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KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats

OBJECTIVE: The present study focused on the development of a poloxamer 407 thermosensitive hydrogel loaded with keratinocyte growth factor-2 (KGF-2) and fibroblast growth factor-21 (FGF-21) as a therapeutic biomaterial in a scald-wound model of type-2 diabetes in Goto-Kakizaki (GK) rats. RESEARCH DE...

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Autores principales: Yang, Xuanxin, Yang, Rongshuai, Chen, Min, Zhou, Qingde, Zheng, Yingying, Lu, Chao, Bi, Jianing, Sun, Wenzhe, Huang, Tongzhou, Li, Lijia, Gong, Jianxiang, Li, Xiaokun, Hui, Qi, Wang, Xiaojie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245451/
https://www.ncbi.nlm.nih.gov/pubmed/32434772
http://dx.doi.org/10.1136/bmjdrc-2019-001009
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author Yang, Xuanxin
Yang, Rongshuai
Chen, Min
Zhou, Qingde
Zheng, Yingying
Lu, Chao
Bi, Jianing
Sun, Wenzhe
Huang, Tongzhou
Li, Lijia
Gong, Jianxiang
Li, Xiaokun
Hui, Qi
Wang, Xiaojie
author_facet Yang, Xuanxin
Yang, Rongshuai
Chen, Min
Zhou, Qingde
Zheng, Yingying
Lu, Chao
Bi, Jianing
Sun, Wenzhe
Huang, Tongzhou
Li, Lijia
Gong, Jianxiang
Li, Xiaokun
Hui, Qi
Wang, Xiaojie
author_sort Yang, Xuanxin
collection PubMed
description OBJECTIVE: The present study focused on the development of a poloxamer 407 thermosensitive hydrogel loaded with keratinocyte growth factor-2 (KGF-2) and fibroblast growth factor-21 (FGF-21) as a therapeutic biomaterial in a scald-wound model of type-2 diabetes in Goto-Kakizaki (GK) rats. RESEARCH DESIGN AND METHODS: In this study, a poloxamer 407 thermosensitive hydrogel loaded with KGF-2 and/or FGF-21 was prepared and its physical and biological properties were characterized. The repairing effects of this hydrogel were investigated in a scald-wound model of type-2 diabetes in GK rats. The wound healing rate, epithelialization, and formation of granulation tissue were examined, and biomarkers reflecting regulation of proliferation and inflammation were quantified by immunostaining and Western blotting. T tests and analyses of variance were used for statistical analysis via Graphpad Prism V.6.0. RESULTS: A 17.0% (w/w) poloxamer 407 combined with 1.0% (w/w) glycerol exhibited controlled release characteristics and a three-dimensional structure. A KGF-2/FGF-21 poloxamer hydrogel promoted cellular migration without apoptosis. This KGF-2/FGF-21 poloxamer hydrogel also accelerated wound healing of scalded skin in GK rats better than that of a KGF-2 or FGF-21 hydrogel alone due to accelerated epithelialization, formation of granulation tissue, collagen synthesis, and angiogenesis via inhibition of inflammatory responses and increased expression of alpha-smooth muscle actin (α-SMA), collagen III, pan-keratin, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and CD31. CONCLUSIONS: A KGF-2/FGF-21 poloxamer hydrogel accelerated wound healing of scalded skin in GK rats, which was attributed to a synergistic effect of KGF-2-mediated cellular proliferation and FGF-21-mediated inhibition of inflammatory responses. Taken together, our findings provide a novel and potentially important insight into improving wound healing in patients with diabetic ulcers.
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spelling pubmed-72454512020-06-03 KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats Yang, Xuanxin Yang, Rongshuai Chen, Min Zhou, Qingde Zheng, Yingying Lu, Chao Bi, Jianing Sun, Wenzhe Huang, Tongzhou Li, Lijia Gong, Jianxiang Li, Xiaokun Hui, Qi Wang, Xiaojie BMJ Open Diabetes Res Care Emerging Technologies, Pharmacology and Therapeutics OBJECTIVE: The present study focused on the development of a poloxamer 407 thermosensitive hydrogel loaded with keratinocyte growth factor-2 (KGF-2) and fibroblast growth factor-21 (FGF-21) as a therapeutic biomaterial in a scald-wound model of type-2 diabetes in Goto-Kakizaki (GK) rats. RESEARCH DESIGN AND METHODS: In this study, a poloxamer 407 thermosensitive hydrogel loaded with KGF-2 and/or FGF-21 was prepared and its physical and biological properties were characterized. The repairing effects of this hydrogel were investigated in a scald-wound model of type-2 diabetes in GK rats. The wound healing rate, epithelialization, and formation of granulation tissue were examined, and biomarkers reflecting regulation of proliferation and inflammation were quantified by immunostaining and Western blotting. T tests and analyses of variance were used for statistical analysis via Graphpad Prism V.6.0. RESULTS: A 17.0% (w/w) poloxamer 407 combined with 1.0% (w/w) glycerol exhibited controlled release characteristics and a three-dimensional structure. A KGF-2/FGF-21 poloxamer hydrogel promoted cellular migration without apoptosis. This KGF-2/FGF-21 poloxamer hydrogel also accelerated wound healing of scalded skin in GK rats better than that of a KGF-2 or FGF-21 hydrogel alone due to accelerated epithelialization, formation of granulation tissue, collagen synthesis, and angiogenesis via inhibition of inflammatory responses and increased expression of alpha-smooth muscle actin (α-SMA), collagen III, pan-keratin, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and CD31. CONCLUSIONS: A KGF-2/FGF-21 poloxamer hydrogel accelerated wound healing of scalded skin in GK rats, which was attributed to a synergistic effect of KGF-2-mediated cellular proliferation and FGF-21-mediated inhibition of inflammatory responses. Taken together, our findings provide a novel and potentially important insight into improving wound healing in patients with diabetic ulcers. BMJ Publishing Group 2020-05-19 /pmc/articles/PMC7245451/ /pubmed/32434772 http://dx.doi.org/10.1136/bmjdrc-2019-001009 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Emerging Technologies, Pharmacology and Therapeutics
Yang, Xuanxin
Yang, Rongshuai
Chen, Min
Zhou, Qingde
Zheng, Yingying
Lu, Chao
Bi, Jianing
Sun, Wenzhe
Huang, Tongzhou
Li, Lijia
Gong, Jianxiang
Li, Xiaokun
Hui, Qi
Wang, Xiaojie
KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats
title KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats
title_full KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats
title_fullStr KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats
title_full_unstemmed KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats
title_short KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats
title_sort kgf-2 and fgf-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats
topic Emerging Technologies, Pharmacology and Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245451/
https://www.ncbi.nlm.nih.gov/pubmed/32434772
http://dx.doi.org/10.1136/bmjdrc-2019-001009
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