Msx1+ stem cells recruited by bioactive tissue engineering graft for bone regeneration

Xianzhu Zhang, Wei Jiang, Chang Xie, Xinyu Wu, Qian Ren, Fei Wang, Xilin Shen, Yi Hong, Hongwei Wu, Youguo Liao, Yi Zhang, Renjie Liang, Wei Sun, Yuqing Gu, Tao Zhang, Yishan Chen, Wei Wei, Shufang Zhang, Weiguo Zou and Hongwei Ouyang ()
Additional contact information
Xianzhu Zhang: Zhejiang University School of Medicine
Wei Jiang: Zhejiang University School of Medicine
Chang Xie: Zhejiang University School of Medicine
Xinyu Wu: Zhejiang University School of Medicine
Qian Ren: University of Chinese Academy of Sciences
Fei Wang: Zhejiang University School of Medicine
Xilin Shen: Zhejiang University School of Medicine
Yi Hong: Zhejiang University School of Medicine
Hongwei Wu: Zhejiang University School of Medicine
Youguo Liao: Zhejiang University School of Medicine
Yi Zhang: Zhejiang University School of Medicine
Renjie Liang: Zhejiang University School of Medicine
Wei Sun: Zhejiang University School of Medicine
Yuqing Gu: Zhejiang University School of Medicine
Tao Zhang: Zhejiang University School of Medicine
Yishan Chen: Zhejiang University School of Medicine
Wei Wei: Zhejiang University School of Medicine
Shufang Zhang: Zhejiang University School of Medicine
Weiguo Zou: University of Chinese Academy of Sciences
Hongwei Ouyang: Zhejiang University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Critical-sized bone defects often lead to non-union and full-thickness defects of the calvarium specifically still present reconstructive challenges. In this study, we show that neurotrophic supplements induce robust in vitro expansion of mesenchymal stromal cells, and in situ transplantation of neurotrophic supplements-incorporated 3D-printed hydrogel grafts promote full-thickness regeneration of critical-sized bone defects. Single-cell RNA sequencing analysis reveals that a unique atlas of in situ stem/progenitor cells is generated during the calvarial bone healing in vivo. Notably, we find a local expansion of resident Msx1+ skeletal stem cells after transplantation of the in situ cell culture system. Moreover, the enhanced calvarial bone regeneration is accompanied by an increased endochondral ossification that closely correlates to the Msx1+ skeletal stem cells. Our findings illustrate the time-saving and regenerative efficacy of in situ cell culture systems targeting major cell subpopulations in vivo for rapid bone tissue regeneration.

Date: 2022
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DOI: 10.1038/s41467-022-32868-y

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