly used for biomedical research, such as drug discovery and personalized healthcare. A promising strategy for their fabrication is 3D printing, a layer-by-layer fabrication process that allows the construction of complex 3D structures. In contrast, 3D bioprinting, an evolving biofabrication method, focuses on the accurate deposition of hydrogel bioinks loaded with cells to construct tissue-engineered structures. The purpose of the present work is to conduct a systematic review (SR) of the published literature, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, providing a source of information on the evolution of organ-on-a-chip platforms obtained resorting to 3D printing and bioprinting techniques. In the literature search, PubMed, Scopus, and ScienceDirect databases were used, and two authors independently performed the search, study selection, and data extraction. The goal of this SR is to highlight the importance and advantages of using 3D printing techniques in obtaining organ-on-a-chip platforms, and also to identify potential gaps and future perspectives in this research field. Additionally, challenges in integrating sensors in organs-on-chip platforms are briefly investigated and discussed.

Hemodynamic study in 3D printed stenotic coronary artery models: experimental validation and transient simulation.

Atherosclerosis is a progressive disease that can significantly reduce blood supply to vital organs, being one of the main causes of death worldwide. In this work, a numerical and experimental study in 3D printed stenotic coronary arteries, considering both steady and pulsatile blood flow conditions, is presented. The results revealed that a degree of stenosis superior to 50% creates disturbed flows downstream of the contraction, with an accented increase in the wall shear stress measurements at the stenosis throat. Finally, the multiphase mixture was investigated and compared with a single-phase modelling, and only slight differences were observed right after the stenosis throat.

Visualization and Measurements of Blood Cells Flowing in Microfluidic Systems and Blood Rheology: A Personalized Medicine Perspective.

Hemorheological alterations in the majority of metabolic diseases are always connected with blood rheology disturbances, such as the increase of blood and plasma viscosity, cell aggregation enhancement, and reduction of the red blood cells (RBCs) deformability. Thus, the visualizations and measurements of blood cells deformability flowing in microfluidic devices (point-of-care devices) can provide vital information to diagnose early symptoms of blood diseases and consequently to be used as a fast clinical tool for early detection of biomarkers. For instance, RBCs rigidity has been correlated with myocardial infarction, diabetes mellitus, hypertension, among other blood diseases. In order to better understand the blood cells behavior in microfluidic devices, rheological properties analysis is gaining interest by the biomedical committee, since it is strongly dependent on the interactions and mechanical cells proprieties. In addition, the development of blood analogue fluids capable of reproducing the rheological properties of blood and mimic the RBCs behavior at in vitro conditions is crucial for the design, performance and optimization of the microfluidic devices frequently used for personalized medicine. By combining the unique features of the hemorheology and microfluidic technology for single-cell analysis, valuable advances in personalized medicine for new treatments and diagnosis approach can be achieved.

3D Printed Biomodels for Flow Visualization in Stenotic Vessels: An Experimental and Numerical Study.

Atherosclerosis is one of the most serious and common forms of cardiovascular disease and a major cause of death and disability worldwide. It is a multifactorial and complex disease that promoted several hemodynamic studies. Although in vivo studies more accurately represent the physiological conditions, in vitro experiments more reliably control several physiological variables and most adequately validate numerical flow studies. Here, a hemodynamic study in idealized stenotic and healthy coronary arteries is presented by applying both numerical and in vitro approaches through computational fluid dynamics simulations and a high-speed video microscopy technique, respectively. By means of stereolithography 3D printing technology, biomodels with three different resolutions were used to perform experimental flow studies. The results showed that the biomodel printed with a resolution of 50 µm was able to most accurately visualize flow due to its lowest roughness values (Ra = 1.8 µm). The flow experimental results showed a qualitatively good agreement with the blood flow numerical data, providing a clear observation of recirculation regions when the diameter reduction reached 60%.

Thermal comfort assessment of a surgical room through computational fluid dynamics using local PMV index.

BACKGROUND: Studies concerning indoor thermal conditions are very important in defining the satisfactory comfort range in health care facilities. OBJECTIVE: This study focuses on the evaluation of the thermal comfort sensation felt by surgeons and nurses, in an orthopaedic surgical room of a Portuguese hospital. METHODS: Two cases are assessed, with and without the presence of a person. Computational fluid dynamic (CFD) tools were applied for evaluating the predicted mean vote (PMV) index locally. RESULTS: Using average ventilation values to calculate the PMV index does not provide a correct and enough descriptive evaluation of the surgical room thermal environment. As studied for both cases, surgeons feel the environment slightly hotter than nurses. The nurses feel a slightly cold sensation under the air supply diffuser and their neutral comfort zone is located in the air stagnation zones close to the walls, while the surgeons feel the opposite. It was observed that the presence of a person in the room leads to an increase of the PMV index for surgeons and nurses. That goes in line with the empirical knowledge that more persons in a room lead to an increased heat sensation. CONCLUSIONS: The clothing used by both classes, as well as the ventilation conditions, should be revised accordingly to the amount of persons in the room and the type of activity performed.

[Evaluation of the performance of three spacers]. / Avaliação do Desempenho de Três Câmaras de Expansão.

INTRODUCTION: Several aspects are known to influence the drug distribution within the low respiratory tract, with particular emphasis on those related to the inhalation device. The aim of this work was to assess the performance of three spacers in the drug release, and also the quantity of active agent deposited inside these devices. MATERIALS AND METHODS: In order to evaluate the behaviour of particles in suspension delivered through the Ventilan®HFA inhaler coupled to three different spacers (Volumatic®, AeroChamber MAX® and NebuChamber®) the Multistage Liquid Impinger (MSLI) was used, according to the Portuguese Pharmacopoeia. The mass of salbutamol sulphate deposited on the different impinger compartments and inside the spacer was determined by spectrophotometry, with the purpose of determining the percentage of cumulative mass for each spacer, and then the fine particle fraction. The results were compared statistically using a one-way analysis of variance (one-way ANOVA) with a Bonferroni post-hoc test. RESULTS: About 40 to 50% of salbutamol sulphate was found deposited in the body of the three spacers. This deposition was slightly lower for NebuChamber® (average ± standard deviation of 43.8 % ± 11.6 %), in relation to Volumatic® (p=0.351) or AeroChamber MAX® (p=0.115). The fine particle fraction reached values of 28.2 ± 4.1%, 29.6 ± 2.4% and 30.9 ± 6.7% for Volumatic®, AeroChamber MAX® and NebuChamber®, respectively. CONCLUSION: The spacers showed to have similar efficiencies in the delivery of salbutamol sulphate in the last stages, and there was no relation between the results and the spacers characteristics such as volume, shape and material. Therefore, Volumatic® appears to be perfect for hospital use, since its big volume does not constitute a disadvantage, and its lower cost, when compared to the remaining two spacers, represents an advantage of utmost importance for public hospitals.

Development of new spacer device geometry: a CFD study (part I).

Asthma is a widespread disease, affecting more than 300 million individuals. The treatment in children is based upon an administration of a pressurised metered-dose inhaler added with a spacer. The efficiency of drug delivery to the patient is strongly affected by the transient airflow pattern inside the spacer device. This paper presents a computational fluid dynamics (CFD) analysis of airflow inside a commercially available spacer device with wide application. This study, carried out in Fluent™, was the basis of an optimisation procedure developed to improve the geometry of the spacer and develop a more efficient product. The results show that an appropriate control of the boundary layer development, by changing the spacer shape, reduces the length of the recirculation zones and improves the flow. It can be concluded that CFD is a powerful technique that can be successfully applied to optimise the geometry of such medical devices.