Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration

Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to b...

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Main Authors: Wendell Q Sun, Hui Xu, Maryellen Sandor, Jared Lombardi
Format: Article
Language:English
Published: SAGE Publishing 2013-09-01
Series:Journal of Tissue Engineering
Online Access:https://doi.org/10.1177/2041731413505305
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spelling doaj-82b786043e1c40c9b6da4eff951924402020-11-25T03:36:31ZengSAGE PublishingJournal of Tissue Engineering2041-73142013-09-01410.1177/204173141350530510.1177_2041731413505305Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regenerationWendell Q Sun0Hui Xu1Maryellen Sandor2Jared Lombardi3LifeCell Corporation, Bridgewater, NJ, USALifeCell Corporation, Bridgewater, NJ, USALifeCell Corporation, Bridgewater, NJ, USALifeCell Corporation, Bridgewater, NJ, USAExtracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of extracellular matrix products and bioscaffolds of tissue engineering.https://doi.org/10.1177/2041731413505305
collection DOAJ
language English
format Article
sources DOAJ
author Wendell Q Sun
Hui Xu
Maryellen Sandor
Jared Lombardi
spellingShingle Wendell Q Sun
Hui Xu
Maryellen Sandor
Jared Lombardi
Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration
Journal of Tissue Engineering
author_facet Wendell Q Sun
Hui Xu
Maryellen Sandor
Jared Lombardi
author_sort Wendell Q Sun
title Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration
title_short Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration
title_full Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration
title_fullStr Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration
title_full_unstemmed Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration
title_sort process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration
publisher SAGE Publishing
series Journal of Tissue Engineering
issn 2041-7314
publishDate 2013-09-01
description Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of extracellular matrix products and bioscaffolds of tissue engineering.
url https://doi.org/10.1177/2041731413505305
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