Strontium modulates osteogenic activity of bone cement composed of bioactive borosilicate glass particles by activating Wnt/β-catenin signaling pathway

Xu Cui; Yadong Zhang; Jianyun Wang; Chengcheng Huang; Yudong Wang; Hongsheng Yang; Wenlong Liu; Ting Wang; Deping Wang; Guocheng Wang; Changshun Ruan; Dafu Chen; William W Lu; Wenhai Huang; Mohamed N Rahaman; Haobo Pan

doi:10.1016/j.bioactmat.2020.02.016

Strontium modulates osteogenic activity of bone cement composed of bioactive borosilicate glass particles by activating Wnt/β-catenin signaling pathway

Bioact Mater. 2020 Mar 14;5(2):334-347. doi: 10.1016/j.bioactmat.2020.02.016. eCollection 2020 Jun.

Authors

Xu Cui^{1

2}, Yadong Zhang^{3

4}, Jianyun Wang⁵, Chengcheng Huang¹, Yudong Wang¹, Hongsheng Yang¹, Wenlong Liu¹, Ting Wang⁶, Deping Wang², Guocheng Wang¹, Changshun Ruan¹, Dafu Chen⁷, William W Lu^{1

8}, Wenhai Huang², Mohamed N Rahaman⁹, Haobo Pan¹

Affiliations

¹ Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, PR China.
² Schools of Materials Science and Engineering, Tongji University, Shanghai, 201804, PR China.
³ Department of Orthopaedics, Shanghai Fengxian Central Hospital, South Campus of the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, 201499, PR China.
⁴ Department of Orthopaedics, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, 201499, PR China.
⁵ Shenzhen Healthemes Biotechnology Co.Ltd, Shenzhen, 518102, PR China.
⁶ Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, Department of Orthopaedics, The University of Hong Kong-Shenzhen Hospital, University of Hong Kong, Shenzhen, 518053, PR China.
⁷ Laboratory of Bone Tissue Engineering Beijing, Laboratory of Biomedical Materials, Beijing Research Institute of Orthopaedics and Traumatology, Beijing Jishuitan Hospital, Beijing, 100035, PR China.
⁸ Department of Orthopaedics and Traumatology, The University of Hong Kong, Room 907, Lab Block, 21 Sassoon Road, Hong Kong SAR, PR China.
⁹ Department of Materials Science and Engineering, Missouri University of Science and Technology, MO, 65409-0340, USA.

Abstract

There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery. Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capacity in vivo. However, the amount of Sr in the cement to provide an optimal combination of physicochemical properties and capacity to stimulate bone regeneration and the underlying molecular mechanism of this stimulation is yet to be determined. In this study, bone cements composed of bioactive borosilicate glass particles substituted with varying amounts of Sr (0 mol% to 12 mol% SrO) were created and evaluated in vitro and in vivo. The setting time of the cement increased with Sr substitution of the glass. Upon immersion in PBS, the cement degraded and converted more slowly to HA (hydroxyapatite) with increasing Sr substitution. The released Sr²⁺ modulated the proliferation, differentiation, and mineralization of hBMSCs (human bone marrow mesenchymal stem cells) in vitro. Osteogenic characteristics were optimally enhanced with cement (designated BG6Sr) composed of particles substituted with 6mol% SrO. When implanted in rabbit femoral condyle defects, BG6Sr cement supported better peri-implant bone formation and bone-implant contact, comparing to cements substituted with 0mol% or 9mol% SrO. The underlying mechanism is involved in the activation of Wnt/β-catenin signaling pathway in osteogenic differentiation of hBMSCs. These results indicate that BG6Sr cement has a promising combination of physicochemical properties and biological performance for minimally invasive healing of bone defects.

Keywords: Bioactive borosilicate glass; Bone regeneration; Injectable bone cement; Signaling pathway; Strontium.