Novel engineered tendon–fibrocartilage–bone composite with cyclic tension for rotator cuff repair

Qian Liu, Taku Hatta, Jun Qi, Haoyu Liu, Andrew R. Thoreson, Peter C Amadio, Steven Lawrence Moran, Scott P. Steinmann, Anne Gingery, Chunfeng D Zhao

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Surgical repair of rotator cuff tears presents a significant clinical challenge with high failure rates and inferior functional outcomes. Graft augmentation improves repair outcomes; however, currently available grafting materials have limitations. Although cell-seeded decellularized tendon slices may facilitate cell infiltration, promote tendon incorporation, and preserve original mechanical strength, the unique fibrocartilage zone is yet to be successfully reestablished. In this study, we investigated the biological and mechanical properties of an engineered tendon–fibrocartilage–bone composite (TFBC) with cyclic tension (3% strain; 0.2 Hz). Decellularized TFBCs seeded with bone marrow-derived mesenchymal stem cell (BMSCs) sheets and subjected to mechanical stimulation for up to 7 days were characterised by histology, immunohistochemistry, scanning electron microscopy, mechanical testing, and transcriptional regulation. The decellularized TFBC maintained native enthesis structure and properties. Mechanically stimulated TFBC–BMSC constructs displayed increased cell migration after 7 days of culture compared with static groups. The seeded cell sheet not only integrated well with tendon scaffold but also distributed homogeneously and aligned to the direction of stretch under dynamic culture. Developmental genes were regulated including scleraxis, which was significantly upregulated with mechanical stimulation. The Young's modulus of the cell-seeded constructs was significantly higher compared with the noncell-seeded controls. In conclusion, the results of this study reveal that the TFBC–BMSC composite provides an ideal multilayer construct for cell seeding and growth, with mechanical preconditioning further enhances cell penetration and differentiation. The BMSC cell sheet revitalised TFBC in conjunction with mechanical stimulation could serve as a novel and primed biological patch to improve rotator cuff repair.

Original languageEnglish (US)
Pages (from-to)1690-1701
Number of pages12
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2018

Fingerprint

Rotator Cuff
Tendons
Repair
Composite materials
Histology
Mechanical testing
Stem cells
Cell culture
Infiltration
Grafts
Scaffolds
Fibrocartilage
Strength of materials
Developmental Genes
Bone
Multilayers
Genes
Elastic Modulus
Elastic moduli
Mesenchymal Stromal Cells

Keywords

  • bone marrow mesenchymal stem cells
  • bridging patch
  • cell sheet
  • mechanical stimulation
  • rotator cuff repair
  • tissue engineering

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

Cite this

Novel engineered tendon–fibrocartilage–bone composite with cyclic tension for rotator cuff repair. / Liu, Qian; Hatta, Taku; Qi, Jun; Liu, Haoyu; Thoreson, Andrew R.; Amadio, Peter C; Moran, Steven Lawrence; Steinmann, Scott P.; Gingery, Anne; Zhao, Chunfeng D.

In: Journal of Tissue Engineering and Regenerative Medicine, Vol. 12, No. 7, 01.07.2018, p. 1690-1701.

Research output: Contribution to journalArticle

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abstract = "Surgical repair of rotator cuff tears presents a significant clinical challenge with high failure rates and inferior functional outcomes. Graft augmentation improves repair outcomes; however, currently available grafting materials have limitations. Although cell-seeded decellularized tendon slices may facilitate cell infiltration, promote tendon incorporation, and preserve original mechanical strength, the unique fibrocartilage zone is yet to be successfully reestablished. In this study, we investigated the biological and mechanical properties of an engineered tendon–fibrocartilage–bone composite (TFBC) with cyclic tension (3{\%} strain; 0.2 Hz). Decellularized TFBCs seeded with bone marrow-derived mesenchymal stem cell (BMSCs) sheets and subjected to mechanical stimulation for up to 7 days were characterised by histology, immunohistochemistry, scanning electron microscopy, mechanical testing, and transcriptional regulation. The decellularized TFBC maintained native enthesis structure and properties. Mechanically stimulated TFBC–BMSC constructs displayed increased cell migration after 7 days of culture compared with static groups. The seeded cell sheet not only integrated well with tendon scaffold but also distributed homogeneously and aligned to the direction of stretch under dynamic culture. Developmental genes were regulated including scleraxis, which was significantly upregulated with mechanical stimulation. The Young's modulus of the cell-seeded constructs was significantly higher compared with the noncell-seeded controls. In conclusion, the results of this study reveal that the TFBC–BMSC composite provides an ideal multilayer construct for cell seeding and growth, with mechanical preconditioning further enhances cell penetration and differentiation. The BMSC cell sheet revitalised TFBC in conjunction with mechanical stimulation could serve as a novel and primed biological patch to improve rotator cuff repair.",
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