Achilles tendon repair by decellularized and engineered xenografts in a rabbit model

Marta Bottagisio, Daniele D'Arrigo, Giuseppe Talò, Matilde Bongio, Marco Ferroni, Federica Boschetti, Matteo Moretti, Arianna B. Lovati

Research output: Contribution to journalArticle

Abstract

Tendon tissue ruptures often require the replacement of damaged tissues. The use of auto- or allografts is notoriously limited due to the scarce supply and the high risks of immune adverse reactions. To overcome these limitations, tissue engineering (TE) has been considered a promising approach. Among several biomaterials, decellularized xenografts are available in large quantity and could represent a possible solution for tendon reconstruction. The present study is aimed at evaluating TE xenografts in Achilles tendon defects. Specifically, the ability to enhance the biomechanical functionality, while improving the graft interaction with the host, was tested. The combination of decellularized equine-derived tendon xenografts with or without the matrix repopulation with autologous bone marrow mesenchymal stem cells (BMSCs) under stretch-perfusion dynamic conditions might improve the side-to-side tendon reconstruction. Thirty-six New Zealand rabbits were used to create 2 cm long segmental defects of the Achilles tendon. Then, animals were implanted with autograft (AG) as the gold standard control, decellularized graft (DG), or in vitro tissue-engineered graft (TEG) and evaluated postoperatively at 12 weeks. After sacrifice, histological, immunohistochemical, biochemical, and biomechanical analyses were performed along with the matrix metalloproteinases. The results demonstrated the beneficial role of undifferentiated BMSCs loaded within decellularized xenografts undergoing a stretch-perfusion culture as an immunomodulatory weapon reducing the inflammatory process. Interestingly, AG and TEG groups exhibited similar results, behaved similarly, and showed a significant superior tissue healing compared to DG in terms of newly formed collagen fibres and biomechanical parameters. Whereas, DG demonstrated a massive inflammatory and giant cell response associated with graft destruction and necrosis, absence of type I and III collagen, and a higher amount of proteoglycans and MMP-2, thus unfavourably affecting the biomechanical response. In conclusion, this in vivo study suggests a potential use of the proposed tissue-engineered constructs for tendon reconstruction.

Original languageEnglish
Article number5267479
JournalStem Cells International
Volume2019
DOIs
Publication statusPublished - Jan 1 2019

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Achilles Tendon
Heterografts
Rabbits
Tendons
Transplants
Autografts
Tissue Engineering
Matrix Metalloproteinases
Mesenchymal Stromal Cells
Perfusion
Bone Marrow
Weapons
Collagen Type III
Biocompatible Materials
Proteoglycans
Giant Cells
Collagen Type I
Horses
Allografts
Rupture

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Bottagisio, M., D'Arrigo, D., Talò, G., Bongio, M., Ferroni, M., Boschetti, F., ... Lovati, A. B. (2019). Achilles tendon repair by decellularized and engineered xenografts in a rabbit model. Stem Cells International, 2019, [5267479]. https://doi.org/10.1155/2019/5267479

Achilles tendon repair by decellularized and engineered xenografts in a rabbit model. / Bottagisio, Marta; D'Arrigo, Daniele; Talò, Giuseppe; Bongio, Matilde; Ferroni, Marco; Boschetti, Federica; Moretti, Matteo; Lovati, Arianna B.

In: Stem Cells International, Vol. 2019, 5267479, 01.01.2019.

Research output: Contribution to journalArticle

Bottagisio, Marta ; D'Arrigo, Daniele ; Talò, Giuseppe ; Bongio, Matilde ; Ferroni, Marco ; Boschetti, Federica ; Moretti, Matteo ; Lovati, Arianna B. / Achilles tendon repair by decellularized and engineered xenografts in a rabbit model. In: Stem Cells International. 2019 ; Vol. 2019.
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