Predicting Cell Differentiation in Mechanically Stimulated Biphasic Osteochondral Scaffolds Using Fluid-Structure Interaction Modelling.

Osteochondral defects, involving both articular cartilage and subchondral bone, can lead to joint degeneration and osteoarthritis. Recent advances in 3D-printed biphasic scaffolds offer promising opportunities to recreate physiological microenvironments for tissue regeneration. In tissue engineering, these scaffolds can be mechanically stimulated to promote targeted cartilage and bone formation. While computational models have been widely used to study mechanically induced cellular responses in monophasic scaffolds, time-dependent modelling of biphasic osteochondral systems remains relatively scarce. In this study, a fluid-structure interaction (FSI) framework coupled with a mechanoregulatory algorithm was developed to predict mechanically induced early-stage mesenchymal stem cell (MSC) differentiation in biphasic open-porous osteochondral scaffolds comprising chondral and bone layers designed for direct ink writing (DIW). In a second model, an interfacial barrier layer representing the native osteochondral interface was integrated. Dynamic compressive loading (1 Hz, 2.5% strain) was applied. The simulations predicted region-specific differentiation patterns in both the chondral and subchondral bone regions. In the scaffold without a barrier layer, approximately 68.9% of MSCs in the chondral layer and 93.4% of MSCs in the bone layer underwent chondrogenic and osteogenic differentiation, respectively. Incorporation of the barrier layer caused only minor changes, reducing predicted cartilage and bone differentiation by approximately 1.5% and 3.9%, respectively. Overall, this study highlights the capability of computational modelling to predict mechanobiological responses in complex osteochondral systems and support scaffold design and effective mechanical stimulation protocols.