From human joints to bioreactor setups: quantifying mechanical stimuli in cartilage physiology and regeneration

Bioreactors are widely used to apply mechanical stimuli to osteochondral (OC) explants and cartilage tissue-engineered (TE) constructs, yet their ability to replicate native joint mechanics is not well quantified. This study benchmarks common bioreactor loading protocols against a finite element (FE) model of the human knee during gait, enabling direct comparison to physiologically relevant mechanical parameters. A validated FE model of the human knee joint simulating the stance phase of gait was used to characterize physiological mechanical conditions, including maximum principal stress, maximum shear strain, pore pressure, and fluid velocity. These outputs were compared with those generated by representative bioreactor setups: dynamic unconfined compression (10-30%) and combined compression (10%) with ball rotation (±25°), which were applied to both OC plugs and TE constructs, and hydrostatic pressure (0.5-50 MPa), which was applied only to TE constructs. FE simulations evaluated spatial and magnitude-based agreement with native cartilage mechanics. In OC plugs, 10% unconfined compression generated maximum principal stresses (≈7.5 MPa) and pore pressures (≈4 MPa) closely matching native tissue (≈4.5 MPa and ≈5 MPa, respectively). In TE constructs, even at 30% unconfined strain, maximum principal stresses and pore pressures remained around 100 times lower than physiological values, while fluid velocities were 10 times higher. Hydrostatic loading of TE constructs at 5 MPa matched native pore pressures (≈5 MPa) but induced negligible strains. This study provides a quantitative framework for evaluating how well bioreactor loading regimens replicate physiological joint mechanics. The findings offer actionable guidance to experimentalists for selecting bioreactor conditions based on specific mechanical targets. This can lead to more effective design of in vitro cartilage studies and support translational strategies in cartilage repair and tissue engineering.