Strontium–calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration

Xiexing Wu; Ziniu Tang; Kang Wu; Yanjie Bai; Xiao Lin; Huilin Yang; Qiang Yang; Zheng Wang; Xinye Ni; Huiling Liu; Lei Yang

doi:10.1039/D1TB00439E

Strontium–calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration†

Xiexing Wu,

‡^a Ziniu Tang,‡^a Kang Wu,‡^a Yanjie Bai,^b Xiao Lin,^a Huilin Yang,^a Qiang Yang,^c Zheng Wang,^d Xinye Ni,*^e Huiling Liu*^f and Lei Yang

*^ag

Author affiliations

* Corresponding authors

^a Institute of Orthopedics and Department of Orthopedics, The First Affiliated Hospital, Soochow University, No. 708 Renmin Road, Suzhou 215006, P. R. China

^b School of Public Health, Medical College, Soochow University, Suzhou 215006, P. R. China

^c Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin 300211, P. R. China

^d Department of Orthopedics, PLA General Hospital, Beijing 100853, P. R. China

^e Second People's Hospital of Changzhou, Nanjing Medical University, No. 68 Gehu Road, Changzhou 213003, P. R. China
E-mail: nxy@njmu.edu.cn

^f Institute of Orthopedics, Medical College, Soochow University, Suzhou 215006, P. R. China
E-mail: liuhuilinghz@suda.edu.cn

^g Center for Health Science and Engineering (CHSE), School of Materials Science and Engineering, Hebei University of Technology, No. 8 Guangrong Road, Tianjin 300130, P. R. China
E-mail: ylei@hebut.edu.cn

Abstract

Vascularized bone tissue engineering is regarded as one of the optimal treatment options for large bone defects. The lack of angiogenic properties and unsatisfactory physicochemical performance restricts calcium phosphate cement (CPC) from application in vascularized bone tissue engineering. Our previous studies have developed a starch and BaSO₄ incorporated calcium phosphate hybrid cement (CPHC) with improved mechanical strength and handling properties. However, the bioactivity—especially the angiogenic ability—is still absent and requires further improvement. Herein, based on the reported CPHC and the osteogenic and angiogenic properties of strontium (Sr) ions, a strontium-enhanced calcium phosphate hybrid cement (Sr–CPHC) was developed to improve both biological and physicochemical properties of CPC. Compared to CPC, the initial setting time of Sr–CPHC was prolonged from 2.2 min to 20.7 min. The compressive strength of Sr–CPHC improved from 11.21 MPa to 45.52 MPa compared with CPC as well. Sr–CPHC was biocompatible and showed promotion of alkaline phosphatase (ALP) activity, calcium nodule formation and osteogenic relative gene expression, suggesting high osteogenic-inductivity. Sr–CPHC also facilitated the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and up-regulated the expression of the vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1). In vivo evaluation showed marked new bone formation in a rat calvarial defect model with Sr-CPHC implanted. Sr–CPHC also exhibited enhancement of neovascularization in subcutaneous connective tissue in a rat subcutaneous implantation model. Thus, the Sr–CPHC with the dual effects of osteogenesis and angiogenesis shows great potential for clinical applications such as the repair of ischemic osteonecrosis and critical-size bone defects.

Journal of Materials Chemistry B

Strontium–calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration†

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Strontium–calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration

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