Comprehensive ex vivo and in vivo preclinical evaluation of novel chemo enzymatic decellularized peripheral nerve allografts

As a reliable alternative to autografts, decellularized peripheral nerve allografts (DPNAs) should mimic the complex microstructure of native nerves and be immunogenically compatible. Nevertheless, there is a current lack of decellularization methods able to remove peripheral nerve cells without sig...

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Main Authors: Óscar Darío García-García, Marwa El Soury, Fernando Campos, David Sánchez-Porras, Stefano Geuna, Miguel Alaminos, Giovanna Gambarotta, Jesús Chato-Astrain, Stefania Raimondo, Víctor Carriel
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2023.1162684/full
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author Óscar Darío García-García
Óscar Darío García-García
Óscar Darío García-García
Marwa El Soury
Marwa El Soury
Fernando Campos
David Sánchez-Porras
Stefano Geuna
Miguel Alaminos
Giovanna Gambarotta
Jesús Chato-Astrain
Stefania Raimondo
Víctor Carriel
author_facet Óscar Darío García-García
Óscar Darío García-García
Óscar Darío García-García
Marwa El Soury
Marwa El Soury
Fernando Campos
David Sánchez-Porras
Stefano Geuna
Miguel Alaminos
Giovanna Gambarotta
Jesús Chato-Astrain
Stefania Raimondo
Víctor Carriel
author_sort Óscar Darío García-García
collection DOAJ
description As a reliable alternative to autografts, decellularized peripheral nerve allografts (DPNAs) should mimic the complex microstructure of native nerves and be immunogenically compatible. Nevertheless, there is a current lack of decellularization methods able to remove peripheral nerve cells without significantly altering the nerve extracellular matrix (ECM). The aims of this study are firstly to characterize ex vivo, in a histological, biochemical, biomechanical and ultrastructural way, three novel chemical-enzymatic decellularization protocols (P1, P2 and P3) in rat sciatic nerves and compared with the Sondell classic decellularization method and then, to select the most promising DPNAs to be tested in vivo. All the DPNAs generated present an efficient removal of the cellular material and myelin, while preserving the laminin and collagen network of the ECM (except P3) and were free from any significant alterations in the biomechanical parameters and biocompatibility properties. Then, P1 and P2 were selected to evaluate their regenerative effectivity and were compared with Sondell and autograft techniques in an in vivo model of sciatic defect with a 10-mm gap, after 15 weeks of follow-up. All study groups showed a partial motor and sensory recovery that were in correlation with the histological, histomorphometrical and ultrastructural analyses of nerve regeneration, being P2 the protocol showing the most similar results to the autograft control group.
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spelling doaj.art-ce75750624904a4c861509cd116e00ce2023-04-04T09:53:39ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-03-011110.3389/fbioe.2023.11626841162684Comprehensive ex vivo and in vivo preclinical evaluation of novel chemo enzymatic decellularized peripheral nerve allograftsÓscar Darío García-García0Óscar Darío García-García1Óscar Darío García-García2Marwa El Soury3Marwa El Soury4Fernando Campos5David Sánchez-Porras6Stefano Geuna7Miguel Alaminos8Giovanna Gambarotta9Jesús Chato-Astrain10Stefania Raimondo11Víctor Carriel12Tissue Engineering Group, Department of Histology, University of Granada and Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, SpainDoctoral Program in Biomedicine, University of Granada, Granada, SpainDepartment of Clinical and Biological Sciences and Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, Orbassano, ItalyTissue Engineering Group, Department of Histology, University of Granada and Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, SpainDepartment of Clinical and Biological Sciences and Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, Orbassano, ItalyTissue Engineering Group, Department of Histology, University of Granada and Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, SpainTissue Engineering Group, Department of Histology, University of Granada and Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, SpainDepartment of Clinical and Biological Sciences and Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, Orbassano, ItalyTissue Engineering Group, Department of Histology, University of Granada and Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, SpainDepartment of Clinical and Biological Sciences and Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, Orbassano, ItalyTissue Engineering Group, Department of Histology, University of Granada and Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, SpainDepartment of Clinical and Biological Sciences and Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, Orbassano, ItalyTissue Engineering Group, Department of Histology, University of Granada and Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, SpainAs a reliable alternative to autografts, decellularized peripheral nerve allografts (DPNAs) should mimic the complex microstructure of native nerves and be immunogenically compatible. Nevertheless, there is a current lack of decellularization methods able to remove peripheral nerve cells without significantly altering the nerve extracellular matrix (ECM). The aims of this study are firstly to characterize ex vivo, in a histological, biochemical, biomechanical and ultrastructural way, three novel chemical-enzymatic decellularization protocols (P1, P2 and P3) in rat sciatic nerves and compared with the Sondell classic decellularization method and then, to select the most promising DPNAs to be tested in vivo. All the DPNAs generated present an efficient removal of the cellular material and myelin, while preserving the laminin and collagen network of the ECM (except P3) and were free from any significant alterations in the biomechanical parameters and biocompatibility properties. Then, P1 and P2 were selected to evaluate their regenerative effectivity and were compared with Sondell and autograft techniques in an in vivo model of sciatic defect with a 10-mm gap, after 15 weeks of follow-up. All study groups showed a partial motor and sensory recovery that were in correlation with the histological, histomorphometrical and ultrastructural analyses of nerve regeneration, being P2 the protocol showing the most similar results to the autograft control group.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1162684/fullacellular graftdecellularizationdecellularized nerve allograftperipheral nerve repairtissue engineering
spellingShingle Óscar Darío García-García
Óscar Darío García-García
Óscar Darío García-García
Marwa El Soury
Marwa El Soury
Fernando Campos
David Sánchez-Porras
Stefano Geuna
Miguel Alaminos
Giovanna Gambarotta
Jesús Chato-Astrain
Stefania Raimondo
Víctor Carriel
Comprehensive ex vivo and in vivo preclinical evaluation of novel chemo enzymatic decellularized peripheral nerve allografts
Frontiers in Bioengineering and Biotechnology
acellular graft
decellularization
decellularized nerve allograft
peripheral nerve repair
tissue engineering
title Comprehensive ex vivo and in vivo preclinical evaluation of novel chemo enzymatic decellularized peripheral nerve allografts
title_full Comprehensive ex vivo and in vivo preclinical evaluation of novel chemo enzymatic decellularized peripheral nerve allografts
title_fullStr Comprehensive ex vivo and in vivo preclinical evaluation of novel chemo enzymatic decellularized peripheral nerve allografts
title_full_unstemmed Comprehensive ex vivo and in vivo preclinical evaluation of novel chemo enzymatic decellularized peripheral nerve allografts
title_short Comprehensive ex vivo and in vivo preclinical evaluation of novel chemo enzymatic decellularized peripheral nerve allografts
title_sort comprehensive ex vivo and in vivo preclinical evaluation of novel chemo enzymatic decellularized peripheral nerve allografts
topic acellular graft
decellularization
decellularized nerve allograft
peripheral nerve repair
tissue engineering
url https://www.frontiersin.org/articles/10.3389/fbioe.2023.1162684/full
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