Immune cell infiltration to synovium in joint on a chip

A beautiful paper from Moretti/Lopa group integrating cartilage-on-a-chip and synovium-on-a-chip to present a unique joint-on-a-chip model. This model recapitulated monocyte extravasation into the synovium of patients with osteoarthritis. The system was composed of synovial compartment included a perfusable endothelialized channel for monocyte injection, a chondral compartments, and a channel for synovial fluid injection.

Results

 The proposed system incorporated patient-derived synovial fibroblasts, articular chondrocytes, and a continuous endothelial monolayer. The authors assessed the extravasation of monocytes in response to chemokines and osteoarthritis synovial fluid. They observed that, in chips with endothelial cells, higher number of monocytes extravasated in response to the chemokine mix and osteoarthritis synovial fluid. This model proved the role of osteoarthritis synovial fluid in inducing monocytes to extravasate to the synovial compartment.

DigesTable of the paper Mondadori, C., et al., Recapitulating monocyte extravasation to the synovium in an organotypic microfluidic model of the articular joint. Biofabrication, 2021. 13(4): p. 045001. This paper is reproduced under https://creativecommons.org/licenses/by/4.0/. The image of the chip was edited for better clarity, data in the table and text were compiled and interpreted by AZAR Innovations.

Method

The chip included three gel compartments and two microfluidic channels. The authors used primary human umbilical vein endothelial cells, patient-derived synovial fibroblasts, synovial fluid, articular chondrocytes, and human primary monocytes which were isolated from blood.
Fabrication: soft lithography with PDMS
Sterilization:
Cell incorporation: synovial fibroblasts and articular chondrocytes embedded in fibrin gel were injected into gel compartments, endothelial cells and monocytes were injected to endothelial channel sequentially
Perfusion/refreshing: syringe pump
Treatment: chemokine mix
On-chip read-outs: live-dead staining, end-point microscopy
Off-chip read-outs: Off-chip imaging, immuno-histo chemistry

Strong points:

+ 5 side by side microchannels separated by trapezoidal posts
+ Co-culture of many relevant cell types
+ Relevant environmental stimuli

Nothing is perfect! The system can also improve:

– They only have flow for the formation of endothelium, the monocyte extravasation occurs in a static condition of the endothelial channel which is not physiological

Conclusion and outlook

This joint-on-a-chip model mimicked monocyte extravasation to synovium. The model incorporates both synovium and cartilage cells and can be used to investigate the effect of extravasated monocytes on synovium and cartilage cells.