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The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix

Fibrotic diseases, such as Dupuytren’s contracture (DC), involve excess scar tissue formation. The differentiation of fibroblasts into myofibroblasts is a significant mechanism in DC, as it generates tissue contraction in areas without wound openings, leading to the deposition of scar tissue, and ev...

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Autores principales: Doan, K. Tu, Kshetri, Pratiksha, Attamakulsri, Natthapume, Newsome, Derek R., Zhou, Feifan, Murray, Cynthia K., Chen, Wei R., Xu, Gang, Vaughan, Melville B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696429/
https://www.ncbi.nlm.nih.gov/pubmed/31357389
http://dx.doi.org/10.3390/molecules24152713
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author Doan, K. Tu
Kshetri, Pratiksha
Attamakulsri, Natthapume
Newsome, Derek R.
Zhou, Feifan
Murray, Cynthia K.
Chen, Wei R.
Xu, Gang
Vaughan, Melville B.
author_facet Doan, K. Tu
Kshetri, Pratiksha
Attamakulsri, Natthapume
Newsome, Derek R.
Zhou, Feifan
Murray, Cynthia K.
Chen, Wei R.
Xu, Gang
Vaughan, Melville B.
author_sort Doan, K. Tu
collection PubMed
description Fibrotic diseases, such as Dupuytren’s contracture (DC), involve excess scar tissue formation. The differentiation of fibroblasts into myofibroblasts is a significant mechanism in DC, as it generates tissue contraction in areas without wound openings, leading to the deposition of scar tissue, and eventually flexing one or more fingers in a restrictive fashion. Additionally, DC has a high recurrence rate. Previously, we showed that N-dihydrogalactochitosan (GC), an immunostimulant, inhibited myofibroblast differentiation in a DC fibroblast culture. Our goal of this study was to expand our previous study to include other DC and normal cell lines and other chitosan derivatives (GC and single-walled carbon nanotube-conjugated GC) to determine the specific mechanism of inhibition. Derivative-incorporated and vehicle control (water) anchored fibroblast-populated collagen matrices (aFPCM) were used to monitor compaction (anchored matrix height reduction) using microscopy and optical coherence tomography (OCT) for six days. Fibroblasts were unable to compact chitosan derivative aFPCM to the same extent as vehicle control aFPCM in repeated experiments. Similarly, chitosan derivative aFPCM contracted less than control aFPCM when released from anchorage. Proliferative myofibroblasts were identified by the presence of alpha smooth muscle actin via myofibroblast proliferative assay. In all tested conditions, a small percentage of myofibroblasts and proliferative cells were present. However, when aFPCM were treated with transforming growth factor-beta 1 (TGF-β1), all tested samples demonstrated increased myofibroblasts, proliferation, compaction, and contraction. Although compaction and contraction were reduced, there was sufficient tension present in the chitosan derivative aFPCM to allow exogenous stimulation of the myofibroblast phenotype.
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spelling pubmed-66964292019-09-05 The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix Doan, K. Tu Kshetri, Pratiksha Attamakulsri, Natthapume Newsome, Derek R. Zhou, Feifan Murray, Cynthia K. Chen, Wei R. Xu, Gang Vaughan, Melville B. Molecules Article Fibrotic diseases, such as Dupuytren’s contracture (DC), involve excess scar tissue formation. The differentiation of fibroblasts into myofibroblasts is a significant mechanism in DC, as it generates tissue contraction in areas without wound openings, leading to the deposition of scar tissue, and eventually flexing one or more fingers in a restrictive fashion. Additionally, DC has a high recurrence rate. Previously, we showed that N-dihydrogalactochitosan (GC), an immunostimulant, inhibited myofibroblast differentiation in a DC fibroblast culture. Our goal of this study was to expand our previous study to include other DC and normal cell lines and other chitosan derivatives (GC and single-walled carbon nanotube-conjugated GC) to determine the specific mechanism of inhibition. Derivative-incorporated and vehicle control (water) anchored fibroblast-populated collagen matrices (aFPCM) were used to monitor compaction (anchored matrix height reduction) using microscopy and optical coherence tomography (OCT) for six days. Fibroblasts were unable to compact chitosan derivative aFPCM to the same extent as vehicle control aFPCM in repeated experiments. Similarly, chitosan derivative aFPCM contracted less than control aFPCM when released from anchorage. Proliferative myofibroblasts were identified by the presence of alpha smooth muscle actin via myofibroblast proliferative assay. In all tested conditions, a small percentage of myofibroblasts and proliferative cells were present. However, when aFPCM were treated with transforming growth factor-beta 1 (TGF-β1), all tested samples demonstrated increased myofibroblasts, proliferation, compaction, and contraction. Although compaction and contraction were reduced, there was sufficient tension present in the chitosan derivative aFPCM to allow exogenous stimulation of the myofibroblast phenotype. MDPI 2019-07-26 /pmc/articles/PMC6696429/ /pubmed/31357389 http://dx.doi.org/10.3390/molecules24152713 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Doan, K. Tu
Kshetri, Pratiksha
Attamakulsri, Natthapume
Newsome, Derek R.
Zhou, Feifan
Murray, Cynthia K.
Chen, Wei R.
Xu, Gang
Vaughan, Melville B.
The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix
title The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix
title_full The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix
title_fullStr The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix
title_full_unstemmed The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix
title_short The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix
title_sort effect of chitosan derivatives on the compaction and tension generation of the fibroblast-populated collagen matrix
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696429/
https://www.ncbi.nlm.nih.gov/pubmed/31357389
http://dx.doi.org/10.3390/molecules24152713
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