Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing

Rothbauer, Mario; Höll, Gregor; Eilenberger, Christoph; Kratz, Sebastian Rudi Adam; Farooq, Bilal; Schuller, Patrick; Calvo, Isabel Olmos; Byrne, Ruth A.; Meyer, Brigitte; Niederreiter, Birgit; Küpcü, Seta; Sevelda, Florian; Holinka, Johannes; Hayden, Oliver; Tedde, Sandro F.; Kiener, Hans P.; Ertl, Peter

doi:10.1039/c9lc01097a

Cited by 43 publications

(48 citation statements)

References 49 publications

(57 reference statements)

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“…A final study to be outlined in this review was conducted by Rothbauer et al that used a light scattering platform for synovial organoid development and analysis [ 153 ]. The light scattering station consisted of multiplexed 488 nm sapphire laser, split by beam splitters, collimators, and fiber couplers.…”

Section: Application Of Ooc Devices With Integrated Sensorsmentioning

confidence: 99%

“… Investigation of tissue-level remodeling in regard to inflammatory arthritis, reproduced from open access article Ref. [ 153 ]. Graphic showing setup of the chip with integrated biosensors, consisting of four separate microchambers that hold human synovium organoids.…”

Section: Figurementioning

confidence: 99%

“…Investigation of tissue-level remodeling in regard to inflammatory arthritis, reproduced from open access article Ref [153]…”

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confidence: 99%

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Advancement of Sensor Integrated Organ-on-Chip Devices

Clarke

Hartse

Asli

et al. 2021

Sensors

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Organ-on-chip devices have provided the pharmaceutical and tissue engineering worlds much hope since they arrived and began to grow in sophistication. However, limitations for their applicability were soon realized as they lacked real-time monitoring and sensing capabilities. The users of these devices relied solely on endpoint analysis for the results of their tests, which created a chasm in the understanding of life between the lab the natural world. However, this gap is being bridged with sensors that are integrated into organ-on-chip devices. This review goes in-depth on different sensing methods, giving examples for various research on mechanical, electrical resistance, and bead-based sensors, and the prospects of each. Furthermore, the review covers works conducted that use specific sensors for oxygen, and various metabolites to characterize cellular behavior and response in real-time. Together, the outline of these works gives a thorough analysis of the design methodology and sophistication of the current sensor integrated organ-on-chips.

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Section: Application Of Ooc Devices With Integrated Sensorsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Advancement of Sensor Integrated Organ-on-Chip Devices

Clarke

Hartse

Asli

et al. 2021

Sensors

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“…Overall, these results suggest that the purity of FLS populations is improving organoid formation reproducibility due to immune cell depletion. Since on-chip cultivation of artificial tissues is known for accumulation and retention of secreted molecules 33,34 , secretion analysis from collected supernatants of the above organoid cultures were conducted to monitor secretory behaviour for FLS of increasing passages. Results from our comparative secretion analysis of IL-6, IL-8, MMP-13 and VEGF up to passage p5 are shown in Fig.…”

Section: Impact Of Passaging On the Formation Of Chip-based Synovial Organoidsmentioning

confidence: 99%

“…molecule secretion. 22 More recently, also microphysiological models and organ-on-a-chip devices have been introduced to model various aspects of arthritic diseases: Ma et al established a co-culture of human FLS (synovial sarcoma SW982 cell line) with murine pre-osteoclasts (RAW264.7) and bone-marrow-derived stem cells (BMSCs) to study FLS migration and invasion-mediated bone erosion in RA. 23 Nonetheless, to date most systems rely on non-human and/or immortalised cell lines with no microsystem using primary human cell types to establish these complex 3D co-cultures to model arthritic diseases.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a human three-dimensional chip-based chondro-synovial co-culture joint model for reciprocal cross-talk studies in arthritis research

Rothbauer

Byrne

Schobesberger

et al. 2021

Preprint

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Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane, which is the joint capsule's inner layer, is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, the synovial-chondral axis in rheumatoid arthritis has yet not been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue co-culture model that simulates the reciprocal cross-talk between individual synovial and chondral organoids. We now demonstrate that chondral organoids, when co-cultivated with synovial organoids, induce a higher degree of physiological cartilage architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross-talk in the modelling of arthritic diseases.

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Global Literature Analysis of Organoid and Organ‐on‐Chip Research

Shoji

Davis

Mummery

et al. 2023

Adv Healthcare Materials

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Organoids and cells in organ‐on‐chip platforms replicate higher‐level anatomical, physiological, or pathological states of tissues and organs. These technologies are widely regarded by academia, the pharmacological industry and regulators as key biomedical developments. To map advances in this emerging field, a meta‐analysis based on a quality‐controlled text‐mining algorithm is performed. The analysis covers titles, keywords, and abstracts of categorized academic publications in the literature and preprint databases published after 2010. The algorithm identifies and tracks 149 and 107 organs or organ substructures modeled as organoids and organ‐on‐chip, respectively, stem cell sources, as well as 130 diseases, and 16 groups of organisms other than human and mouse in which organoid/organ‐on‐chip technology is applied. The meta‐analysis illustrates changing diversity and focus in organoid/organ‐on‐chip research and captures its geographical distribution. The downloadable dataset provided is a robust framework for researchers to interrogate with their own questions.

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Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing

Abstract: We demonstrate that the integration of complex human synovial organ cultures in a lab-on-a-chip provides reproducible and reliable information on how systemic stress factors affect synovial tissue architectures using light scatter biosensing.

Cited by 43 publications

References 49 publications

Advancement of Sensor Integrated Organ-on-Chip Devices

Advancement of Sensor Integrated Organ-on-Chip Devices

Establishment of a human three-dimensional chip-based chondro-synovial co-culture joint model for reciprocal cross-talk studies in arthritis research

Global Literature Analysis of Organoid and Organ‐on‐Chip Research

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