Cellular and Molecular Life Sciences

, Volume 76, Issue 3, pp 505–521 | Cite as

The relationship between substrate topography and stem cell differentiation in the musculoskeletal system

  • Jiayun Huang
  • Yangwu Chen
  • Chenqi Tang
  • Yang Fei
  • Haoyu Wu
  • Dengfeng Ruan
  • Maswikiti Ewetse Paul
  • Xiao Chen
  • Zi Yin
  • Boon Chin Heng
  • Weishan Chen
  • Weiliang ShenEmail author


It is well known that biomaterial topography can exert a profound influence on various cellular functions such as migration, polarization, and adhesion. With the development and refinement of manufacturing technology, much research has recently been focused on substrate topography-induced cell differentiation, particularly in the field of tissue engineering. Even without biological and chemical stimuli, the differentiation of stem cells can also be initiated by various biomaterials with different topographic features. However, the underlying mechanisms of this biological phenomenon remain elusive. During the past few decades, many researchers have demonstrated that cells can sense the topography of materials through the assembly and polymerization of membrane proteins. Following the activation of RHO, TGF-b or FAK signaling pathways, cells can be induced into various differentiation states. But these signaling pathways often coincide with canonical mechanical transduction pathways, and no firm conclusion has been reached among researchers in this field on topography-specific signaling pathways. On the other hand, some substrate topographies are reported to have the ability to inhibit differentiation and maintain the ‘stemness’ of stem cells. In this review, we will summarize the role of topography in musculoskeletal system regeneration and explore possible topography-related signaling pathways involved in cell differentiation.


Stem cell differentiation Musculoskeletal system Topography Tissue engineering 



This work of our research group was supported by the National key R&D program of China (2017YFA0104901, 2017YFA0104900), National key research and development program of China (2016YFC1100204), NSFC Grants (81572115, 81874019, 81572157, 81330041, 81125014, 31271041, 81201396, 81271970, J1103603, 81522029, 31570987, 81401781), Regenerative Medicine in Innovative Medical Subjects of Zhejiang Province and Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents, Zhejiang Province Grants (Z2100086, LY12H06006, LR14H060001, LY14H060003), the Key scientific and technological innovation team of Zhejiang Province (2013TD11), Medical and Health Science and Technology Plan of the Department of Health of Zhejiang Province (2013RCA010, 2014KYB052), Medical Science and Technology Project of Zhejiang Province (201341741), and Zhejiang Provisional Grant (2012C33015). International Science and Technology Cooperation Program of China (2015DFG32130). Fundamental Research Funds for the Central Universities. None of the authors had professional or financial affiliations that biased this work.

Compliance with ethical standards

Conflict of interest

The authors hereby declare that they have no conflict of interest.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Jiayun Huang
    • 1
    • 2
    • 3
    • 4
    • 6
  • Yangwu Chen
    • 1
    • 2
    • 3
    • 4
    • 6
  • Chenqi Tang
    • 1
    • 2
    • 3
    • 4
    • 6
  • Yang Fei
    • 1
    • 3
    • 6
  • Haoyu Wu
    • 2
    • 4
  • Dengfeng Ruan
    • 1
    • 3
    • 6
  • Maswikiti Ewetse Paul
    • 2
    • 4
  • Xiao Chen
    • 2
    • 4
    • 6
  • Zi Yin
    • 2
    • 4
  • Boon Chin Heng
    • 5
  • Weishan Chen
    • 1
  • Weiliang Shen
    • 1
    • 2
    • 3
    • 4
    • 6
    Email author
  1. 1.Department of Orthopedic Surgery2nd Affiliated Hospital, School of Medicine, Zhejiang UniversityZhejiangChina
  2. 2.Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang UniversityZhejiangChina
  3. 3.Orthopaedics Research Institute of Zhejiang UniversityZhejiangChina
  4. 4.Department of Sports MedicineSchool of Medicine, Zhejiang UniversityZhejiangChina
  5. 5.Faculty of Dentistry, The University of Hong KongPokfulamChina
  6. 6.China Orthopaedic Regenerative Medicine (CORMed)HangzhouChina

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