방사선의학 웹진

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Abstract
This study developed a three-layer consecutive gene delivery system (T-CGDS) for timely gene delivery into human mesenchymal stem cells (hMSCs). The timing of transcription factor expression is important to effectively induce bone differentiation. Therefore, a three-layered nanocomposite was fabricated using differently sized gold nanoparticles to promote bone regeneration and osteogenic differentiation. The core layer comprised 80 nm gold nanoparticles coupled with ATF4 pDNA. Following coating with heparin-conjugated Pluronic F-127 (HP-F127), 50 nm gold nanoparticles coupled with SP7 pDNA were added to fabricate a bi-layer system. After further coating with HP-F127, 20 nm gold nanoparticles combined with RUNX2 pDNA were added. Consequently, a T-CGDS measuring 350-450 nm was fabricated. Genes were released for more than 8 days, while the size of the T-CGDS decreased over time. When the T-CGDS was applied to hMSCs, the gene in the outer layer (RUNX2) was expressed first, followed by those in the middle (SP7) and core (ATF4) layers. The T-CGDS effectively induced bone differentiation and regeneration in vitro and in vivo. Timely delivery of the ATF4 gene to stem cells via the T-CGDS can greatly assist osteogenic differentiation involved in bone regeneration.

Affiliations

Hye Jin Kim  1 , Sujin Lee  1 , Jong Min Park  1 , Hui Bang Cho  1 , Ji-In Park  1 , Ji Sun Park  2 , Keun-Hong Park  3
1 Laboratory of Nano-regenerative Medicine, Department of Biomedical Science, College of Life Science, CHA University, 6F, CHA Bio-Complex, 335 Pangyo-ro, Bundang-gu, Seongnam-si, 134-88, Republic of Korea.
2 Laboratory of Nano-regenerative Medicine, Department of Biomedical Science, College of Life Science, CHA University, 6F, CHA Bio-Complex, 335 Pangyo-ro, Bundang-gu, Seongnam-si, 134-88, Republic of Korea. Electronic address: pjs09@cha.ac.kr.
3 Laboratory of Nano-regenerative Medicine, Department of Biomedical Science, College of Life Science, CHA University, 6F, CHA Bio-Complex, 335 Pangyo-ro, Bundang-gu, Seongnam-si, 134-88, Republic of Korea. Electronic address: pkh0410@cha.ac.kr.