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Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing
Excessive expression of matrix metalloproteinase 9 (MMP-9) impedes healing of diabetic chronic wounds, thus wound dressing that could effectively inhibit the expression of MMP-9 offers significant clinical translation for diabetic wound healing. Herein, a hybrid hydrogel dressing was developed for l...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097905/ https://www.ncbi.nlm.nih.gov/pubmed/33952251 http://dx.doi.org/10.1186/s12951-021-00869-6 |
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author | Lan, Biyun Zhang, Liming Yang, Liqun Wu, Junfeng Li, Na Pan, Chenglin Wang, Xiaoyi Zeng, Lexiang Yan, Li Yang, Chuan Ren, Meng |
author_facet | Lan, Biyun Zhang, Liming Yang, Liqun Wu, Junfeng Li, Na Pan, Chenglin Wang, Xiaoyi Zeng, Lexiang Yan, Li Yang, Chuan Ren, Meng |
author_sort | Lan, Biyun |
collection | PubMed |
description | Excessive expression of matrix metalloproteinase 9 (MMP-9) impedes healing of diabetic chronic wounds, thus wound dressing that could effectively inhibit the expression of MMP-9 offers significant clinical translation for diabetic wound healing. Herein, a hybrid hydrogel dressing was developed for localized and sustained delivery of MMP-9 siRNA (siMMP-9). siMMP-9 was complexed with Gly-TETA (GT), the GT/siMMP9 complex was then loaded into a thermosensitive hydrogel based on Pluronic F-127 (PF) and methylcellulose (MC). In vitro, this hybrid hydrogel dressing exhibited negligible cytotoxicity, prolonged the release of GT/siMMP-9 for up to 7 days, and significantly reduced MMP-9 expression. In vivo assessment in diabetic rats demonstrated that hydrogel provided localized and sustained delivery via the thermosensitive controlled release of entrapped GT/siMMP-9 into wound tissues for 7 days, resulting in dramatic MMP-9 silencing which significantly improved diabetic wound closure. This hybrid hydrogel dressing exhibited excellent biocompatibility, with no observed systemic toxicity in rats. Taken together, the hybrid hydrogel dressing may constitute an effective and biocompatible means of enhancing diabetic wound healing through effective silencing of the MMP-9 gene, and this hydrogel delivery system also offers a platform for in vivo delivery of siRNA for the treatment of other diseases. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00869-6. |
format | Online Article Text |
id | pubmed-8097905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-80979052021-05-05 Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing Lan, Biyun Zhang, Liming Yang, Liqun Wu, Junfeng Li, Na Pan, Chenglin Wang, Xiaoyi Zeng, Lexiang Yan, Li Yang, Chuan Ren, Meng J Nanobiotechnology Research Excessive expression of matrix metalloproteinase 9 (MMP-9) impedes healing of diabetic chronic wounds, thus wound dressing that could effectively inhibit the expression of MMP-9 offers significant clinical translation for diabetic wound healing. Herein, a hybrid hydrogel dressing was developed for localized and sustained delivery of MMP-9 siRNA (siMMP-9). siMMP-9 was complexed with Gly-TETA (GT), the GT/siMMP9 complex was then loaded into a thermosensitive hydrogel based on Pluronic F-127 (PF) and methylcellulose (MC). In vitro, this hybrid hydrogel dressing exhibited negligible cytotoxicity, prolonged the release of GT/siMMP-9 for up to 7 days, and significantly reduced MMP-9 expression. In vivo assessment in diabetic rats demonstrated that hydrogel provided localized and sustained delivery via the thermosensitive controlled release of entrapped GT/siMMP-9 into wound tissues for 7 days, resulting in dramatic MMP-9 silencing which significantly improved diabetic wound closure. This hybrid hydrogel dressing exhibited excellent biocompatibility, with no observed systemic toxicity in rats. Taken together, the hybrid hydrogel dressing may constitute an effective and biocompatible means of enhancing diabetic wound healing through effective silencing of the MMP-9 gene, and this hydrogel delivery system also offers a platform for in vivo delivery of siRNA for the treatment of other diseases. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00869-6. BioMed Central 2021-05-05 /pmc/articles/PMC8097905/ /pubmed/33952251 http://dx.doi.org/10.1186/s12951-021-00869-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Lan, Biyun Zhang, Liming Yang, Liqun Wu, Junfeng Li, Na Pan, Chenglin Wang, Xiaoyi Zeng, Lexiang Yan, Li Yang, Chuan Ren, Meng Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing |
title | Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing |
title_full | Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing |
title_fullStr | Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing |
title_full_unstemmed | Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing |
title_short | Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing |
title_sort | sustained delivery of mmp-9 sirna via thermosensitive hydrogel accelerates diabetic wound healing |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097905/ https://www.ncbi.nlm.nih.gov/pubmed/33952251 http://dx.doi.org/10.1186/s12951-021-00869-6 |
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