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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2020
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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. |
format | Online Article Text |
id | pubmed-7245451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
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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