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Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration

BACKGROUND: Regeneration of articular cartilage poses a tremendous challenge due to its limited self-repair capability and inflammation at the damaged site. To generate the desired structures that mimic the structure of native tissue, microtissues with repeated functional units such as cell aggregat...

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Autores principales: Asgari, Negin, Bagheri, Fatemeh, Eslaminejad, Mohamadreza Baghaban, Ghanian, Mohammad Hossein, Sayahpour, Forogh Azam, Ghafari, Amir Mohammad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367357/
https://www.ncbi.nlm.nih.gov/pubmed/32678019
http://dx.doi.org/10.1186/s13287-020-01797-2
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author Asgari, Negin
Bagheri, Fatemeh
Eslaminejad, Mohamadreza Baghaban
Ghanian, Mohammad Hossein
Sayahpour, Forogh Azam
Ghafari, Amir Mohammad
author_facet Asgari, Negin
Bagheri, Fatemeh
Eslaminejad, Mohamadreza Baghaban
Ghanian, Mohammad Hossein
Sayahpour, Forogh Azam
Ghafari, Amir Mohammad
author_sort Asgari, Negin
collection PubMed
description BACKGROUND: Regeneration of articular cartilage poses a tremendous challenge due to its limited self-repair capability and inflammation at the damaged site. To generate the desired structures that mimic the structure of native tissue, microtissues with repeated functional units such as cell aggregates have been developed. Multicellular aggregates of mesenchymal stem cells (MSCs) can be used as microscale building blocks of cartilage due to their potential for cell-cell contact, cell proliferation, and differentiation. METHODS: Chondrogenic microtissues were developed through incorporation of kartogenin-releasing poly (lactic-co-glycolic acid) (PLGA) microparticles (KGN-MP) within the MSC aggregates. The chondrogenic potential of KGN-MP treated MSC aggregates was proven in vitro by studying the chondrogenic markers at the RNA level and histological analysis. In order to address the inflammatory responses at the defect site, the microtissues were delivered in vivo via an injectable, anti-inflammatory hydrogel that contained gelatin methacryloyl (GelMA) loaded with curcumin (Cur). RESULTS: The KGN-MPs were fabricated to support MSCs during cartilage differentiation. According to real-time RT-PCR analysis, the presence of KGN in the aggregates led to the expression of cartilage markers by the MSCs. Both toluidine blue (TB) and safranin O (SO) staining demonstrated homogeneous glycosaminoglycan production throughout the KGN-MP incorporated MSC aggregates. The curcumin treatment efficiently reduced the expressions of hypertrophy markers by MSCs in vitro. The in vivo results showed that implantation of chondrogenic microtissues (KGN-MP incorporated MSC aggregates) using the curcumin loaded GelMA hydrogel resulted in cartilage tissue regeneration that had characteristic features close to the natural hyaline cartilage according to observational and histological results. CONCLUSIONS: The use of this novel construct that contained chondrogenic cell blocks and curcumin is highly desired for cartilage regeneration. GRAPHICAL ABSTRACT: [Image: see text]
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spelling pubmed-73673572020-07-20 Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration Asgari, Negin Bagheri, Fatemeh Eslaminejad, Mohamadreza Baghaban Ghanian, Mohammad Hossein Sayahpour, Forogh Azam Ghafari, Amir Mohammad Stem Cell Res Ther Research BACKGROUND: Regeneration of articular cartilage poses a tremendous challenge due to its limited self-repair capability and inflammation at the damaged site. To generate the desired structures that mimic the structure of native tissue, microtissues with repeated functional units such as cell aggregates have been developed. Multicellular aggregates of mesenchymal stem cells (MSCs) can be used as microscale building blocks of cartilage due to their potential for cell-cell contact, cell proliferation, and differentiation. METHODS: Chondrogenic microtissues were developed through incorporation of kartogenin-releasing poly (lactic-co-glycolic acid) (PLGA) microparticles (KGN-MP) within the MSC aggregates. The chondrogenic potential of KGN-MP treated MSC aggregates was proven in vitro by studying the chondrogenic markers at the RNA level and histological analysis. In order to address the inflammatory responses at the defect site, the microtissues were delivered in vivo via an injectable, anti-inflammatory hydrogel that contained gelatin methacryloyl (GelMA) loaded with curcumin (Cur). RESULTS: The KGN-MPs were fabricated to support MSCs during cartilage differentiation. According to real-time RT-PCR analysis, the presence of KGN in the aggregates led to the expression of cartilage markers by the MSCs. Both toluidine blue (TB) and safranin O (SO) staining demonstrated homogeneous glycosaminoglycan production throughout the KGN-MP incorporated MSC aggregates. The curcumin treatment efficiently reduced the expressions of hypertrophy markers by MSCs in vitro. The in vivo results showed that implantation of chondrogenic microtissues (KGN-MP incorporated MSC aggregates) using the curcumin loaded GelMA hydrogel resulted in cartilage tissue regeneration that had characteristic features close to the natural hyaline cartilage according to observational and histological results. CONCLUSIONS: The use of this novel construct that contained chondrogenic cell blocks and curcumin is highly desired for cartilage regeneration. GRAPHICAL ABSTRACT: [Image: see text] BioMed Central 2020-07-16 /pmc/articles/PMC7367357/ /pubmed/32678019 http://dx.doi.org/10.1186/s13287-020-01797-2 Text en © The Author(s) 2020 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/. The Creative Commons Public Domain Dedication waiver (http://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
Asgari, Negin
Bagheri, Fatemeh
Eslaminejad, Mohamadreza Baghaban
Ghanian, Mohammad Hossein
Sayahpour, Forogh Azam
Ghafari, Amir Mohammad
Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration
title Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration
title_full Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration
title_fullStr Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration
title_full_unstemmed Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration
title_short Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration
title_sort dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367357/
https://www.ncbi.nlm.nih.gov/pubmed/32678019
http://dx.doi.org/10.1186/s13287-020-01797-2
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