This study presents a pioneering biomimetic scaffold that combines piezoelectric and topographical enhancement with the osteogenic abilities of hydroxyapatite (HAp). The scaffold is designed to mimic the native bone tissue microenvironment, which is crucial for effective bone regeneration. The HAp is incorporated into polyvinylidene fluoride-co-trifluoroethylene (P(VDF-TrFE)) in a freestanding form, leveraging its natural osteogenic potential within a piezoelectric framework. Comprehensive in vitro and in vivo investigations demonstrate the scaffold's potential to accelerate bone regeneration through three key mechanisms: electrical, topographical, and paracrine. The electrical origin enhances cell proliferation and osteogenic differentiation by generating an electric field, the topographical origin improves cell adhesion and morphology by mimicking the intricate extracellular matrix, and the paracrine origin modulates growth factor expression to promote bone healing. The findings provide a foundation for future advancements in biomaterial design for bone regeneration and regenerative medicine applications.This study presents a pioneering biomimetic scaffold that combines piezoelectric and topographical enhancement with the osteogenic abilities of hydroxyapatite (HAp). The scaffold is designed to mimic the native bone tissue microenvironment, which is crucial for effective bone regeneration. The HAp is incorporated into polyvinylidene fluoride-co-trifluoroethylene (P(VDF-TrFE)) in a freestanding form, leveraging its natural osteogenic potential within a piezoelectric framework. Comprehensive in vitro and in vivo investigations demonstrate the scaffold's potential to accelerate bone regeneration through three key mechanisms: electrical, topographical, and paracrine. The electrical origin enhances cell proliferation and osteogenic differentiation by generating an electric field, the topographical origin improves cell adhesion and morphology by mimicking the intricate extracellular matrix, and the paracrine origin modulates growth factor expression to promote bone healing. The findings provide a foundation for future advancements in biomaterial design for bone regeneration and regenerative medicine applications.