Organ-on-a-chip platforms for drug development, cellular toxicity assessment, and disease modeling.

Organs-on-chips (OoCs) or microphysiological platforms are biomimetic systems engineered to emulate organ structures on microfluidic devices for biomedical research. These microdevices can mimic biological environments that enable cell-cell interactions on a small scale by mimicking 3D in vivo microenvironments outside the body. Thus far, numerous single and multiple OoCs that mimic organs have been developed, and they have emerged as forerunners for drug efficacy and cytotoxicity testing.

A comprehensive review on organ-on-chips as powerful preclinical models to study tissue barriers.

In the preclinical stage of drug development, 2D and 3D cell cultures under static conditions followed by animal models are utilized. However, these models are insufficient to recapitulate the complexity of human physiology. With the developing organ-on-chip (OoC) technology in recent years, human physiology and pathophysiology can be modeled better than traditional models.

ICU patient-on-a-chip emulating orchestration of mast cells and cerebral organoids in neuroinflammation.

Propofol and midazolam are the current standard of care for prolonged sedation in Intensive Care Units (ICUs). However, the effects and mechanism of these sedatives in brain tissue are unclear. Herein, the development of an ICU patient-on-a-chip platform to elucidate those effects is reported.

Comprehensive analysis of resilience of human airway epithelial barrier against short-term PM2.5 inorganic dust exposure using in vitro microfluidic chip and ex vivo human airway models.

Background And Objective: The updated World Health Organization (WHO) air quality guideline recommends an annual mean concentration of fine particulate matter (PM2.5) not exceeding 5 or 15 μg/m in the short-term (24 h) for no more than 3-4 days annually. However, more than 90% of the global population is currently exposed to daily concentrations surpassing these limits, especially during extreme weather conditions and due to transboundary dust transport influenced by climate change.

Organotypic lung tissue culture as a preclinical model to study host- influenza A viral infection: A case for repurposing of nafamostat mesylate.

Reliable and effective models for recapitulation of host-pathogen interactions are imperative for the discovery of potential therapeutics. Ex vivo models can fulfill these requirements as the multicellular native environment in the tissue is preserved and be utilized for toxicology, vaccine, infection and drug efficacy studies due to the presence of immune cells. Drug repurposing involves the identification of new applications for already approved drugs that are not related to the prime medical indication and emerged as a strategy to cope with slow pace of drug discovery due to high costs and necessary phases to reach the patients.

Receptor mediated targeting of EGF-conjugated alginate-PAMAM nanoparticles to lung adenocarcinoma: 2D/3D in vitro and in vivo evaluation.

Carboplatin (cis-diamine (1,1-cyclobutandicarboxylaso)‑platinum (II)) is a second-generation antineoplastic drug, which is widely used for chemotherapy of lung, colon, breast, cervix, testicular and digestive system cancers. Although preferred over cisplatin due to the lower incidence of nephrotoxicity and ototoxicity, efficient carboplatin delivery remains as a major challenge. In this study, carboplatin loaded alginate- poly(amidoamine) (PAMAM) hybrid nanoparticles (CAPs) with mean sizes of 192.

Humanized brain organoids-on-chip integrated with sensors for screening neuronal activity and neurotoxicity.

The complex structure and function of the human central nervous system that develops from the neural tube made in vitro modeling quite challenging until the discovery of brain organoids. Human-induced pluripotent stem cells-derived brain organoids offer recapitulation of the features of early human neurodevelopment in vitro, including the generation, proliferation, and differentiation into mature neurons and micro-macroglial cells, as well as the complex interactions among these diverse cell types of the developing brain. Recent advancements in brain organoids, microfluidic systems, real-time sensing technologies, and their cutting-edge integrated use provide excellent models and tools for emulation of fundamental neurodevelopmental processes, the pathology of neurological disorders, personalized transplantation therapy, and high-throughput neurotoxicity testing by bridging the gap between two-dimensional models and the complex three-dimensional environment in vivo.

Comprehensive Transcriptomic Investigation of Rett Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent Stem Cells to Neurons with Implications for Enriched Pathways.

Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder that has no cure apart from symptomatic treatments. While intense research efforts are required to fulfill this unmet need, the fundamental challenge is to obtain sufficient patient data. In this study, we used human transcriptomic data of four different sample types from RTT patients including induced pluripotent stem cells, differentiated neural progenitor cells, differentiated neurons, and postmortem brain tissues with an increasing in vivo-like complexity to unveil specific trends in gene expressions across the samples.

