A thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells

Jixing Ye, Jing Wang, Yunxiao Zhu, Qiang Wei, Xin Wang, Jian Yang, Shengli Tang, Hao Liu, Jiaming Fan, Fugui Zhang, Evan M. Farina, Maryam K. Mohammed, Yulong Zou, Dongzhe Song, Junyi Liao, Jiayi Huang, Dan Guo, Minpeng Lu, Feng Liu, Jianxiang LiuLi Li, Chao Ma, Xue Hu, Rex C. Haydon, Michael J. Lee, Russell R. Reid, Guillermo A. Ameer, Li Yang, Tong Chuan He

Research output: Contribution to journalArticle

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Abstract

Successful bone tissue engineering requires at the minimum sufficient osteoblast progenitors, efficient osteoinductive factors, and biocompatible scaffolding materials. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Here, we investigated the potential use of a biodegradable citrate-based thermosensitive macromolecule, poly(polyethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN) mixed with gelatin (PPCNG) as a scaffold for the delivery of BMP9-stimulated MSCs to promote localized bone formation. The addition of gelatin to PPCN effectively enhanced the cell adhesion and survival properties of MSCs entrapped within the gel in 3D culture. Using the BMP9-transduced MSC line immortalized mouse embryonic fibroblasts (iMEFs), we found that PPCNG facilitated BMP9-induced osteogenic differentiation of iMEFs in vivo and promoted the formation of well-ossified and vascularized trabecular bone-like structures in a mouse model of ectopic bone formation. Histologic evaluation revealed that vascularization of the bony masses retrieved from the iMEFs + PPCNG group was significantly more pronounced than that of the direct cell injection group. Accordingly, vascular endothelial growth factor (VEGF) expression was shown to be significantly higher in the bony masses recovered from the iMEFs + PPCNG group. Taken together, our results suggest that PPCNG may serve as a novel biodegradable and injectable scaffold and carrier for gene and cell-based bone tissue engineering.

Original languageEnglish (US)
Article number025021
JournalBiomedical Materials (Bristol)
Volume11
Issue number2
DOIs
StatePublished - Apr 21 2016

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Growth Differentiation Factor 2
Gelatin
Stem cells
Scaffolds
Bone
Fibroblasts
Proteins
Citric Acid
Tissue engineering
Osteoblasts
Cell adhesion
Macromolecules
Cell culture
Vascular Endothelial Growth Factor A
Genes
Gels
Scaffolds (biology)

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Biomedical Engineering

Cite this

Ye, Jixing ; Wang, Jing ; Zhu, Yunxiao ; Wei, Qiang ; Wang, Xin ; Yang, Jian ; Tang, Shengli ; Liu, Hao ; Fan, Jiaming ; Zhang, Fugui ; Farina, Evan M. ; Mohammed, Maryam K. ; Zou, Yulong ; Song, Dongzhe ; Liao, Junyi ; Huang, Jiayi ; Guo, Dan ; Lu, Minpeng ; Liu, Feng ; Liu, Jianxiang ; Li, Li ; Ma, Chao ; Hu, Xue ; Haydon, Rex C. ; Lee, Michael J. ; Reid, Russell R. ; Ameer, Guillermo A. ; Yang, Li ; He, Tong Chuan. / A thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells. In: Biomedical Materials (Bristol). 2016 ; Vol. 11, No. 2.
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title = "A thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells",
abstract = "Successful bone tissue engineering requires at the minimum sufficient osteoblast progenitors, efficient osteoinductive factors, and biocompatible scaffolding materials. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Here, we investigated the potential use of a biodegradable citrate-based thermosensitive macromolecule, poly(polyethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN) mixed with gelatin (PPCNG) as a scaffold for the delivery of BMP9-stimulated MSCs to promote localized bone formation. The addition of gelatin to PPCN effectively enhanced the cell adhesion and survival properties of MSCs entrapped within the gel in 3D culture. Using the BMP9-transduced MSC line immortalized mouse embryonic fibroblasts (iMEFs), we found that PPCNG facilitated BMP9-induced osteogenic differentiation of iMEFs in vivo and promoted the formation of well-ossified and vascularized trabecular bone-like structures in a mouse model of ectopic bone formation. Histologic evaluation revealed that vascularization of the bony masses retrieved from the iMEFs + PPCNG group was significantly more pronounced than that of the direct cell injection group. Accordingly, vascular endothelial growth factor (VEGF) expression was shown to be significantly higher in the bony masses recovered from the iMEFs + PPCNG group. Taken together, our results suggest that PPCNG may serve as a novel biodegradable and injectable scaffold and carrier for gene and cell-based bone tissue engineering.",
author = "Jixing Ye and Jing Wang and Yunxiao Zhu and Qiang Wei and Xin Wang and Jian Yang and Shengli Tang and Hao Liu and Jiaming Fan and Fugui Zhang and Farina, {Evan M.} and Mohammed, {Maryam K.} and Yulong Zou and Dongzhe Song and Junyi Liao and Jiayi Huang and Dan Guo and Minpeng Lu and Feng Liu and Jianxiang Liu and Li Li and Chao Ma and Xue Hu and Haydon, {Rex C.} and Lee, {Michael J.} and Reid, {Russell R.} and Ameer, {Guillermo A.} and Li Yang and He, {Tong Chuan}",
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language = "English (US)",
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Ye, J, Wang, J, Zhu, Y, Wei, Q, Wang, X, Yang, J, Tang, S, Liu, H, Fan, J, Zhang, F, Farina, EM, Mohammed, MK, Zou, Y, Song, D, Liao, J, Huang, J, Guo, D, Lu, M, Liu, F, Liu, J, Li, L, Ma, C, Hu, X, Haydon, RC, Lee, MJ, Reid, RR, Ameer, GA, Yang, L & He, TC 2016, 'A thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells', Biomedical Materials (Bristol), vol. 11, no. 2, 025021. https://doi.org/10.1088/1748-6041/11/2/025021

A thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells. / Ye, Jixing; Wang, Jing; Zhu, Yunxiao; Wei, Qiang; Wang, Xin; Yang, Jian; Tang, Shengli; Liu, Hao; Fan, Jiaming; Zhang, Fugui; Farina, Evan M.; Mohammed, Maryam K.; Zou, Yulong; Song, Dongzhe; Liao, Junyi; Huang, Jiayi; Guo, Dan; Lu, Minpeng; Liu, Feng; Liu, Jianxiang; Li, Li; Ma, Chao; Hu, Xue; Haydon, Rex C.; Lee, Michael J.; Reid, Russell R.; Ameer, Guillermo A.; Yang, Li; He, Tong Chuan.

In: Biomedical Materials (Bristol), Vol. 11, No. 2, 025021, 21.04.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells

AU - Ye, Jixing

AU - Wang, Jing

AU - Zhu, Yunxiao

AU - Wei, Qiang

AU - Wang, Xin

AU - Yang, Jian

AU - Tang, Shengli

AU - Liu, Hao

AU - Fan, Jiaming

AU - Zhang, Fugui

AU - Farina, Evan M.

AU - Mohammed, Maryam K.

AU - Zou, Yulong

AU - Song, Dongzhe

AU - Liao, Junyi

AU - Huang, Jiayi

AU - Guo, Dan

AU - Lu, Minpeng

AU - Liu, Feng

AU - Liu, Jianxiang

AU - Li, Li

AU - Ma, Chao

AU - Hu, Xue

AU - Haydon, Rex C.

AU - Lee, Michael J.

AU - Reid, Russell R.

AU - Ameer, Guillermo A.

AU - Yang, Li

AU - He, Tong Chuan

PY - 2016/4/21

Y1 - 2016/4/21

N2 - Successful bone tissue engineering requires at the minimum sufficient osteoblast progenitors, efficient osteoinductive factors, and biocompatible scaffolding materials. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Here, we investigated the potential use of a biodegradable citrate-based thermosensitive macromolecule, poly(polyethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN) mixed with gelatin (PPCNG) as a scaffold for the delivery of BMP9-stimulated MSCs to promote localized bone formation. The addition of gelatin to PPCN effectively enhanced the cell adhesion and survival properties of MSCs entrapped within the gel in 3D culture. Using the BMP9-transduced MSC line immortalized mouse embryonic fibroblasts (iMEFs), we found that PPCNG facilitated BMP9-induced osteogenic differentiation of iMEFs in vivo and promoted the formation of well-ossified and vascularized trabecular bone-like structures in a mouse model of ectopic bone formation. Histologic evaluation revealed that vascularization of the bony masses retrieved from the iMEFs + PPCNG group was significantly more pronounced than that of the direct cell injection group. Accordingly, vascular endothelial growth factor (VEGF) expression was shown to be significantly higher in the bony masses recovered from the iMEFs + PPCNG group. Taken together, our results suggest that PPCNG may serve as a novel biodegradable and injectable scaffold and carrier for gene and cell-based bone tissue engineering.

AB - Successful bone tissue engineering requires at the minimum sufficient osteoblast progenitors, efficient osteoinductive factors, and biocompatible scaffolding materials. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Here, we investigated the potential use of a biodegradable citrate-based thermosensitive macromolecule, poly(polyethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN) mixed with gelatin (PPCNG) as a scaffold for the delivery of BMP9-stimulated MSCs to promote localized bone formation. The addition of gelatin to PPCN effectively enhanced the cell adhesion and survival properties of MSCs entrapped within the gel in 3D culture. Using the BMP9-transduced MSC line immortalized mouse embryonic fibroblasts (iMEFs), we found that PPCNG facilitated BMP9-induced osteogenic differentiation of iMEFs in vivo and promoted the formation of well-ossified and vascularized trabecular bone-like structures in a mouse model of ectopic bone formation. Histologic evaluation revealed that vascularization of the bony masses retrieved from the iMEFs + PPCNG group was significantly more pronounced than that of the direct cell injection group. Accordingly, vascular endothelial growth factor (VEGF) expression was shown to be significantly higher in the bony masses recovered from the iMEFs + PPCNG group. Taken together, our results suggest that PPCNG may serve as a novel biodegradable and injectable scaffold and carrier for gene and cell-based bone tissue engineering.

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