Functional designs of hybrid scaffolds for bone substitute − biomechanics and biocompatibility

• Sandwich-type scaffolds integrating TPMS architectures were designed and additively manufactured. • Manufacturability, mechanical behavior, permeability, and biocompatibility were systematically evaluated. • Results of mechanical tests and permeability of the scaffolds are desirable for the functional requirements of skeletal structures. • In vitro assessments demonstrated favorable cellular adhesion, proliferation, and overall biocompatibility. Triply periodic minimal surface (TPMS) structures provide porous, interconnected geometries with bone-like stiffness and permeability, yet hybrid TPMS designs remain underexplored. This study develops three 3D-printed hybrid TPMS scaffolds for mandibular segmental defect reconstruction, targeting manufacturable bone analogs with optimized mechanics and pore architectures. Scaffolds were assessed for printing fidelity, mechanical behavior, fluid transport, and in vitro biocompatibility. All designs exhibited high geometric accuracy relative to their digital models. Compression tests showed elastic moduli of 3.36–3.91 GPa and yield strengths of 88.20–128.52 MPa, meeting requirements for mandibular reconstruction. Finite element simulations confirmed that the R1-type scaffold sustained complex physiological loading, with predictive accuracies of 87% for mechanical response and 53% for permeability. Flow tests further demonstrated permeabilities within the range of cancellous bone. In vitro analyses indicated that surface activation enhanced cell adhesion and proliferation, while VEGF-loaded cryogels promoted angiogenic activity. These findings highlight the potential of functionally graded-scaffold design can optimize stress distribution and nutrient transport, thereby offering a strategy for future surgical reconstruction of critical-sized bony defects.