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. Using a finite element (FE) modeling approach, this study benchmarks common bioreactor loading protocols against 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 key mechanical variables: maximum principal stress, maximum shear strain, pore pressure, and fluid velocity. These outputs were compared with FE analyses of representative bioreactor setups: dynamic unconfined compression (UC) (10%-30%) and combined compression (10%) with ball rotation (±25°), applied to both OC plugs and TE constructs, and hydrostatic pressure (0.5-50 MPa), applied only to TE constructs. In OC plugs, 10% UC 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% UC, 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 establishes a quantitative framework for evaluating how well bioreactor loading regimens replicate physiological joint mechanics. While limited to a single-subject dataset, this framework provides a robust in silico benchmarking methodology and identifies comparative indicators for evaluating bioreactor setups against specific mechanical variables. This work lays the foundation for a more standardized design of in vitro cartilage studies, supporting targeted translational strategies in cartilage repair and tissue engineering.