Kompendium 2020 Forschung & Klinik

TOP-Studien
44
3D Synovium-on-a-chip with scattering biosensing.
„Researchers were able to develop a
non-invasive lab-on-a-chip system for
the modelling of architectural changes
inside RA patient-derived synovial
organoids during inflammatory
remodeling. This constitutes as a
major technological advance as the
study presents the first translation
of human synovium organoids into
a miniaturized biochip format.“
Mario Rothbauer
in arthritic disease modelling. Currently his team is expanding this technological
platform for other musculoskeletal structures, including osteochondral,
adipose, and fibrous tissues. Essentially, patient-derived tissue microsystems
comprise microfluidic microchannels, isolated primary patient cells (i.e.,
fibroblast-like synoviocytes, chondrocytes, fibroblasts, or adipocytes), and
three-dimensional hydrogels as scaffolding material. In contrast to bioprinting,
where the basic shape is defined a priori by the printing technique, the microsystems
of the KCLOB form complex tissue-like structures resembling patient
joint tissues solely by the patient cells’ potential to remodel a bulk scaffold and
organize themselves into functional tissue-like structures.
Development of a Non-invasive Lab-on-a-chip System
Based on almost a decade of collaborative synovium-on-a-chip development,
basic researchers at the „Karl Chiari Lab for Orthopaedic Biology“
and the „Division of Rheumatology“ joined forces with Vienna University of
Technology, the University of Natural Resources and Life Sciences (BOKU),
and the TranslaTUM of Technical University of Munich, to develop a non-invasive
lab-on-a-chip system for the modelling of architectural changes inside
RA patient-derived synovial organoids during inflammatory remodeling. This
constitutes as a major technological advance as the study presents the first
translation of human synovium organoids into a miniaturized biochip format.
It demonstrated the formation of synovial organoids by in situ polymerization of
hydrogel with a high degree of position accuracy as well as a more reproducible
environment for organoid reorganization. Time-resolved light scattering
signals of 3D synovial organoids subjected to a TNF-α-mediated inflammatory
stimulus showed a significant scatter signal increase of 16% and
21% already at day 3 and 4, respectively. These alterations in light scattering
are a direct result of the structural and architectural changes within the
inflamed synovial organoid, featuring Cadherin-11-mediated thickening of
the synovial lining as well as the cellular network structures of the synovial
sublining with a strong Interleukin-6 and Interleukin-8 response.
Further Findings
The basic approach of combining multiple self-organizing biochip organoids
for crosstalk studies is currently under investigation for molecular RA and OA
research. While microfluidic models recapitulating molecular aspects of bone