Emulating the chondrocyte microenvironment using multi-directional mechanical stimulation in a cartilage-on-chip

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Mechanobiology

Background:

• Articular cartilage chondrocytes respond to mechanical stimuli via pericellular matrix.
• Understanding chondrocyte response to mechanical cues is crucial for cartilage repair and regeneration.

Purpose of the Study:

• To investigate the impact of different mechanical stimulation types on chondrocyte phenotype and extracellular matrix (ECM) production.
• To utilize a cartilage-on-chip system for controlled mechanical stimulation of chondrocytes.

Main Methods:

• A cartilage-on-chip system was developed to apply compressive and multi-directional mechanical stimulation to 3D chondrocyte-laden agarose hydrogels.
• Chondrocyte gene expression (COL2A1, COL1A1), inflammatory cytokine production (IL-6, IL-1β, TNF-α), and glycosaminoglycan (GAG) production were analyzed.

Main Results:

• Mechanical stimulation initially increased IL-6 production but minimally affected IL-1β and TNF-α.
• Enhanced expression of COL2A1 (hyaline cartilage marker) and decreased COL1A1 (fibrotic marker) were observed, with multi-directional stimulation showing a greater effect.
• Significant increase in GAG production and deposition of pericellular and interstitial matrices, mimicking in vivo conditions, were noted, particularly with multi-directional stimulation.

Conclusions:

• Mechanical cues are critical for emulating the in vitro chondrocyte microenvironment.
• Multi-directional mechanical stimulation is more effective in promoting hyaline cartilage matrix production compared to other tested stimuli.
• The cartilage-on-chip system provides a valuable platform for studying chondrocyte mechanobiology and developing cartilage regeneration strategies.