Effects of Compression on Extracellular Matrix Synthesis by Chondrocytes and Chondrosarcoma Cells

Objective Mechanical loading is critical for chondrocyte function and cartilage matrix production, yet its effects on clustered chondrocytes in end-stage osteoarthritis and on chondrosarcoma cells remain poorly understood. This study investigated how cyclic compression influences chondrocytes and chondrosarcoma cells cultured either as single cells or as micromasses. Methods An organ-on-chip platform was used to apply cyclic compression to chondrocytes and chondrosarcoma cells embedded in agarose as single cells or micromasses mimicking chondrocyte clusters. Deformation during loading was assessed, and after four days of stimulation, gene and protein expression of cartilage markers and extracellular matrix components were analyzed. Results Chondrocyte micromasses deformed less than single cells and showed behavior resembling chondrosarcoma cells and their micromasses. All four culture models exhibited distinct mechanobiological responses after four days of compression. Mechanical loading promoted collagen I reorganization in micromasses and increased ACAN and COL2A1 expression, with enhanced matrix deposition aligned with the loading direction in one chondrocyte donor and one chondrosarcoma cell line. Semi-quantitative imaging suggested trends toward ECM deposition along the loading axis in some micromass conditions. Conclusion In this agarose-based organ-on-chip proof-of-concept model, cellular organization was associated with distinct responses to cyclic compression. These findings should be interpreted as model-specific observations from one OA donor and one chondrosarcoma cell line, and require validation in additional donors, cell lines, matrices, and loading conditions before broader conclusions can be drawn.