Generation of induced alveolar assembloids with functional alveolar-like macrophages

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 9, 2025

Within the human lung, interactions between alveolar epithelial cells and resident macrophages shape lung development function in both health disease. To study these processes, we develop a co-culture system combining pluripotent stem cell-derived organoids induced to create functional environment, termed assembloids. Using single-cell RNA sequencing analyses, identify type 2-like producing GM-CSF, which supports macrophage tissue adaptation, macrophage-like that secrete interleukin-1β interleukin-6, express surfactant metabolism genes, demonstrate core immune functions. In response injury, efficiently eliminate damaged absorb oxidized lipids. Exposure bacterial components or infection with Mycobacterium tuberculosis reveals assembloids replicate key aspects of respiratory defense. These findings highlight potential as platform investigate development, immunity,

Language: Английский

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Nanotechnology-Based Drug Delivery Systems to Control Bacterial-Biofilm-Associated Lung Infections

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(11), P. 2582 - 2582

Published: Nov. 3, 2023

Airway mucus dysfunction and impaired immunological defenses are hallmarks of several lung diseases, including asthma, cystic fibrosis, chronic obstructive pulmonary mostly causative factors in bacterial-biofilm-associated respiratory tract infections. Bacteria residing within the biofilm architecture pose a complex challenge clinical settings due to their increased tolerance currently available antibiotics host immune responses, resulting infections with high recalcitrance rates morbidity mortality. To address these unmet needs, potential anti-biofilm therapeutic strategies being developed effectively control bacterial biofilm. This review focuses on recent advances development application nanoparticulate drug delivery systems for treatment biofilm-associated infections, especially addressing barriers concern accessibility various types nanoparticles used combat biofilms. Understanding obstacles facing biofilms nanoparticle-based approaches combatting may encourage researchers explore promising modalities

Language: Английский

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Streamlining the Highly Reproducible Fabrication of Fibrous Biomedical Specimens toward Standardization and High Throughput

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 14(4)

Published: Dec. 15, 2024

Soft nano- and microfiber-based polymer scaffolds bear enormous potential for their use in cell culture tissue engineering since they mimic natural collagen structures may thus serve as biomimetic adhesive substrates. They have, however, so far been restricted to small-scale production research labs with high batch-to-batch variation. are commonly produced via electrospinning or melt electrowriting delicate nature poses obstacles detachment, storage, transportation. This study focuses on overcoming challenges the throughput practical handling, introducing new methods reproducibly prepare such suitable quantitative applications. Attention is given seamless handling transfer of samples without compromising structural integrity. Challenges detaching fibers damage well transport addressed. Cell studies demonstrate methodological advantages, emphasizing standardized testing biological readouts these fiber materials. The developed applicable across various approaches can essentially contribute utilization laboratory commercial

Language: Английский

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A ventilated perfused lung model platform to dissect the response of the lungs to viral infection

Trends in biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Comparison of submerged and air liquid interface exposure: limitations and differences in the toxicological effects evaluated in bronchial epithelial cells

Environmental Research, Journal Year: 2025, Volume and Issue: 279, P. 121856 - 121856

Published: May 14, 2025

Language: Английский

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Dynamic 3D in vitro lung models: applications of inorganic nanoparticles for model development and characterization

Nanoscale, Journal Year: 2024, Volume and Issue: 16(23), P. 10880 - 10900

Published: Jan. 1, 2024

Being a vital organ exposed to the external environment, lung is susceptible plethora of pathogens and pollutants. This reflected in high incidences chronic respiratory diseases, which remain leading cause mortality world-wide pose persistent global burden. It thus paramount importance improve our understanding these pathologies provide better therapeutic options. necessitates development representative physiologically relevant vitro models. Advances bioengineering have enabled sophisticated models that not only capture three-dimensional architecture cellular environment but also incorporate dynamics local biophysical stimuli. However, such complex require novel approaches reliable characterization. Within this review we explore how 3D bioprinting nanoparticles can serve as multifaceted tools develop dynamic 4D printed facilitate their characterization context pulmonary fibrosis breast cancer metastasis.

