Theranostics 2020; 10(6):2759-2772. doi:10.7150/thno.42006

Research Paper

A biocompatible vascularized graphene oxide (GO)-collagen chamber with osteoinductive and anti-fibrosis effects promotes bone regeneration in vivo

Huimin Fang1,2*, Chao Luo1,2*, Shaokai Liu1,2, Muran Zhou1,2, Yuyang Zeng1,2, Jinfei Hou1,2, Lifeng Chen1,2, Shan Mou1,2, Jiaming Sun1,2✉, Zhenxing Wang1,2✉

1. Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
2. Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan 430022, China
*These authors contributed equally to this work.

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Fang H, Luo C, Liu S, Zhou M, Zeng Y, Hou J, Chen L, Mou S, Sun J, Wang Z. A biocompatible vascularized graphene oxide (GO)-collagen chamber with osteoinductive and anti-fibrosis effects promotes bone regeneration in vivo. Theranostics 2020; 10(6):2759-2772. doi:10.7150/thno.42006. Available from

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The survival of transplanted cells and tissues in bone regeneration requires a microenvironment with a vibrant vascular network. A tissue engineering chamber can provide this in vivo. However, the commonly used silicone chamber is biologically inert and can cause rejection reactions and fibrous capsule. Studies have revealed that collagen is highly biocompatible and graphene oxide (GO) could regulate osteogenic activity in vivo. Besides, GO can be cross-linked with natural biodegradable polymers to construct scaffolds.

Methods: A vascularized GO-collagen chamber model was built by placing vessels traversing through the embedded tissue-engineered grafts (osteogenic-induced bone mesenchymal stem cells -gelatin) in the rat groin area. Osteogenic activity and inflammatory reactions were assessed using different methods including micro-CT scanning, Alizarin red staining, and immunohistochemical staining.

Results: After one month, in vivo results showed that bone mineralization and inflammatory responses were significantly pronounced in the silicone model or no chamber (control) groups. Vascular perfusion analysis confirmed that the GO-collagen chamber improved the angiogenic processes. Cells labeled with EdU revealed that the GO-collagen chamber promoted the survival and osteogenic differentiation of bone mesenchymal stem cells.

Conclusion: Overall, the novel biocompatible GO-collagen chamber exhibited osteoinductive and anti-fibrosis effects which improved bone regeneration in vivo. It can, therefore, be applied to other fields of regenerative medicine.

Keywords: microenvironment, graphene oxide, tissue engineering chamber, in situ bone regeneration, bone mesenchymal stem cells