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Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair

[Image: see text] There is an urgent need for improved outcomes in the treatment of pelvic organ prolapse (POP). Success of primary surgery relies on the load bearing capacity of plicated connective tissue underneath the vaginal wall, which is compromised due to an altered vaginal fibroblast functio...

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Autores principales: Gudde, Aksel N., van Velthoven, Melissa J. J., Türkel, Betül, Kouwer, Paul H. J., Roovers, Jan-Paul W. R., Guler, Zeliha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521013/
https://www.ncbi.nlm.nih.gov/pubmed/37589427
http://dx.doi.org/10.1021/acsabm.3c00433
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author Gudde, Aksel N.
van Velthoven, Melissa J. J.
Türkel, Betül
Kouwer, Paul H. J.
Roovers, Jan-Paul W. R.
Guler, Zeliha
author_facet Gudde, Aksel N.
van Velthoven, Melissa J. J.
Türkel, Betül
Kouwer, Paul H. J.
Roovers, Jan-Paul W. R.
Guler, Zeliha
author_sort Gudde, Aksel N.
collection PubMed
description [Image: see text] There is an urgent need for improved outcomes in the treatment of pelvic organ prolapse (POP). Success of primary surgery relies on the load bearing capacity of plicated connective tissue underneath the vaginal wall, which is compromised due to an altered vaginal fibroblast function and collagen composition. There is an important factor in connective tissue repair that relates to changes in stiffness of the vaginal fibroblast microenvironment, which influences cell activity through cellular mechanosensing. The aim of this study is to investigate the effect of stiffness changes on vaginal fibroblast functions that relate to connective tissue healing in prolapse repair. The substrate stiffness was controlled by changing the polymer concentration in the fibrous and strongly biomimetic polyisocyanide (PIC) hydrogel. We analyzed stiffness during cell culture and assessed the consequential fibroblast proliferation, morphology, collagen deposition, and contraction. Our results show that increasing stiffness coincides with vaginal fibroblast alignment, promotes collagen deposition, and inhibits PIC gel contraction. These findings suggest that the matrix stiffness directly influences vaginal fibroblast functionality. Moreover, we observed a buildup in stiffness and collagen, with an enhanced fibroblast and collagen organization on the PIC-substrate, which indicate an enhanced structural integrity of the hydrogel-cell construct. An improved tissue structure during healing is relevant in the functional repair of POP. Therefore, this study encourages future research in the use of PIC gels as a supplement in prolapse surgery, whereby the hydrogel stiffness should be considered.
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spelling pubmed-105210132023-09-27 Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair Gudde, Aksel N. van Velthoven, Melissa J. J. Türkel, Betül Kouwer, Paul H. J. Roovers, Jan-Paul W. R. Guler, Zeliha ACS Appl Bio Mater [Image: see text] There is an urgent need for improved outcomes in the treatment of pelvic organ prolapse (POP). Success of primary surgery relies on the load bearing capacity of plicated connective tissue underneath the vaginal wall, which is compromised due to an altered vaginal fibroblast function and collagen composition. There is an important factor in connective tissue repair that relates to changes in stiffness of the vaginal fibroblast microenvironment, which influences cell activity through cellular mechanosensing. The aim of this study is to investigate the effect of stiffness changes on vaginal fibroblast functions that relate to connective tissue healing in prolapse repair. The substrate stiffness was controlled by changing the polymer concentration in the fibrous and strongly biomimetic polyisocyanide (PIC) hydrogel. We analyzed stiffness during cell culture and assessed the consequential fibroblast proliferation, morphology, collagen deposition, and contraction. Our results show that increasing stiffness coincides with vaginal fibroblast alignment, promotes collagen deposition, and inhibits PIC gel contraction. These findings suggest that the matrix stiffness directly influences vaginal fibroblast functionality. Moreover, we observed a buildup in stiffness and collagen, with an enhanced fibroblast and collagen organization on the PIC-substrate, which indicate an enhanced structural integrity of the hydrogel-cell construct. An improved tissue structure during healing is relevant in the functional repair of POP. Therefore, this study encourages future research in the use of PIC gels as a supplement in prolapse surgery, whereby the hydrogel stiffness should be considered. American Chemical Society 2023-08-17 /pmc/articles/PMC10521013/ /pubmed/37589427 http://dx.doi.org/10.1021/acsabm.3c00433 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Gudde, Aksel N.
van Velthoven, Melissa J. J.
Türkel, Betül
Kouwer, Paul H. J.
Roovers, Jan-Paul W. R.
Guler, Zeliha
Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair
title Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair
title_full Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair
title_fullStr Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair
title_full_unstemmed Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair
title_short Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair
title_sort vaginal fibroblast behavior as a function of stiffness changes in a polyisocyanide hydrogel for prolapse repair
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521013/
https://www.ncbi.nlm.nih.gov/pubmed/37589427
http://dx.doi.org/10.1021/acsabm.3c00433
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