Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit Model

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. Amo...

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Main Authors: Marta Bottagisio, Daniele D’Arrigo, Giuseppe Talò, Matilde Bongio, Marco Ferroni, Federica Boschetti, Matteo Moretti, Arianna B. Lovati
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/5267479
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author Marta Bottagisio
Daniele D’Arrigo
Giuseppe Talò
Matilde Bongio
Marco Ferroni
Federica Boschetti
Matteo Moretti
Arianna B. Lovati
author_facet Marta Bottagisio
Daniele D’Arrigo
Giuseppe Talò
Matilde Bongio
Marco Ferroni
Federica Boschetti
Matteo Moretti
Arianna B. Lovati
author_sort Marta Bottagisio
collection DOAJ
description 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.
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spelling doaj-art-75ceeda1c77645d38391dbd4c0169a3a2025-02-03T06:07:57ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/52674795267479Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit ModelMarta Bottagisio0Daniele D’Arrigo1Giuseppe Talò2Matilde Bongio3Marco Ferroni4Federica Boschetti5Matteo Moretti6Arianna B. Lovati7Laboratory of Clinical Chemistry and Microbiology, IRCCS Istituto Ortopedico Galeazzi, Milan 20161, ItalyCell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Milan 20161, ItalyCell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Milan 20161, ItalyCell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Milan 20161, ItalyDepartment of Chemistry, Materials and Chemical Engineering Giulio Natta, Politecnico di Milano, Milan 20133, ItalyDepartment of Chemistry, Materials and Chemical Engineering Giulio Natta, Politecnico di Milano, Milan 20133, ItalyCell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Milan 20161, ItalyCell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Milan 20161, ItalyTendon 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.http://dx.doi.org/10.1155/2019/5267479
spellingShingle Marta Bottagisio
Daniele D’Arrigo
Giuseppe Talò
Matilde Bongio
Marco Ferroni
Federica Boschetti
Matteo Moretti
Arianna B. Lovati
Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit Model
Stem Cells International
title Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit Model
title_full Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit Model
title_fullStr Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit Model
title_full_unstemmed Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit Model
title_short Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit Model
title_sort achilles tendon repair by decellularized and engineered xenografts in a rabbit model
url http://dx.doi.org/10.1155/2019/5267479
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