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Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus

Endometrial injury usually results in intrauterine adhesion (IUA), which is an important cause of infertility and recurrent miscarriage in reproductive women. There is still lack of an effective therapeutic strategy to prevent occurrence of IUA. Keratinocyte growth factor (KGF) is a potent repair fa...

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Autores principales: Xu, He-Lin, Xu, Jie, Zhang, Si-Si, Zhu, Qun-Yan, Jin, Bing-Hui, ZhuGe, De-Li, Shen, Bi-Xin, Wu, Xue-Qing, Xiao, Jian, Zhao, Ying-Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241134/
https://www.ncbi.nlm.nih.gov/pubmed/28574291
http://dx.doi.org/10.1080/10717544.2017.1333173
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author Xu, He-Lin
Xu, Jie
Zhang, Si-Si
Zhu, Qun-Yan
Jin, Bing-Hui
ZhuGe, De-Li
Shen, Bi-Xin
Wu, Xue-Qing
Xiao, Jian
Zhao, Ying-Zheng
author_facet Xu, He-Lin
Xu, Jie
Zhang, Si-Si
Zhu, Qun-Yan
Jin, Bing-Hui
ZhuGe, De-Li
Shen, Bi-Xin
Wu, Xue-Qing
Xiao, Jian
Zhao, Ying-Zheng
author_sort Xu, He-Lin
collection PubMed
description Endometrial injury usually results in intrauterine adhesion (IUA), which is an important cause of infertility and recurrent miscarriage in reproductive women. There is still lack of an effective therapeutic strategy to prevent occurrence of IUA. Keratinocyte growth factor (KGF) is a potent repair factor for epithelial tissues. Here, a temperature-sensitive heparin-modified poloxamer (HP) hydrogel with affinity to KGF (KGF-HP) was used as a support matrix to prevent IUA and deliver KGF. The rheology of KGF-HP hydrogel was carefully characterized. The cold KGF-HP solution was rapidly transited to hydrogel with suitable storage modulus (G′) and loss modulus (G″) for the applications of uterus cavity at temperature of 33 °C. In vitro release demonstrated that KGF was released from HP hydrogels in sustained release manner for a long time. In vivo bioluminescence imaging showed that KGF-HP hydrogel was able to prolong the retention of the encapsulated KGF in injured uterus of rat model. Moreover, the morphology and function of the injured uterus were significantly recovered after administration of KGF-HP hydrogel, which were evaluated by two-dimensional ultrasound imaging and receptive fertility. Not only proliferation of endometrial glandular epithelial cells and luminal epithelial cells but also angiogenesis of injured uterus were observed by Ki67 and CD31 staining after 7 d of treatment with KGF-HP hydrogel. Finally, a close relatively relationship between autophagy and proliferation of endometrial epithelial cells (EEC) and angiogenesis was firstly confirmed by detecting expression of LC3-II and P62 after KGF treatment. Overall, KGF-HP may be used as a promising candidate for IUA treatment.
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spelling pubmed-82411342021-07-08 Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus Xu, He-Lin Xu, Jie Zhang, Si-Si Zhu, Qun-Yan Jin, Bing-Hui ZhuGe, De-Li Shen, Bi-Xin Wu, Xue-Qing Xiao, Jian Zhao, Ying-Zheng Drug Deliv Research Article Endometrial injury usually results in intrauterine adhesion (IUA), which is an important cause of infertility and recurrent miscarriage in reproductive women. There is still lack of an effective therapeutic strategy to prevent occurrence of IUA. Keratinocyte growth factor (KGF) is a potent repair factor for epithelial tissues. Here, a temperature-sensitive heparin-modified poloxamer (HP) hydrogel with affinity to KGF (KGF-HP) was used as a support matrix to prevent IUA and deliver KGF. The rheology of KGF-HP hydrogel was carefully characterized. The cold KGF-HP solution was rapidly transited to hydrogel with suitable storage modulus (G′) and loss modulus (G″) for the applications of uterus cavity at temperature of 33 °C. In vitro release demonstrated that KGF was released from HP hydrogels in sustained release manner for a long time. In vivo bioluminescence imaging showed that KGF-HP hydrogel was able to prolong the retention of the encapsulated KGF in injured uterus of rat model. Moreover, the morphology and function of the injured uterus were significantly recovered after administration of KGF-HP hydrogel, which were evaluated by two-dimensional ultrasound imaging and receptive fertility. Not only proliferation of endometrial glandular epithelial cells and luminal epithelial cells but also angiogenesis of injured uterus were observed by Ki67 and CD31 staining after 7 d of treatment with KGF-HP hydrogel. Finally, a close relatively relationship between autophagy and proliferation of endometrial epithelial cells (EEC) and angiogenesis was firstly confirmed by detecting expression of LC3-II and P62 after KGF treatment. Overall, KGF-HP may be used as a promising candidate for IUA treatment. Taylor & Francis 2017-06-02 /pmc/articles/PMC8241134/ /pubmed/28574291 http://dx.doi.org/10.1080/10717544.2017.1333173 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Xu, He-Lin
Xu, Jie
Zhang, Si-Si
Zhu, Qun-Yan
Jin, Bing-Hui
ZhuGe, De-Li
Shen, Bi-Xin
Wu, Xue-Qing
Xiao, Jian
Zhao, Ying-Zheng
Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus
title Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus
title_full Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus
title_fullStr Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus
title_full_unstemmed Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus
title_short Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus
title_sort temperature-sensitive heparin-modified poloxamer hydrogel with affinity to kgf facilitate the morphologic and functional recovery of the injured rat uterus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241134/
https://www.ncbi.nlm.nih.gov/pubmed/28574291
http://dx.doi.org/10.1080/10717544.2017.1333173
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