Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications

Structural cardiac lesions are often surgically repaired using prosthetic patches, which can be biological or synthetic. In the current clinical scenario, biological patches derived from the decellularization of a xenogeneic scaffold are gaining more interest as they maintain the natural architectur...

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Main Authors: Tiziana Palmosi, Anna Maria Tolomeo, Carmine Cirillo, Debora Sandrin, Manuela Sciro, Susanna Negrisolo, Martina Todesco, Federico Caicci, Michele Santoro, Eleonora Dal Lago, Massimo Marchesan, Michele Modesti, Andrea Bagno, Filippo Romanato, Paolo Grumati, Assunta Fabozzo, Gino Gerosa
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2022.1042434/full
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author Tiziana Palmosi
Tiziana Palmosi
Anna Maria Tolomeo
Anna Maria Tolomeo
Carmine Cirillo
Debora Sandrin
Debora Sandrin
Manuela Sciro
Susanna Negrisolo
Martina Todesco
Martina Todesco
Federico Caicci
Michele Santoro
Eleonora Dal Lago
Massimo Marchesan
Michele Modesti
Andrea Bagno
Andrea Bagno
Filippo Romanato
Filippo Romanato
Paolo Grumati
Paolo Grumati
Assunta Fabozzo
Assunta Fabozzo
Gino Gerosa
Gino Gerosa
Gino Gerosa
author_facet Tiziana Palmosi
Tiziana Palmosi
Anna Maria Tolomeo
Anna Maria Tolomeo
Carmine Cirillo
Debora Sandrin
Debora Sandrin
Manuela Sciro
Susanna Negrisolo
Martina Todesco
Martina Todesco
Federico Caicci
Michele Santoro
Eleonora Dal Lago
Massimo Marchesan
Michele Modesti
Andrea Bagno
Andrea Bagno
Filippo Romanato
Filippo Romanato
Paolo Grumati
Paolo Grumati
Assunta Fabozzo
Assunta Fabozzo
Gino Gerosa
Gino Gerosa
Gino Gerosa
author_sort Tiziana Palmosi
collection DOAJ
description Structural cardiac lesions are often surgically repaired using prosthetic patches, which can be biological or synthetic. In the current clinical scenario, biological patches derived from the decellularization of a xenogeneic scaffold are gaining more interest as they maintain the natural architecture of the extracellular matrix (ECM) after the removal of the native cells and remnants. Once implanted in the host, these patches can induce tissue regeneration and repair, encouraging angiogenesis, migration, proliferation, and host cell differentiation. Lastly, decellularized xenogeneic patches undergo cell repopulation, thus reducing host immuno-mediated response against the graft and preventing device failure. Porcine small intestinal submucosa (pSIS) showed such properties in alternative clinical scenarios. Specifically, the US FDA approved its use in humans for urogenital procedures such as hernia repair, cystoplasties, ureteral reconstructions, stress incontinence, Peyronie’s disease, penile chordee, and even urethral reconstruction for hypospadias and strictures. In addition, it has also been successfully used for skeletal muscle tissue reconstruction in young patients. However, for cardiovascular applications, the results are controversial. In this study, we aimed to validate our decellularization protocol for SIS, which is based on the use of Tergitol 15 S 9, by comparing it to our previous and efficient method (Triton X 100), which is not more available in the market. For both treatments, we evaluated the preservation of the ECM ultrastructure, biomechanical features, biocompatibility, and final bioinductive capabilities. The overall analysis shows that the SIS tissue is macroscopically distinguishable into two regions, one smooth and one wrinkle, equivalent to the ultrastructure and biochemical and proteomic profile. Furthermore, Tergitol 15 S 9 treatment does not modify tissue biomechanics, resulting in comparable to the native one and confirming the superior preservation of the collagen fibers. In summary, the present study showed that the SIS decellularized with Tergitol 15 S 9 guarantees higher performances, compared to the Triton X 100 method, in all the explored fields and for both SIS regions: smooth and wrinkle.
