Tissue Engineering and Regenerative Medicine

  • Volume 19
  • /
  • Pages.1099-1111
  • /
  • 2022
  • /
  • 1738-2696(pISSN)
  • /
  • 2212-5469(eISSN)
Korean Tissue Engineering and Regenerative Medicine Society (한국조직공학·재생의학회)
권호 표지
DOI QR코드

DOI QR Code

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

  • Sun-Hee Cho (SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University) ;
  • Keun Koo Shin (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Sun-Young Kim (SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University) ;
  • Mi Young Cho (SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University) ;
  • Doo-Byoung Oh (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Yong Taik Lim (Department of Nano Engineering and School of Chemical Engineering, Sungkyunkwan University)
  • Received : 2021.10.26
  • Accepted : 2022.03.14
  • Published : 2022.04.23
⟨ Previous Next ⟩

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.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (Grant Nos. 2020R1A2C3006888, 2021R1C1C2003091), Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program, and an "R&D Convergence Program" of National Research Council of Science and Technology (NST) grant from the Korea government (MSIT) (Grant No. CAP-18-02-KRIBB).