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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...

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Autores principales: Lan, Biyun, Zhang, Liming, Yang, Liqun, Wu, Junfeng, Li, Na, Pan, Chenglin, Wang, Xiaoyi, Zeng, Lexiang, Yan, Li, Yang, Chuan, Ren, Meng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
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.
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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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