Bone regeneration is a highly synchronized process that requires multiple
biochemical, bioelectrical, mechanical, and other physiological cues. The restoration
Journal Pre-proof
2
and delivery of electrical cues locally through piezoelectric materials have been
demonstrated to facilitate osteogenesis in vitro and bone repair in vivo. However, the
underlying mechanism by which piezoelectric stimulation promotes osteogenesis and
bone repair remains unclear yet, limiting the design and clinical application of
piezoelectric materials for bone repair. Herein, a piezoelectric BaTiO3/Ti6Al4V
(BT/Ti) scaffold was prepared by hydrothermal synthesis of a uniform BaTiO3 layer
on three dimensionally printed Ti6Al... More
Bone regeneration is a highly synchronized process that requires multiple
biochemical, bioelectrical, mechanical, and other physiological cues. The restoration
Journal Pre-proof
2
and delivery of electrical cues locally through piezoelectric materials have been
demonstrated to facilitate osteogenesis in vitro and bone repair in vivo. However, the
underlying mechanism by which piezoelectric stimulation promotes osteogenesis and
bone repair remains unclear yet, limiting the design and clinical application of
piezoelectric materials for bone repair. Herein, a piezoelectric BaTiO3/Ti6Al4V
(BT/Ti) scaffold was prepared by hydrothermal synthesis of a uniform BaTiO3 layer
on three dimensionally printed Ti6Al4V scaffold. The BT/Ti scaffolds exhibited
piezoelectricity and favorable biocompatibility with RAW264.7 macrophages after
polarization. In vitro results demonstrated that the piezoelectric effects of the poled
BT/Ti scaffolds promoted M2 polarization of macrophages and immunoregulatory
osteogenesis of MC-3T3 osteoblasts. In a subcutaneous implantation model, a higher
proportion of CD68+ CD206+ M2 macrophages was observed in the tissues around the
poled BT/Ti scaffolds under low intensity pulsed ultrasound (LIPUS) stimulation.
Improvements in macrophage M2 polarization and bone regeneration were further
identified in a sheep cervical corpectomy model. RNA sequencing and mechanistic
investigation revealed that the piezoelectric BT/Ti (poled) scaffolds inhibited the
inflammatory MAPK/JNK signaling cascade and activated oxidative phosphorylation
(OXPHOS) and ATP synthesis in macrophages. Collectively, our study provides a
promising method for regulating the immune microenvironment and enhancing bone
regeneration using polarized piezoelectric BT/Ti scaffolds.
