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利用金纳米结构/肽纳米图案化氧化石墨烯增强脂肪间充质干细胞的成骨作用。

Enhancing osteogenesis of adipose-derived mesenchymal stem cells using gold nanostructure/peptide-nanopatterned graphene oxide.

机构信息

School of Integrative Engineering, Chung-Ang University, Seoul, Republic of Korea.

R&D Division, Nanobase, Inc., Seoul, Republic of Korea.

出版信息

Colloids Surf B Biointerfaces. 2021 Aug;204:111807. doi: 10.1016/j.colsurfb.2021.111807. Epub 2021 Apr 29.

DOI:10.1016/j.colsurfb.2021.111807
PMID:33964530
Abstract

Graphene derivatives are highly promising materials for use in stem-cell-based regenerative therapies, particularly for bone regeneration. Herein, we report a graphene oxide (GO)-based hybrid platform (GOHP) that is highly effective for guiding the osteogenesis of human adipose-derived mesenchymal stem cells (hAMSCs). A GO-coated indium tin oxide (ITO) substrate was electrochemically modified with Au nanostructures (GNSs), following which a cysteine-modified quadruple-branched arginine-glycine-aspartic acid was self-assembled on the ITO-GO-GNS hybrid via Au-S bonds. The synthesized GOHP, with the highest density of GNSs (deposition time of 120 s), exhibited the highest osteogenic differentiation efficiency based on the osteogenic marker expression level, osteocalcin expression, and osteoblastic mineralisation. Remarkably, although GO is known to be less efficient than the high-quality pure graphene synthesised via chemical vapour deposition (CVD), the fabricated GOHP exhibited an efficiency similar to that of CVD-grown graphene in guiding the osteogenesis of hAMSCs. The total RNA sequencing results revealed that CVD graphene and GOHP induced the osteogenesis of hAMSCs by upregulating the transcription factors related to direct osteogenesis, Wnt activation, and extracellular matrix deposition. Considering that GO is easy to produce, cost-effective, and biocompatible, the developed GOHP is highly promising for treating various diseases/disorders, including osteoporosis, rickets, and osteogenesis imperfecta.

摘要

石墨烯衍生物是用于基于干细胞的再生疗法的极具前景的材料,特别是在骨再生方面。在此,我们报告了一种基于氧化石墨烯(GO)的杂化平台(GOHP),该平台对于指导人脂肪间充质干细胞(hAMSCs)的成骨作用非常有效。GO 涂覆的氧化铟锡(ITO)基底通过 Au 纳米结构(GNS)进行电化学修饰,随后通过 Au-S 键将半胱氨酸修饰的四重分支精氨酸-甘氨酸-天冬氨酸自组装到 ITO-GO-GNS 杂化体上。所合成的 GOHP 具有最高密度的 GNS(沉积时间为 120 秒),基于成骨标志物表达水平、骨钙素表达和成骨细胞矿化,表现出最高的成骨分化效率。值得注意的是,尽管 GO 的效率已知低于通过化学气相沉积(CVD)合成的高质量纯石墨烯,但所制造的 GOHP 在指导 hAMSCs 成骨方面表现出与 CVD 生长的石墨烯相似的效率。总 RNA 测序结果表明,CVD 石墨烯和 GOHP 通过上调与直接成骨、Wnt 激活和细胞外基质沉积相关的转录因子来诱导 hAMSCs 的成骨作用。考虑到 GO 易于生产、具有成本效益且生物相容性好,所开发的 GOHP 非常有希望用于治疗各种疾病/障碍,包括骨质疏松症、佝偻病和成骨不全症。

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