Language: Английский

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A bionic controllable strain membrane for cell stretching at air–liquid interface inspired by papercutting

International Journal of Extreme Manufacturing, Journal Year: 2023, Volume and Issue: 5(4), P. 045502 - 045502

Published: Aug. 11, 2023

Abstract Lung diseases associated with alveoli, such as acute respiratory distress syndrome, have posed a long-term threat to human health. However, an in vitro model capable of simulating different deformations the alveoli and suitable material for mimicking basement membrane are currently lacking. Here, we present innovative biomimetic controllable strain (BCSM) at air–liquid interface (ALI) reconstruct alveolar respiration. The BCSM consists high-precision three-dimensional printing melt-electrowritten polycaprolactone (PCL) mesh, coated hydrogel substrate—to simulate important functions (such stiffness, porosity, wettability, ALI) microenvironments, seeded pulmonary epithelial cells vascular endothelial on either side, respectively. Inspired by papercutting, was fabricated plane while it operated three dimensions. A series topological structure designed control various local-area strain, varied deformation. Lopinavir/ritonavir could reduce Lamin expression under over-stretch condition, which might be effective preventing ventilator-induced lung injury. lung-unit has broader application prospects alveoli-related research future, drug toxicology metabolism.

Language: Английский

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Breathing-induced stretch enhances the efficacy of an inhaled and orally delivered anti-fibrosis drug in vitro

Journal of Drug Delivery Science and Technology, Journal Year: 2023, Volume and Issue: 82, P. 104316 - 104316

Published: Feb. 25, 2023

Mechanical forces, which are crucial for most downstream signaling pathways in lung (patho-)physiology, may also regulate the efficacy of drugs. We investigated role mechanical forces on effectiveness inhaled and systemic (oral) administration an anti-fibrosis drug. established induced triple coculture fibrosis model a tight alveolar endothelial-epithelial barrier combined with pro-fibrotically stimulated primary fibroblasts derived from healthy donors compared it to analogous idiopathic pulmonary (IPF) patients (innate IPF model). The 3D vitro models were biomimetic, stretchable basement (BETA) membrane cultured at air-liquid interface (ALI). These treated FDA-approved drug (oral aerosolized application Nintedanib) under static dynamic culture conditions – including cyclic stretch medium-flow shear stress leveraging our advanced millifluidic CIVIC mini-lung technology. Fibrosis markers characterized by protein immunofluorescence analysis supplemented real-time measurement compliance as functional assay. Nintedanib shows more potent anti-inflammatory (IL1β, IL-6, IL8) anti-fibrotic (αSMA, soluble deposited (type I) collagen, compliance) effects both delivery methods. Mechanotransduction enhanced restoration phenotypes after delivery, indicated surfactant C Yes-associated levels. Our findings suggest that plays Nintedanib. Albeit Nintedanib's potency routes is similar, has lower off-target dose fraction than oral application. Thus, showed superior therapeutic index

Language: Английский

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Fabrication Strategies for Bioinspired and Functional Lung‐on‐Chips

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(46)

Published: Aug. 16, 2024

Abstract Lung‐on‐chips (LoCs) are advanced microsystems designed to culture pulmonary cells under physiologically relevant conditions, including air–liquid interface, cell stretch, and shear stress. As the most promising preclinical models, LoCs aimed reduce ultimately replace conventional ineffective animal studies. Biomimetic functional lead more translational studies that effectively address unmet needs across therapeutic areas. A variety of cell‐ scaffold‐based techniques employed establish biomimetic models closely resemble their in vivo counterparts, which is a challenging yet critical aspect LoCs. Herein, challenges encountered discussed, future perspectives toward higher biomimicry using biofabrication approaches explored.

Language: Английский

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Transwell‐Based Microfluidic Platform for High‐Resolution Imaging of Airway Tissues

Advanced Materials Technologies, Journal Year: 2024, Volume and Issue: 9(20)

Published: July 10, 2024

Abstract Transwell‐based airway models have become increasingly important in studying the effects of respiratory diseases and drug treatment at air–liquid interface lung epithelial barrier. However, underlying mechanisms tissue cell level often remain unclear, as transwell inserts feature limited live‐cell imaging compatibility. Here, a novel microfluidic platform is reported for cultivation transwell‐based tissues providing possibility to alternate between liquid–liquid interfaces. While recapitulates physiological conditions model, enables live high spatiotemporal resolution. The plastics‐based insertion recuperation inserts, which allows analysis under standardized well plate conditions. device used monitor infections Pseudomonas aeruginosa human stem‐cell‐derived bronchial tissue. progression P. infection real‐time resolution continuously imaged, provides insights into bacterial spreading invasion on apical surface, breaching destruction over time. culture system powerful tool visualize elucidate key processes developing facilitate testing development.

Language: Английский

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