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Incorporation of osteogenic and angiogenic small interfering RNAs into chitosan sponge for bone tissue engineering
Engineered bone substitutes are being extensively explored in response to growing demand. However, the angiogenesis that occurs during bone formation is often overlooked in scaffold design. In this novel study, we incorporated two small interfering RNAs (siRNAs), ie, small interfering RNA targets ca...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242407/ https://www.ncbi.nlm.nih.gov/pubmed/25429217 http://dx.doi.org/10.2147/IJN.S70457 |
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author | Jia, Sen Yang, Xinjie Song, Wen Wang, Lei Fang, Kaixiu Hu, Zhiqiang Yang, Zihui Shan, Chun Lei, Delin Lu, Bin |
author_facet | Jia, Sen Yang, Xinjie Song, Wen Wang, Lei Fang, Kaixiu Hu, Zhiqiang Yang, Zihui Shan, Chun Lei, Delin Lu, Bin |
author_sort | Jia, Sen |
collection | PubMed |
description | Engineered bone substitutes are being extensively explored in response to growing demand. However, the angiogenesis that occurs during bone formation is often overlooked in scaffold design. In this novel study, we incorporated two small interfering RNAs (siRNAs), ie, small interfering RNA targets casein kinase 2 interaction protein 1 (siCkip-1) and small interfering RNA targets soluble VEGF receptor 1 (siFlt-1), which can promote osteogenesis and angiogenesis, into a chitosan sponge. This scaffold could maintain siRNAs for over 2 weeks in neutral phosphate-buffered saline and degraded rapidly in the presence of lysozyme. The chitosan sponge with siCkip-1 and siFlt-1 in vitro bioactivity was investigated using mesenchymal stem cells. Target genes were significantly suppressed, and osteocalcin, alkaline phosphatase, and vascular endothelial growth factor were significantly upregulated. Alizarin Red staining revealed that mineralization of the extracellular matrix was markedly enhanced by dual transfection. Further analysis by immunofluorescence confirmed that the siRNA-modified scaffold simultaneously improved the expression of osteocalcin and von Willebrand factor. In vivo testing in a skull critical-size defect model showed marked bone regeneration in rats treated with siCkip-1 and siFlt-1. In conclusion, chitosan sponge containing osteogenic and angiogenic siRNAs may be used as a scaffold for bone regeneration. The dual siRNA concept may also be useful in the biofunctionalization of other materials. |
format | Online Article Text |
id | pubmed-4242407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-42424072014-11-26 Incorporation of osteogenic and angiogenic small interfering RNAs into chitosan sponge for bone tissue engineering Jia, Sen Yang, Xinjie Song, Wen Wang, Lei Fang, Kaixiu Hu, Zhiqiang Yang, Zihui Shan, Chun Lei, Delin Lu, Bin Int J Nanomedicine Original Research Engineered bone substitutes are being extensively explored in response to growing demand. However, the angiogenesis that occurs during bone formation is often overlooked in scaffold design. In this novel study, we incorporated two small interfering RNAs (siRNAs), ie, small interfering RNA targets casein kinase 2 interaction protein 1 (siCkip-1) and small interfering RNA targets soluble VEGF receptor 1 (siFlt-1), which can promote osteogenesis and angiogenesis, into a chitosan sponge. This scaffold could maintain siRNAs for over 2 weeks in neutral phosphate-buffered saline and degraded rapidly in the presence of lysozyme. The chitosan sponge with siCkip-1 and siFlt-1 in vitro bioactivity was investigated using mesenchymal stem cells. Target genes were significantly suppressed, and osteocalcin, alkaline phosphatase, and vascular endothelial growth factor were significantly upregulated. Alizarin Red staining revealed that mineralization of the extracellular matrix was markedly enhanced by dual transfection. Further analysis by immunofluorescence confirmed that the siRNA-modified scaffold simultaneously improved the expression of osteocalcin and von Willebrand factor. In vivo testing in a skull critical-size defect model showed marked bone regeneration in rats treated with siCkip-1 and siFlt-1. In conclusion, chitosan sponge containing osteogenic and angiogenic siRNAs may be used as a scaffold for bone regeneration. The dual siRNA concept may also be useful in the biofunctionalization of other materials. Dove Medical Press 2014-11-17 /pmc/articles/PMC4242407/ /pubmed/25429217 http://dx.doi.org/10.2147/IJN.S70457 Text en © 2014 Jia et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Jia, Sen Yang, Xinjie Song, Wen Wang, Lei Fang, Kaixiu Hu, Zhiqiang Yang, Zihui Shan, Chun Lei, Delin Lu, Bin Incorporation of osteogenic and angiogenic small interfering RNAs into chitosan sponge for bone tissue engineering |
title | Incorporation of osteogenic and angiogenic small interfering RNAs into chitosan sponge for bone tissue engineering |
title_full | Incorporation of osteogenic and angiogenic small interfering RNAs into chitosan sponge for bone tissue engineering |
title_fullStr | Incorporation of osteogenic and angiogenic small interfering RNAs into chitosan sponge for bone tissue engineering |
title_full_unstemmed | Incorporation of osteogenic and angiogenic small interfering RNAs into chitosan sponge for bone tissue engineering |
title_short | Incorporation of osteogenic and angiogenic small interfering RNAs into chitosan sponge for bone tissue engineering |
title_sort | incorporation of osteogenic and angiogenic small interfering rnas into chitosan sponge for bone tissue engineering |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242407/ https://www.ncbi.nlm.nih.gov/pubmed/25429217 http://dx.doi.org/10.2147/IJN.S70457 |
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