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Athermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from bmp9-transduced mesenchymal stem cells

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 differ... Full description

Journal Title: Biomedical Materials 2016, Vol.11(2), p.025021 (13pp)
Main Author: Ye, Jixing
Other Authors: 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
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1748-6041 ; E-ISSN: 1748-605X ; DOI: 10.1088/1748-6041/11/2/025021
Link: http://dx.doi.org/10.1088/1748-6041/11/2/025021
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recordid: iop10.1088/1748-6041/11/2/025021
title: Athermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from bmp9-transduced mesenchymal stem cells
format: Article
creator:
  • 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
subjects:
  • Engineering
ispartof: Biomedical Materials, 2016, Vol.11(2), p.025021 (13pp)
description: 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.
language: eng
source:
identifier: ISSN: 1748-6041 ; E-ISSN: 1748-605X ; DOI: 10.1088/1748-6041/11/2/025021
fulltext: no_fulltext
issn:
  • 1748-6041
  • 1748-605X
  • 17486041
  • 1748605X
url: Link


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titleAthermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from bmp9-transduced mesenchymal stem cells
creatorYe, 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
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descriptionSuccessful 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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titleA thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells
descriptionSuccessful 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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atitleA thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells
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abstractSuccessful 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.
doi10.1088/1748-6041/11/2/025021
date2016-04-01