Copper-Doped Barium Titanate Coating: A Piezoelectric Match to Natural Bone for Enhanced Osteogenesis

Barium titanate (BaTiO₃) is a conventional piezoelectric material, but its biocompatibility is limited. Besides, its piezoelectric property is significantly different from that of natural bone tissue. To address this, we have developed an innovative coating material that mimics the piezoelectric characteristics of natural bone with a <i>d</i>₃₃ coefficient of 7.8 pm/V. The material was fabricated by replacing titanium (Ti) in the BaTiO₃ crystal lattice with copper (Cu), a strategy that not only augments the piezoelectric response but also harnesses the osteogenic potential of Cu. BaCu_<i>x</i>Ti_1-<i>x</i>O₃ reveals an enhanced piezoelectric performance and actively promotes the adhesion, proliferation, and differentiation of MC3T3-E1 cells. Moreover, doped Cu modulates osteogenic differentiation through the upregulation of the Wnt4/β-catenin/SP7/Osterix signaling pathway. The synergistical effect caused by piezoelectricity and the biological activity of Cu contributed to promoting bone regeneration in vivo; in particular, H-BaCu_<i>x</i>Ti_1-<i>x</i>O₃ led to a 15.6% increase of the bone volume percentage compared to BaTiO₃. Furthermore, H-BaCu_<i>x</i>Ti_1-<i>x</i>O₃ promoted the accumulation of bone extracellular matrix components including Osteopontin (OPN) and Collagen Type I (COL-1), which, respectively, increased by 62.12 and 155%. The synergistic interplay between the piezoelectric property of BaCu_<i>x</i>Ti_1-<i>x</i>O₃ and the osteogenic influence of Cu has significantly improved the repairing process of bone defects, offering a promising advancement in the field of orthopedic implant coatings.