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Related Experiment Video

Updated: Aug 12, 2025

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Sandwich Biomimetic Scaffold Based Tendon Stem/Progenitor Cell Alignment in a 3D Microenvironment for Functional

Sihao Li1,2,3,4, Yuan Sun5,6, Yazhou Chen1,2,3,4

  • 1Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.

ACS Applied Materials & Interfaces
|January 26, 2023
PubMed
Summary

This study developed a 3D biomimetic model for tendon regeneration. The 3D-aligned tendon stem/progenitor cells (TSPCs) enhanced differentiation and promoted healing in vivo.

Keywords:
regenerationstem celltendonthree-dimensionaltopology

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Tissue Engineering

Background:

  • Tendon injuries are common musculoskeletal issues impacting regeneration.
  • Cellular microenvironment and scaffold topology significantly influence tendon healing.
  • Exploring three-dimensional (3D) cellular interactions within ordered structures is crucial for developing effective tendon substitutes.

Purpose of the Study:

  • To investigate the cellular response and regenerative potential of tendon stem/progenitor cells (TSPCs) within a 3D-aligned biomimetic microenvironment.
  • To compare the tenogenic differentiation and inflammatory response of TSPCs in 3D versus 2D models.
  • To evaluate the in vivo efficacy of 3D-aligned TSPCs for promoting tendon regeneration and preventing heterotopic ossification.

Main Methods:

  • Fabrication of an ordered 3D sandwich model using high-resolution 3D printing to create parallel-grooved topographical cues on a hydrogel.
  • Seeding of TSPCs onto the hydrogel surface to create a 2D model, followed by hydrogel coating to form the 3D model.
  • Assessment of cell ordering, tenogenic differentiation via the PI3K-AKT pathway, inflammatory markers, and in vivo implantation in an Achilles defect model.

Main Results:

  • TSPCs maintained ordered growth in the 3D model, similar to the 2D model.
  • 3D-aligned TSPCs demonstrated enhanced tenogenic differentiation through the PI3K-AKT signaling pathway.
  • The 3D-aligned TSPC composite promoted tendon regeneration and reduced heterotopic ossification in vivo, with a less inflammatory phenotype compared to the 2D model.

Conclusions:

  • A 3D-aligned biomimetic microenvironment supports ordered cell growth and enhances tenogenic differentiation.
  • 3D-aligned TSPCs show reduced inflammation and improved in vivo tendon regeneration.
  • This 3D-aligned TSPC approach holds promise for functional tendon repair and regeneration strategies.