Journal of Zhejiang University

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Force-controlled 3D mechanical stretching to enhance the exosome secretion of bone mesenchymal stem cells for bone repair

Author(s): Jie Wu , Hao Wang , Tao Sun, Qing Shi, Xie Chen, Yuanbo Qi, Sheng Tao, Jiahua Zhao, Daohong Liu
Affiliation(s): Department of Orthopedics, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100142, People’s Republic of China; Department of Orthopedics, The Eighth Medical Center of Chinese PLA General Hospital, Beijing 100091, People’s Republic of China; Department of Orthopaedics, Lanzhou University Second Hospital, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, People’s Republic of China; Intelligent Robotics Institute, School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, People’s Republic of China; Department of Thoracic Surgery, The Sixth Medical Center, Chinese PLA General Hospital, Beijing,100048, People’s Republic of China; Corresponding authors at: Department of Orthopedics, Chinese PLA General Hospital, Beijing 100853, China.
Corresponding email(s): jiahua301@163.com (J. Zhao), domb@vip.sina.com (D. Liu)
Key Words: exosomes, force control, mechanical loading, mesenchymal stem cells, bone repair

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Jie Wu , Hao Wang , Tao Sun, Qing Shi, Xie Chen, Yuanbo Qi, Sheng Tao, Jiahua Zhao, Daohong Liu. Force-controlled 3D mechanical stretching to enhance the exosome secretion of bone mesenchymal stem cells for bone repair[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/bdm.2400231

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%J Journal of Zhejiang University SCIENCE B
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doi="https://doi.org/10.1631/bdm.2400231"

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A1 - Tao Sun
A1 - Qing Shi
A1 - Xie Chen
A1 - Yuanbo Qi
A1 - Sheng Tao
A1 - Jiahua Zhao
A1 - Daohong Liu
J0 - Journal of Zhejiang University Science B
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Y1 - in press
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doi="https://doi.org/10.1631/bdm.2400231"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: exosomes derived from bone marrow mesenchymal stem cells (BMSCs) show promising potential in the treatment of bone defects. However, their clinical application has been hindered by low yield and insufficient repair ability. Mechanical stimulation in 3D has been a well-known method to enhance exosome secretion, however, the traditional stimulation process was always achieved by controlling the displacement of manipulator, which may induce uneven loading distribution and degradation of stimulation strength. Here, we proposed a micro-stretching manipulator with a capacity of automatically controlling the stretching force applied to GelMA/HAMA hybrid hydrogel sheets containing BMSCs within an incubator. To ensure structural stability of the sheets after long-term stretching, the mixing ratio of GelMA and HAMA was optimized according to the mechanical property response of the sheets to cyclical loading. Subsequently, a force-controlled mechanical loading was applied to the BMSC-laden sheets in order to produce exosomes. Compare with the control for displacement, force-controlled loading has been demonstrated to provide a more stable force stimulation, thereby enhancing the secretion of exosomes. Furthermore, continuously stimulated exosomes have exhibited a more potent capacity in promoting the osteogenic differentiation of BMSCs and facilitating the repair of bone defects in a rat model. These findings suggest that force-controlled loading for cell-laden hydrogel offers a novel approach for the production of BMSC-exos and their application in bone repair

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On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 0000-00-00

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Citations: Bibtex RefMan EndNote GB/T7714

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