Differentiation of Neurons, Astrocytes, Oligodendrocytes and Microglia From Human Induced Pluripotent Stem Cells to Form Neural Tissue-On-Chip: A Neuroinflammation Model to Evaluate the Therapeutic Potential of Extracellular Vesicles Derived from Mesenchymal Stem Cells.

Advances in stem cell (SC) technology allow the generation of cellular models that recapitulate the histological, molecular and physiological properties of humanized in vitro three dimensional (3D) models, as well as production of cell-derived therapeutics such as extracellular vesicles (EVs). Improvements in organ-on-chip platforms and human induced pluripotent stem cells (hiPSCs) derived neural/glial cells provide unprecedented systems for studying 3D personalized neural tissue modeling with easy setup and fast output. Here, we highlight the key points in differentiation procedures for neurons, astrocytes, oligodendrocytes and microglia from single origin hiPSCs.

Spatio-temporal dynamics enhance cellular diversity, neuronal function and further maturation of human cerebral organoids.

The bioengineerined and whole matured human brain organoids stand as highly valuable three-dimensional in vitro brain-mimetic models to recapitulate in vivo brain development, neurodevelopmental and neurodegenerative diseases. Various instructive signals affecting multiple biological processes including morphogenesis, developmental stages, cell fate transitions, cell migration, stem cell function and immune responses have been employed for generation of physiologically functional cerebral organoids. However, the current approaches for maturation require improvement for highly harvestable and functional cerebral organoids with reduced batch-to-batch variabilities.

Biosensor integrated brain-on-a-chip platforms: Progress and prospects in clinical translation.

Because of the brain's complexity, developing effective treatments for neurological disorders is a formidable challenge. Research efforts to this end are advancing as in vitro systems have reached the point that they can imitate critical components of the brain's structure and function. Brain-on-a-chip (BoC) was first used for microfluidics-based systems with small synthetic tissues but has expanded recently to include in vitro simulation of the central nervous system (CNS).

Essential Oil and Supercritical Carbon Dioxide Extract of Grapefruit Peels Formulated for Infections: Evaluation by an Model to Study Fungal-Host Interactions.

Resistance to currently available antifungal agents raises the need to develop alternative remedies. is the most common opportunistic pathogenic fungus of humans, colonizing in the genital and intestinal mucosa, skin, and oral-nasal cavity and reducing quality of life. Herein, essential oil from grapefruit () peels was obtained by hydrodistillation, and the remaining plant material was sequentially subjected to supercritical carbon dioxide (SC-CO) extraction to determine the conditions for maximizing phenolic compounds.

Aligned with sustainable development goals: microwave extraction of astaxanthin from wet algae and selective cytotoxic effect of the extract on lung cancer cells.

Astaxanthin is one of the most attractive carotenoid in the cosmetic, food, pharmaceutical, and aquaculture industries due to its strong bioactive properties. Among the various sources, several algae species are considered as rich sources of astaxanthin. Downstream processing of algae involves the majority of the total processing costs.

A drug-responsive multicellular human spheroid model to recapitulate drug-induced pulmonary fibrosis.

Associated with a high mortality rate, pulmonary fibrosis (PF) is the end stage of several interstitial lung diseases. Although many factors are linked to PF progression, initiation of the fibrotic process remains to be studied. Current research focused on generating new strategies to gain a better understanding of the underlying disease mechanism as the animal models remain insufficient to reflect human physiology.

Bilayered laponite/alginate-poly(acrylamide) composite hydrogel for osteochondral injuries enhances macrophage polarization: An in vivo study.

Addressing osteochondral defects, the objective of current study was to synthesize bilayered hydrogel, where the cartilage layer was formed by alginate (Alg)-polyacrylamide (PAAm) with and without the addition of TGF-β3 and bone layer by laponite XLS/Alg-PAAm and characterize by in vitro and in vivo experiments. Exceeding the mechanical strength of Alg-PAAm (32.95 ± 1.

Decellularised extracellular matrix-based biomaterials for repair and regeneration of central nervous system.

The central nervous system (CNS), consisting of the brain and spinal cord, regulates the mind and functions of the organs. CNS diseases, leading to changes in neurological functions in corresponding sites and causing long-term disability, represent one of the major public health issues with significant clinical and economic burdens worldwide. In particular, the abnormal changes in the extracellular matrix under various disease conditions have been demonstrated as one of the main factors that can alter normal cell function and reduce the neuroregeneration potential in damaged tissue.

