BMP2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells

Abstract This is the first report on the development of a covalently bone morphogenetic protein-2 (BMP2)-immobilized hydrogel that is suitable for osteogenic differentiation of human periodontal ligament stem cells (hPLSCs). O-propargyl-tyrosine (OpgY) was site-specifically incorporated into BMP2 to...

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Autores principales: Seung Hun Park, Jin Seon Kwon, Byeong Sung Lee, Ji Hoon Park, Bo Keun Lee, Jeong-Ho Yun, Bun Yeoul Lee, Jae Ho Kim, Byoung Hyun Min, Tae Hyeon Yoo, Moon Suk Kim
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/7202879d65c94092bdcc810a5e5f670c
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spelling oai:doaj.org-article:7202879d65c94092bdcc810a5e5f670c2021-12-02T16:06:56ZBMP2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells10.1038/s41598-017-06911-82045-2322https://doaj.org/article/7202879d65c94092bdcc810a5e5f670c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06911-8https://doaj.org/toc/2045-2322Abstract This is the first report on the development of a covalently bone morphogenetic protein-2 (BMP2)-immobilized hydrogel that is suitable for osteogenic differentiation of human periodontal ligament stem cells (hPLSCs). O-propargyl-tyrosine (OpgY) was site-specifically incorporated into BMP2 to prepare BMP2-OpgY with an alkyne group. The engineered BMP2-OpgY exhibited osteogenic characteristics after in vitro osteogenic differentiation of hPLSCs, indicating the osteogenic ability of BMP2-OpgY. A methoxy polyethylene glycol-(polycaprolactone-(N3)) block copolymer (MC-N3) was prepared as an injectable in situ-forming hydrogel. BMP2 covalently immobilized on an MC hydrogel (MC-BMP2) was prepared quantitatively by a simple biorthogonal reaction between alkyne groups on BMP2-OpgY and azide groups on MC-N3 via a Cu(I)-catalyzed click reaction. The hPLSCs-loaded MC-BMP2 formed a hydrogel almost immediately upon injection into animals. In vivo osteogenic differentiation of hPLSCs in the MC-BMP2 formulation was confirmed by histological staining and gene expression analyses. Histological staining of hPLSC-loaded MC-BMP2 implants showed evidence of mineralized calcium deposits, whereas hPLSC-loaded MC-Cl or BMP2-OpgY mixed with MC-Cl, implants showed no mineral deposits. Additionally, MC-BMP2 induced higher levels of osteogenic gene expression in hPLSCs than in other groups. In conclusion, BMP2-OpgY covalently immobilized on MC-BMP2 induced osteogenic differentiation of hPLSCs as a noninvasive method for bone tissue engineering.Seung Hun ParkJin Seon KwonByeong Sung LeeJi Hoon ParkBo Keun LeeJeong-Ho YunBun Yeoul LeeJae Ho KimByoung Hyun MinTae Hyeon YooMoon Suk KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Seung Hun Park
Jin Seon Kwon
Byeong Sung Lee
Ji Hoon Park
Bo Keun Lee
Jeong-Ho Yun
Bun Yeoul Lee
Jae Ho Kim
Byoung Hyun Min
Tae Hyeon Yoo
Moon Suk Kim
BMP2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells
description Abstract This is the first report on the development of a covalently bone morphogenetic protein-2 (BMP2)-immobilized hydrogel that is suitable for osteogenic differentiation of human periodontal ligament stem cells (hPLSCs). O-propargyl-tyrosine (OpgY) was site-specifically incorporated into BMP2 to prepare BMP2-OpgY with an alkyne group. The engineered BMP2-OpgY exhibited osteogenic characteristics after in vitro osteogenic differentiation of hPLSCs, indicating the osteogenic ability of BMP2-OpgY. A methoxy polyethylene glycol-(polycaprolactone-(N3)) block copolymer (MC-N3) was prepared as an injectable in situ-forming hydrogel. BMP2 covalently immobilized on an MC hydrogel (MC-BMP2) was prepared quantitatively by a simple biorthogonal reaction between alkyne groups on BMP2-OpgY and azide groups on MC-N3 via a Cu(I)-catalyzed click reaction. The hPLSCs-loaded MC-BMP2 formed a hydrogel almost immediately upon injection into animals. In vivo osteogenic differentiation of hPLSCs in the MC-BMP2 formulation was confirmed by histological staining and gene expression analyses. Histological staining of hPLSC-loaded MC-BMP2 implants showed evidence of mineralized calcium deposits, whereas hPLSC-loaded MC-Cl or BMP2-OpgY mixed with MC-Cl, implants showed no mineral deposits. Additionally, MC-BMP2 induced higher levels of osteogenic gene expression in hPLSCs than in other groups. In conclusion, BMP2-OpgY covalently immobilized on MC-BMP2 induced osteogenic differentiation of hPLSCs as a noninvasive method for bone tissue engineering.
format article
author Seung Hun Park
Jin Seon Kwon
Byeong Sung Lee
Ji Hoon Park
Bo Keun Lee
Jeong-Ho Yun
Bun Yeoul Lee
Jae Ho Kim
Byoung Hyun Min
Tae Hyeon Yoo
Moon Suk Kim
author_facet Seung Hun Park
Jin Seon Kwon
Byeong Sung Lee
Ji Hoon Park
Bo Keun Lee
Jeong-Ho Yun
Bun Yeoul Lee
Jae Ho Kim
Byoung Hyun Min
Tae Hyeon Yoo
Moon Suk Kim
author_sort Seung Hun Park
title BMP2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells
title_short BMP2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells
title_full BMP2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells
title_fullStr BMP2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells
title_full_unstemmed BMP2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells
title_sort bmp2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/7202879d65c94092bdcc810a5e5f670c
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