Stimuli-responsive gyroid Scaffolds: hierarchical architecture and electric stimulation promote bone regeneration

Osteoporotic fractures in older adults place a significant burden on healthcare systems due to prolonged healing times and escalating costs. Innovative approaches closely mimicking the human bone microenvironment are paramount for advancing bone tissue regeneration. This study leverages a sacrificial template methodology to develop hierarchical 3D porous gelatin-NaNbO₃@PDMS scaffolds with gyroid structures mimicking cancellous bone architecture, tailored for enhanced stimuli-responsive biological performance. Modulating porosity levels (∼0%, 18 %, and 63 %) enables macro-to-micro pore transitions, highlighting how porosity and zero-curvature surfaces impact critical properties for bioactive scaffold applications. Under simulated physical activity pressures, lower scaffold porosity enhances structural integrity, mechanical stability, and damping capacity, driven by reduced thickness plastic deformation. Corona discharge poling generates electrically charged stimuli-responsive scaffolds, enhancing electric field intensity through charge trapping. Combined with ultrasound stimulation (50 and 250 mW·cm⁻²), it boosts metabolic activity, gene expression, and mineralization, increasing calcium deposition by up to 1200 % compared to unstimulated controls. Finite element analysis reveals that the 63 % porosity scaffolds generate a sixfold stronger electric field than its 18 % counterpart, enhancing stimuli-responsive cell alignment, with ultrasound stimulation boosting it by ∼10 %. These discoveries in zero-curvature geometries and stimuli-responsive systems redefine bone regeneration strategies by mimicking bone anisotropy through electric field stimulation, offering transformative insights for advanced biomaterials in implants and physiotherapy.