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Implantation of a novel tissue-engineered graft in a large tendon defect initiated inflammation, accelerated fibroplasia and improved remodeling of the new Achilles tendon: a comprehensive detailed study with new insights

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We constructed a new artificial collagen-based graft as a tendon proper and covered it with a polydioxanone sheath. This bioimplant was tested in vitro and also its effectiveness was tested in a large tendon defect model in vivo. A 2-cm full defect in the left Achilles tendon of all animals (n = 120) was created. The animals were andomly divided into three groups: control (n = 40), treated with collagen-based graft (n = 40) and treated with collagen-Polydioxanone-based graft (n = 40). Clinical examination was done weekly. The animals were euthanized at 60 and 120 days post-injury (DPI). The serum level of platelet-derived growth factor (PDGF) was measured. Hydroxyproline and dry matter content together with gross morphologic, histomorphometric, ultrastructural and biomechanical characteristics of the healing tissues were studied. The mechanism of host–graft interactions was studied in another 55 pilot animals. The graft was able to initiate inflammation, accelerate fibroplasia and improve remodeling of the neotenon in the defect area. Except for small remnants, most parts of the implants were gradually absorbed and substituted by a newly regenerated tendon. The preserved remnants were accepted as a part of neotenon and acted as scaffolds for the newly regenerated collagen fibrils. Unlike the controls, the treated lesions showed lower peritendinous adhesion, muscle fibrosis and atrophy and higher hydroxyproline concentration, dry matter content, ultimate strength, yield strength and modulus of elasticity. Numbers, diameter, density and differentiation of collagen fibrils were also greater in the treated lesions than the control ones. This study showed that the implant was cytocompatible, biodegradable, biocompatible and effective in tendon healing.

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Days post-injury


Injured control tendons


Injured treated tendons with collagen implant


Injured treated tendons with collagen implant and polydioxanone sheath


Normal contralateral tendons


Platelet-derived growth factors


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We thank Shiraz University Veterinary School for financial support and cooperation and sincerely appreciate additional funding through grant ISNF 87020247, from the Iranian National Science Foundation. We are also grateful to Dr A. Mogheiseh, Dr N. Golestani, Dr M. Forood, Dr Y. Aryazand (Department of Clinical Sciences) G. Yousefi, L. Shirvani (Deparment of Pathobiology), A. Safavi (Center of Electron Microscopy), M.R. Solhpoor (Department of Materials Science), M. Noroozi, G. Rezaiee and J. Sarikhani (Department of Surgery) from Shiraz University, Shiraz, Iran, for their technical assistance.


This work was supported by the Shiraz University Veterinary School and the Iranian National Science Foundation (grant ISNF 87020247). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors declare that no competing interests exist.

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Correspondence to Ali Moshiri.

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Oryan, A., Moshiri, A. & Meimandi-Parizi, A. Implantation of a novel tissue-engineered graft in a large tendon defect initiated inflammation, accelerated fibroplasia and improved remodeling of the new Achilles tendon: a comprehensive detailed study with new insights. Cell Tissue Res 355, 59–80 (2014). https://doi.org/10.1007/s00441-013-1726-3

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  • Tissue engineering
  • Tendon healing
  • Ultrastructure
  • Reconstructive surgery
  • Collagen
  • Polydioxanone
  • Scaffold
  • Implant
  • Graft