Multi-objective design and validation of a bioinspired tri-zonal scaffold for tendon-bone interfaces

The tendon-bone interface exhibits a complex gradient in mechanical and morphological properties, enabling robust load transfer between soft and hard tissues. Replicating this functionality in engineered scaffolds remains challenging. Here, we present a computational-experimental framework for developing tri-zonal scaffolds with spatially varying stiffness and zone-specific architectures for tendon-bone interface applications. A hybrid lattice combining strut-based and surface-based geometries was used to generate tendon-like, transitional, and bone-like zones. Homogenization-based modeling and 3D finite element simulations were used to screen 36 feasible design configurations. Two representative designs were fabricated via fused deposition modeling and integrated with an alginate-gelatin hydrogel. Micro-computed tomography was used to assess manufacturing fidelity, and identify architecture-dependent geometric deviations, while mechanical testing characterized the response of the fabricated scaffolds and hydrogel-integrated constructs. Design A exhibited a 72–93% higher maximum tensile force than Design B, with failure observed predominantly within the hydrogel adjacent to the scaffold-hydrogel interface. Preliminary in vitro observations with MC3T3-E1 preosteoblasts showed qualitative differences in cell morphology and spatial organization between scaffold architectures and zones. These findings demonstrate the use of a multi-objective design framework for integrating zone-specific mechanical and morphological requirements and provide a basis for further development of engineered soft-hard tissue interfaces.