3D bioprinting of multilayered scaffolds with spatially differentiated ADMSCs for rotator cuff tendon-to-bone interface regeneration

Xiping Jiang, Yunfan Kong, Mitchell Kuss, Joel Weisenburger, Hani Haider, Robert Harms, Wen Shi, Bo Liu, Wen Xue, Jianghu Dong, Jingwei Xie, Philipp Streubel, Bin Duan

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Regeneration of the gradient structure of the tendon-to-bone interface is still a significant clinical challenge. This study reports a novel therapeutic method combining three-dimensional (3D) bioprinting and melt electrospinning writing techniques to regenerate a functional tendon-to-bone interface. We generated biomimetic multilayered scaffolds with 3D-bioprinted pre-differentiated autologous adipose-derived mesenchymal stem cells (ADMSC), which recapitulated compositional and cellular structures of the interface. The hydrogel-based bioinks offered high cell viability and proliferative capability for rabbit ADMSCs. The hydrogels with pre-differentiated (into tenogenic, chondrogenic, and osteogenic lineages) or undifferentiated rabbit ADMSCs were 3D-bioprinted into zonal-specific constructs to mimic the structure of the tendon-to-bone interface. These scaffolds were tested in a rabbit rotator cuff injury model and the histological, radiological, and biomechanical changes were analyzed. The in vivo studies demonstrated that the scaffold with spatially differentiated autologous ADMSCs had a superior histological score and improved collagen organization when compared to acellular scaffolds and similar T2 value as the normal interface tissue. The biomechanical characterization demonstrated that the application of multilayered scaffolds improved the biomechanical properties of the tendon-to-bone interface at 12 weeks after rotator cuff reconstruction surgery, but the incorporation of autologous ADMSCs within the multilayered scaffolds showed a limited contribution. Thus, our work provides a 3D-bioprinting-based strategy with the application of autologous ADMSCs to reconstruct massive rotator cuff tendon tears.

Original languageEnglish (US)
Article number101510
JournalApplied Materials Today
StatePublished - Jun 2022


  • Adipose-derived mesenchymal stem cells
  • Direct writing
  • Tendon tissue engineering
  • Tendon-to-bone interface

ASJC Scopus subject areas

  • General Materials Science


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