A thermoresponsive 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 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.
Department of Biomedical Engineering, School of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China. Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
Jixing
J
Ye
Jing
J
Wang
Yunxiao
Y
Zhu
Qiang
Q
Wei
Xin
X
Wang
Jian
J
Yang
Shengli
S
Tang
Hao
H
Liu
Jiaming
J
Fan
Fugui
F
Zhang
Evan M
EM
Farina
Maryam K
MK
Mohammed
Yulong
Y
Zou
Dongzhe
D
Song
Junyi
J
Liao
Jiayi
J
Huang
Dan
D
Guo
Minpeng
M
Lu
Feng
F
Liu
Jianxiang
J
Liu
Li
L
Li
Chao
C
Ma
Xue
X
Hu
Rex C
RC
Haydon
Michael J
MJ
Lee
Russell R
RR
Reid
Guillermo A
GA
Ameer
Li
L
Yang
Tong-Chuan
TC
He
D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival; D002951:Citrates / Q000737:chemistry; D005260:Female; D005780:Gelatin / Q000737:chemistry; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000235:genetics / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D008422:Materials Testing; D008546:Melanoma, Experimental; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D010012:Osteogenesis / Q000502:physiology*; D011092:Polyethylene Glycols / Q000737:chemistry; D013696:Temperature; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D014161:Transduction, Genetic
D000180:Acrylic Resins; D001672:Biocompatible Materials; D002951:Citrates; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; C441456:poly(N-isopropyl acrylamide-co-ethyleneoxide); D011092:Polyethylene Glycols; D005780:Gelatin