Sex-stratified osteochondral organ-on-chip model reveals sex-specific responses to inflammatory stimulation

Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101728 - 101728

Published: April 1, 2025

Osteoarthritis (OA) is a musculoskeletal degenerative disease characterized by alterations in cartilage and subchondral bone leading to impaired joint function. OA disproportionally affects females more than males, yet the molecular mechanisms underlying these biological sex differences remain elusive. Current therapeutic strategies halt progression of are still lacking, part due limited predictive potential standard models which often do not account for disparities. Herein, an organ-on-chip microfluidic platform was developed model osteochondral unit, composed adjacent culture chambers, capture sex-specific hallmarks OA. Sex-stratified human primary chondrocytes osteoblasts were compartmentalized within biomimetic hydrogels emulating bone-cartilage interface, subjected inflammatory triggers mimic onset We confirmed that interleukin-1β Tumor Necrosis Factor-α stimulation triggered upregulation pro-inflammatory cytokines matrix metalloproteinases related genes all donors, with marginal trends increased expression female cells. In addition, metabolic labeling coupled confocal imaging revealed modulated extracellular deposition fashion. Not only but also remodeling altered upon inflammation, significant reduction stiffness both compartments. Overall, sex-stratified unit on-chips offer novel insights into cellular responses insults, demonstrating importance incorporating stratification emergent models. Thus, this provides physiologically relevant 3D microenvironment further investigate drivers OA, paving way targeted therapies.

Language: Английский

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Classical and Innovative Evidence for Therapeutic Strategies in Retinal Dysfunctions

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2124 - 2124

Published: Feb. 9, 2024

The human retina is a complex anatomical structure that has no regenerative capacity. pathogenesis of most retinopathies can be attributed to inflammation, with the activation inflammasome protein platform, and impact oxidative stress on regulation apoptosis autophagy/mitophagy in retinal cells. In recent years, new therapeutic approaches treat have been investigated. Experimental data suggest secretome mesenchymal cells could reduce stress, autophagy, cells, turn, latter induce changes Other studies evidenced noncoding (nc)RNAs might targets for retinopathy treatment novel disease biomarkers since correlation found between ncRNA levels retinopathies. A field explore interaction observed ocular intestinal microbiota; indeed, findings shown alteration gut microbiota seems linked diseases, suggesting gut-eye axis. To therapeutical strategies retinopathies, it important use proper models mimic complexity retina. this context, organoids represent good model study pathophysiology

Language: Английский

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Toward Functional Biointerfaces with Origami‐on‐a‐Chip

Advanced Intelligent Systems, Journal Year: 2024, Volume and Issue: 6(9)

Published: June 19, 2024

Studying the behavior of electroactive cells, such as firing dynamics and chemical secretion, is crucial for developing human disease models therapeutics. Following recent advances in cell culture technology, traditional monolayers are optimized to resemble more 3D, organ‐like structures. The biological electrochemical complexity these structures requires devices with adaptive shapes novel features, precise electrophysiological mapping stimulation case brain‐ heart‐derived tissues. However, conventional organ‐on‐chip platforms often fall short, they do not recreate native environment cells lack functional interfaces necessary long‐term monitoring. Origami‐on‐a‐chip offer a solution this problem, can flexibly adapt structure desired sample be integrated components enabled by chosen materials. In review, evolution origami‐on‐a‐chip biointerfaces discussed, emphasizing folding stimuli, materials, critical findings. prospects, microfluidic integration, tissue engineering scaffolds, multi‐organoid networks included, allowing patient‐specific diagnoses therapies through computational vitro modeling.

Language: Английский

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Embracing sex-specific differences in engineered kidney models for enhanced biological understanding of kidney function

Biology of Sex Differences, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 2, 2024

Abstract In vitro models serve as indispensable tools for advancing our understanding of biological processes, elucidating disease mechanisms, and establishing screening platforms drug discovery. Kidneys play an instrumental role in the transport elimination drugs toxins. Nevertheless, despite well-documented inter-individual variability kidney function multifaceted nature renal diseases—spanning from their origin, trigger which segment is affected—to presentation, progression prognosis, few studies take into consideration variable sex. Notably, inherent disparities between female male biology warrants a more comprehensive representation within kidney. The omission sex fundamental carries substantial risk overlooking sex-specific mechanisms implicated health disease, along with potential differences responsiveness toxicity profiles sexes. This review emphasizes importance incorporating cellular, functional features activity models. For that, we thoroughly document propose strategic experimental framework to integrate sex-based human by outlining critical design criteria elucidate at cellular tissue levels. goal enhance accuracy unravel improve impact on efficacy safety profiles, paving way patient-specific treatment modalities.

Language: Английский

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Cell cycle visualization tools to study cardiomyocyte proliferation in real-time

Open Biology, Journal Year: 2024, Volume and Issue: 14(10)

Published: Oct. 1, 2024

Cardiomyocytes in the adult human heart are quiescent and those lost following injury not replaced by proliferating survivors. Considerable effort has been made to understand mechanisms underlying cardiomyocyte cell cycle exit re-entry, with view discovering therapeutics that could stimulate proliferation regeneration. The advent of large compound libraries robotic liquid handling platforms enabled screening thousands conditions a single experiment but success these screens depends on appropriateness quality model used. Quantification (human) high throughput remained problematic because conventional antibody-based staining is costly, technically challenging does discriminate between division failure karyokinesis or cytokinesis. Live imaging provided alternatives facilitate high-throughput have other limitations. Here, we (i) review features cardiomyocytes, (ii) discuss various fluorescent reporter systems, (iii) speculate what improve their predictive value context proliferation. Finally, consider how new methods can be used combination state-of-the-art three-dimensional cardiac organoid identify pro-proliferative signalling pathways regeneration heart.

Language: Английский

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Advancing Cardiac Organoid Engineering Through Application of Biophysical Forces

IEEE Reviews in Biomedical Engineering, Journal Year: 2024, Volume and Issue: 18, P. 211 - 230

Published: Dec. 9, 2024

Cardiac organoids represent an important bioengineering opportunity in the development of models to study human heart pathophysiology. By incorporating multiple cardiac cell types three-dimensional culture and developmentally-guided biochemical signaling, recapitulate numerous features tissue. However, tissue also experiences a variety mechanical forces as develops over course each contraction cycle. It is now clear that these impact cellular specification, phenotype, function, should be incorporated into engineering order generate better models. In this review, we discuss strategies for report effects organoid design on function cells. We then environment heart, including arising from elasticity, contraction, blood flow, stretch, efforts mimic biophysical cues organoids. Finally, review emerging areas research, development, formation multi-organ models, simulation spaceflight consider how investigations might benefit inclusion cues.

Language: Английский

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