Supercritical carbon dioxide dried double layer laponite XLS and alginate/polyacrylamide construct and immune response.

Fabrication of immunocompatible tissue constructs for bone-cartilage defect regeneration is of prime importance. In this study, a double layer hydrogel was successfully synthesized, where alginate/polyacrylamide were formulated to represent cartilage layer (5-10 % (w/w) total polymer ratio) and laponite XLS (2-5-8% (w/w))/alginate/polyacrylamide formed bone layer. Hydrogels were dried by supercritical CO at 100 and 200 bar, 45 °C, 5 g/min CO flow rate for 2 h.

Continuous Microfluidic Production of Citrem-Phosphatidylcholine Nano-Self-Assemblies for Thymoquinone Delivery.

Lamellar and non-lamellar liquid crystalline nanodispersions, including liposomes, cubosomes, and hexosomes are attractive platforms for drug delivery, bio-imaging, and related pharmaceutical applications. As compared to liposomes, there is a modest number of reports on the continuous production of cubosomes and hexosomes. Using a binary lipid mixture of citrem and soy phosphatidylcholine (SPC), we describe the continuous production of nanocarriers for delivering thymoquinone (TQ, a substance with various therapeutic potentials) by employing a commercial microfluidic hydrodynamic flow-focusing chip.

Lung carcinoma spheroids embedded in a microfluidic platform.

Unlabelled: Three-dimensional (3D) spheroid cell cultures are excellent models used in cancer biology research and drug screening. The objective of this study was to develop a lung carcinoma spheroid based microfluidic platform with perfusion function to mimic lung cancer pathology and investigate the effect of a potential drug molecule, panaxatriol. Spheroids were successfully formed on agar microtissue molds at the end of 10 days, reaching an average diameter of about 317.

Antimicrobial and wound healing properties of cotton fabrics functionalized with oil-in-water emulsions containing bark extract and Pycnogenol® for biomedical applications.

Topical formulations containing 1-2% of bark extract and Pycnogenol® have been prepared to investigate the effect of flavonoids on the stability of O/W emulsions, which were subjected to physicochemical and thermal stability tests. The formulations have been applied to cotton fabrics to evaluate antimicrobial properties against and . Furthermore, prepared cotton fabrics have been tested on keratinocytes seeded in cell culture inserts for wound healing.

Erratum: "Human lung-on-chips: Advanced systems for respiratory virus models and assessment of immune response" [Biomicrofluidics 15, 021501 (2021)].

[This corrects the article DOI: 10.1063/5.0038924.

Synthesis of Resveratrol Loaded Hybrid Silica-PAMAM Dendrimer Nanoparticles With Emphases on Inducible Nitric Oxide Synthase and Cytotoxicity.

Resveratrol is a naturally occurring polyphenolic compound exhibiting therapeutic activities. However, the stability can be altered by UV light, pH and changes in temperature. Encapsulation would be an ideal strategy to improve the stability and bioavailability.

Development of an Integrated Optical Sensor for Determination of β-Hydroxybutyrate Within the Microplatform.

Ketone bodies (acetoacetate, beta-hydroxybutyrate (βHB), acetone) are generated as a result of fatty acid oxidation in the liver and exist at low concentrations in urine and blood. Elevated concentrations can indicate health problems such as diabetes, childhood hypoglycemia, alcohol, or salicylate poisoning. Development of portable and cost-effective bedside point-of-care (POC) tests to detect such compounds can help to reduce the risk of disease progression.

Human lung-on-chips: Advanced systems for respiratory virus models and assessment of immune response.

Respiratory viral infections are leading causes of death worldwide. A number of human respiratory viruses circulate in all age groups and adapt to person-to-person transmission. It is vital to understand how these viruses infect the host and how the host responds to prevent infection and onset of disease.

Advances in microfluidic synthesis and coupling with synchrotron SAXS for continuous production and real-time structural characterization of nano-self-assemblies.

Microfluidic platforms have become highly attractive tools for synthesis of nanoparticles, including lipid nano-self-assemblies, owing to unique features and at least three important aspects inherent to miniaturized micro-devices. Firstly, the fluids flow under controlled conditions in the microchannels, providing well-defined flow profiles and shorter diffusion lengths that play important roles in enhancing the continuous production of lipid and polymer nanoparticles with relatively narrow size distributions. Secondly, various geometries adapted to microfluidic device designs can be utilized for enhancing the colloidal stability of nanoparticles and improving their drug loading.