In situ-forming collagen/poly-γ-glutamic acid hydrogel system with mesenchymal stem cells and bone morphogenetic protein-2 for bone tissue regeneration in a mouse calvarial bone defect model

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Title
In situ-forming collagen/poly-γ-glutamic acid hydrogel system with mesenchymal stem cells and bone morphogenetic protein-2 for bone tissue regeneration in a mouse calvarial bone defect model
Author(s)
S H Cho; Keun Koo Shin; S Y Kim; M Y Cho; Doo-Byoung Oh; Y T Lim
Bibliographic Citation
Tissue Engineering and Regenerative Medicine, vol. 19, no. 5, pp. 1099-1111
Publication Year
2022
Abstract
Background: Bone marrow-derived mesenchymal stem cells (BMSCs) and bone morphogenetic protein-2 (BMP-2) have been studied for bone repair because they have regenerative potential to differentiate into osteoblasts. The development of injectable and in situ three-dimensional (3D) scaffolds to proliferate and differentiate BMSCs and deliver BMP-2 is a crucial technology in BMSC-based tissue engineering. Methods: The proliferation of mouse BMSCs (mBMSCs) in collagen/poly-γ-glutamic acid (Col/γ-PGA) hydrogel was evaluated using LIVE/DEAD and acridine orange and propidium iodide assays. In vitro osteogenic differentiation and the gene expression level of Col/γ-PGA(mBMSC/BMP-2) were assessed by alizarin red S staining and quantitative reverse-transcription polymerase chain reaction. The bone regeneration effect of Col/γ-PGA(mBMSC/BMP-2) was evaluated in a mouse calvarial bone defect model. The cranial bones of the mice were monitored by micro-computed tomography and histological analysis. Results: The developed Col/γ-PGA hydrogel showed low viscosity below ambient temperature, while it provided a high elastic modulus and viscous modulus at body temperature. After gelation, the Col/γ-PGA hydrogel showed a 3D and interconnected porous structure, which helped the effective proliferation of BMSCs with BMP-2. The Col/γ-PGA (mBMSC/BMP-2) expressed more osteogenic genes and showed effective orthotopic bone formation in a mouse model with a critical-sized bone defect in only 3-4 weeks. Conclusion: The Col/γ-PGA(mBMSC/BMP-2) hydrogel was suggested to be a promising platform by combining collagen as a major component of the extracellular matrix and γ-PGA as a viscosity reducer for easy handling at room temperature in BMSC-based bone tissue engineering scaffolds.
Keyword
Hydrogel scaffoldBone morphogenetic protein-2Mesenchymal stem cellCalvarial defectBone regeneration
ISSN
1738-2696
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.1007/s13770-022-00454-4
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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