Calcium phosphate-based materials regulate osteoclast-mediated osseointegration

Xiaogang Wang; Yuanman Yu; Luli Ji; Zhen Geng; Jing Wang; Changsheng Liu

doi:10.1016/j.bioactmat.2021.05.003

Calcium phosphate-based materials regulate osteoclast-mediated osseointegration

Bioact Mater. 2021 May 12;6(12):4517-4530. doi: 10.1016/j.bioactmat.2021.05.003. eCollection 2021 Dec.

Authors

Xiaogang Wang^{1

2}, Yuanman Yu^{1

2}, Luli Ji^{1

2}, Zhen Geng^{1

2}, Jing Wang^{1

3}, Changsheng Liu^{1

2

4}

Affiliations

¹ Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China.
² Engineering Research Center for Biomedical Materials of the Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China.
³ The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
⁴ Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, 200237, PR China.

Abstract

Calcium phosphate-based materials (CaP) have been widely used as bone graft substitutes with a decent osseointegration. However, the mechanism whereby cells function and repair the bone defect in CaP micro-environment is still elusive. The aim of this study is to find the mechanism how osteoclast behaviors mediate bone healing with CaP scaffolds. Recent reports show that behaviors of osteoclast are closely related with osteogenesis, thus we make a hypothesis that active osteoclast behaviors induced by CaP facilitate bone healing. Here, we found a new mechanism that CaP can regulate osteoclast-mediated osseointegration. Calcium phosphate cement (CPC) is selected as a representative CaP. We demonstrate that the osteoclast-mediated osseointegration can be strongly modulated by the stimulation with CaP. An appropriate Ca/P ratio in CaP can effectively promote the RANKL-RANK binding and evoke more activated NF-κB signaling transduction, which results in vigorous osteoclast differentiation. We observe significant improvement of bone healing in vivo, owing to the active coupling effect of osteoclasts. What is more noteworthy is that the phosphate ions released from CaP can be a pivotal role regulating osteoclast activity by changing Ca/P ratio readily in materials. These studies suggest the potential of harnessing osteoclast-mediated osteogenesis in order to develop a materials-manipulated approach for improving osseointegration.

Keywords: Bone regeneration; Calcium phosphate-based materials; Osseointegration; Osteoclast.