Int J Biol Sci 2019; 15(6):1113-1124. doi:10.7150/ijbs.32358 This issue

Research Paper

Hypoxia-Mimicking Cobalt-Doped Borosilicate Bioactive Glass Scaffolds with Enhanced Angiogenic and Osteogenic Capacity for Bone Regeneration

Zhengwei Deng1,2*, Bocai Lin3*, Zenghui Jiang4*, Wenhai Huang5, Jiusheng Li3, Xiangqiong Zeng3, Hui Wang3✉, Deping Wang5✉, Yadong Zhang1,6✉

1. Department of Orthopedics, South Campus of Shanghai Sixth People's Hospital Affiliated of Shanghai University of Medicine&Health Sciences, 279 zhouzhu road, Shanghai 220120, People's Republic of China.
2. Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.
3. Laboratory for Advance Lubricating Materials, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, People's Republic of China.
4. Department of Orthopedic Surgery, Zhejiang Hospital, Hangzhou 310013, People's Republic of China.
5. School of Materials Science and Engineering, Tongji University, Shanghai 200092, People's Republic of China.
6. Shanghai Fengxian District Central Hospital Affiliated of Southern Medical University, Shanghai 201400, People's Republic of China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Deng Z, Lin B, Jiang Z, Huang W, Li J, Zeng X, Wang H, Wang D, Zhang Y. Hypoxia-Mimicking Cobalt-Doped Borosilicate Bioactive Glass Scaffolds with Enhanced Angiogenic and Osteogenic Capacity for Bone Regeneration. Int J Biol Sci 2019; 15(6):1113-1124. doi:10.7150/ijbs.32358. Available from

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Graphic abstract

The osteogenic capacity of synthetic bone substitutes is will be highly stimulated by a well-established functional vascularized network. Cobalt (Co) ions are known that can generate a hypoxia-like response and stimulates the production of kinds of angiogenic factors. Herein, we investigated the mechanism of cobalt-doped bioactive borosilicate (36B2O3, 22CaO, 18SiO2, 8MgO, 8K2O, 6Na2O, 2P2O5; mol%) glass scaffolds for bone tissues repairing and blood vessel formation in the critical-sized cranial defect site of rats and their effects on the hBMSCs in vitro were researched. The scaffolds can control release Co2+ ions and convert into hydroxyapatite soaking in simulative body fluids (SBF). The fabircated scaffolds without cytotoxic strongly improves HIF-1α generation, VEGF protein secretion, ALP activity and upregulates the expression of osteoblast and angiogenic relative genes in hBMSCs. Eight weeks after implantation, the bioactive glass scaffolds with 3wt % CoO remarkablely enhance bone regeneration and blood vascularized network at the defective site. In conclusion, as a graft material for bone defects, low-oxygen simulated cobalt-doped bioactive glass scaffold is promising.

Keywords: bioactive glass scaffolds, cobalt ions, hypoxia-like response, bone regeneration, blood vascularized network