Enhancing osteoinduction and bone regeneration of biphasic calcium phosphate scaffold thought modulating the balance between pro-osteogenesis and anti-osteoclastogenesis by zinc doping

Biphasic calcium phosphate (BCP) is a promising bone regeneration material with an adjustable degradation rate, and ions doping is an effective method to improve its bone repair effect. However, few studies have focused on the role of ions doping-mediated osteogenesis and osteoclastogenesis balance in bone regeneration. In order to improve the bone repair effect of BCP and emphasize the role of osteogenesis and osteoclastogenesis balance regulated by ions doping to promote bone regeneration. Here, zinc (Zn), an essential trace element with pro-osteogenesis and anti-osteoclastogenesis, was dopped into BCP scaffolds, and its effects on the physicochemical properties, in vitro cytological responses, in vivo osteoinduction, and bone defect regeneration of BCP were systematically investigated. Results showed that Zn was successfully introduced into the crystal lattice of BCP. The differentiation of both osteoblasts and osteoclasts showed a doping content-dependent behavior. By increasing the doping content (0–5 mol.%), the anti-osteoclastogenesis effect of BCP gradually increased, while its pro-osteogenesis performance first increased and then decreased. ThoughBCP with a doping content of 5 mol.% could promote osteogenic differentiation of stem cells and reduced fibrous capsule encapsulation, it could not enhance ectopic bone formation or bone regeneration due to its excessive anti-osteoclastogenesis. BCP with a doping content of 2.5 mol.% remarkably enhanced the osteoinduction activity and accelerated new bone formation, which were associated with its highest pro-osteogenesis and appropriate anti-osteoclastogenesis activity. This study highlights on regulating the balance between pro-osteogenesis and anti-osteoclastogenesis by Zn doping and paves the way for the development of a more osteoinductive calcium phosphate-based material for bone regeneration.