pp 1-20 | Cite as

Cellular Complexity at the Interface: Challenges in Enthesis Tissue Engineering

  • Isabel Calejo
  • Raquel Costa-Almeida
  • Manuela E. GomesEmail author
Part of the Advances in Experimental Medicine and Biology book series


The complex heterogeneous cellular environment found in tendon-to-bone interface makes this structure a challenge for interface tissue engineering. Orthopedic surgeons still face some problems associated with the formation of fibrotic tissue or re-tear occurring after surgical re-attachment of tendons to the bony insertion or the application of grafts. Unfortunately, an understanding of the cellular component of enthesis lags far behind of other well-known musculoskeletal interfaces, which blocks the development of new treatment options for the healing and regeneration of this multifaceted junction. In this chapter, the main characteristics of tendon and bone cell populations are introduced, followed by a brief description of the interfacial cellular niche, highlighting molecular mechanisms governing tendon-to-bone attachment and mineralization. Finally, we describe and critically assess some challenges faced concerning the use of cell-based strategies in tendon-to-bone healing and regeneration.


Biomarkers Bone Cell Biology Cell-based therapies Enthesis healing/repair Regeneration Tendon 





Anterior cruciate ligament


Alkaline phosphatase


Adipose-derived stem cells


Bone morphogenetic protein


Bone morphogenetic protein receptor 1a


Basic multicellular unit


Bone sialoprotein


Extracellular matrix


Growth and differentiation factors




Integrin binding sialoprotein


Indian hedgehog


Matrix metallopeptidase


Mesenchymal stem cells




Parathyroid hormone-related protein


Runt-related transcription factor 2






Sex-determining region Y-box 9




Tendon-derived stem cells


Transforming growth factor beta receptor II


Transforming growth factor beta


Tendon stem/progenitor cells


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Isabel Calejo
    • 1
    • 2
  • Raquel Costa-Almeida
    • 1
    • 2
  • Manuela E. Gomes
    • 1
    • 2
    • 3
    Email author
  1. 1.3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and BiomimeticsUniversity of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineGuimarãesPortugal
  2. 2.ICVS/3B’s – PT Government Associate LaboratoryBraga/GuimarãesPortugal
  3. 3.The Discoveries Centre for Regenerative and Precision MedicineHeadquarters at University of MinhoGuimarãesPortugal

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