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spelling doaj.art-2072095a05d54f55846b45390af5479b2022-12-22T03:50:57ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-12-011010.3389/fbioe.2022.10424341042434Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applicationsTiziana Palmosi0Tiziana Palmosi1Anna Maria Tolomeo2Anna Maria Tolomeo3Carmine Cirillo4Debora Sandrin5Debora Sandrin6Manuela Sciro7Susanna Negrisolo8Martina Todesco9Martina Todesco10Federico Caicci11Michele Santoro12Eleonora Dal Lago13Massimo Marchesan14Michele Modesti15Andrea Bagno16Andrea Bagno17Filippo Romanato18Filippo Romanato19Paolo Grumati20Paolo Grumati21Assunta Fabozzo22Assunta Fabozzo23Gino Gerosa24Gino Gerosa25Gino Gerosa26Laboratory of Cardiovascular Medicine, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, ItalyLaboratory of Cardiovascular Medicine, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, ItalyOptics and Bioimaging Lab, Department of Physics and Astronomy, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, University of Padova, Padua, ItalyAzienda Ospedale Padova, Padua, ItalyLaboratory of Immunopathology and Molecular Biology of the Kidney, Department of Women’s and Children’s Health, University of Padova, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, ItalyDepartment of Industrial Engineering, University of Padova, Padua, ItalyDepartment of Biology, University of Padova, Padua, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, ItalyDepartment of Industrial Engineering, University of Padova, Padua, ItalyConsultant of Animal and Food Welfare, Padua, ItalyDepartment of Industrial Engineering, University of Padova, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, ItalyDepartment of Industrial Engineering, University of Padova, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy0Department of Physics and Astronomy “G. Galilei”, University of Padova, Padua, ItalyTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy1Department of Clinical Medicine and Surgery, University of Napoli Federico II, Naples, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy2Cardiac Surgery Unit, Hospital University of Padova, Padua, ItalyLaboratory of Cardiovascular Medicine, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy2Cardiac Surgery Unit, Hospital University of Padova, Padua, ItalyStructural cardiac lesions are often surgically repaired using prosthetic patches, which can be biological or synthetic. In the current clinical scenario, biological patches derived from the decellularization of a xenogeneic scaffold are gaining more interest as they maintain the natural architecture of the extracellular matrix (ECM) after the removal of the native cells and remnants. Once implanted in the host, these patches can induce tissue regeneration and repair, encouraging angiogenesis, migration, proliferation, and host cell differentiation. Lastly, decellularized xenogeneic patches undergo cell repopulation, thus reducing host immuno-mediated response against the graft and preventing device failure. Porcine small intestinal submucosa (pSIS) showed such properties in alternative clinical scenarios. Specifically, the US FDA approved its use in humans for urogenital procedures such as hernia repair, cystoplasties, ureteral reconstructions, stress incontinence, Peyronie’s disease, penile chordee, and even urethral reconstruction for hypospadias and strictures. In addition, it has also been successfully used for skeletal muscle tissue reconstruction in young patients. However, for cardiovascular applications, the results are controversial. In this study, we aimed to validate our decellularization protocol for SIS, which is based on the use of Tergitol 15 S 9, by comparing it to our previous and efficient method (Triton X 100), which is not more available in the market. For both treatments, we evaluated the preservation of the ECM ultrastructure, biomechanical features, biocompatibility, and final bioinductive capabilities. The overall analysis shows that the SIS tissue is macroscopically distinguishable into two regions, one smooth and one wrinkle, equivalent to the ultrastructure and biochemical and proteomic profile. Furthermore, Tergitol 15 S 9 treatment does not modify tissue biomechanics, resulting in comparable to the native one and confirming the superior preservation of the collagen fibers. In summary, the present study showed that the SIS decellularized with Tergitol 15 S 9 guarantees higher performances, compared to the Triton X 100 method, in all the explored fields and for both SIS regions: smooth and wrinkle.https://www.frontiersin.org/articles/10.3389/fbioe.2022.1042434/fullcardiac repairdecellularizationcardiac surgeryECMextracellular matrixSIS
spellingShingle Tiziana Palmosi
Tiziana Palmosi
Anna Maria Tolomeo
Anna Maria Tolomeo
Carmine Cirillo
Debora Sandrin
Debora Sandrin
Manuela Sciro
Susanna Negrisolo
Martina Todesco
Martina Todesco
Federico Caicci
Michele Santoro
Eleonora Dal Lago
Massimo Marchesan
Michele Modesti
Andrea Bagno
Andrea Bagno
Filippo Romanato
Filippo Romanato
Paolo Grumati
Paolo Grumati
Assunta Fabozzo
Assunta Fabozzo
Gino Gerosa
Gino Gerosa
Gino Gerosa
Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications
Frontiers in Bioengineering and Biotechnology
cardiac repair
decellularization
cardiac surgery
ECM
extracellular matrix
SIS
title Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications
title_full Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications
title_fullStr Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications
title_full_unstemmed Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications
title_short Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications
title_sort small intestinal submucosa derived extracellular matrix as a heterotopic scaffold for cardiovascular applications
topic cardiac repair
decellularization
cardiac surgery
ECM
extracellular matrix
SIS
url https://www.frontiersin.org/articles/10.3389/fbioe.2022.1042434/full
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