Articular cartilage experiences compressive and shear stresses, which, under excessive loading or trauma, can lead to chondral lesions. Its repair ability is limited by the absence of blood vessels, lymphatic vessels and nerves. While conventional treatments yield temporary results with fibrocartilaginous tissue, tissue engineering and mechanical stimulation offer promising alternatives by addressing the role of extracellular forces. This study investigates whether GelMA is an appropriate scaffold to mechanically activate endogenous TGF-β and promote hBMSCs chondrogenesis. Cylindrical 15% (w/v) GelMA scaffolds with 0.1% (w/v) Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) (200 mm 3 ) were UV-cured. For the cell-free experiment, latent TGFβ-1 (100 ng/mL) was added into DMEM high glucose containing 1.25 mg/mL BSA. The scaffolds were either exposed to mechanical loading in an in-house bioreactor, with 10% or 20% dynamic compression (DC) strain and 1 Hz shear applied or maintained under free swelling (FS) conditions for 6 hours. In the cell experiment, 5 million hBMSCs (from two donors, with ethical approval) were encapsulated in the scaffold and either mechanically stimulated for 1 hour per day, 5 days a week, over two weeks culture, or subjected to FS in chondro-permissive medium (w/o TGFβ-1). Samples were then analysed using gene expression and TGFβ- ELISA. 10% and 20% DC activated latent TGFβ-1 at higher extent compared to FS condition in GelMA scaffolds, similar to results obtained in our group's previous studies using PU scaffolds (Figure 1 A). On day 14 (Figure 1 B), both 10% and 20% DC showed enhanced endogenous TGF-β1 activation compared to FS. For gene expression (Figure 1 C), col2a1 exhibited an upregulation in the loaded groups compared to the FS, although this difference did not reach statistical significance. In addition, col10a1 expression was significantly higher in the 10% DC group compared to the 20% DC and FS groups, indicating that the hBMSCs might be adopting a more hypertrophic phenotype. This study demonstrates that DC strain and shear activate TGF-β and induce chondrogenesis in hBMSCs encapsulated in GelMA, in the absence of TGF-β supplementation. Further donors will be added to reinforce these findings. For any figures or tables, please contact the authors directly.
Cordeiro et al. (Mon,) studied this question.