Scaffold-Free Spheroids with Two-Dimensional Heteronano-Layers (2DHNL) Enabling Stem Cell and Osteogenic Factor Codelivery for Bone Repair.

Scaffold-Free Spheroids with Two-Dimensional Heteronano-Layers (2DHNL) Enabling Stem Cell and Osteogenic Factor Codelivery for Bone Repair.
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具有二维异质纳米层(2DHNL)的无支架球体可实现干细胞和成骨因子的共同递送以用于骨修复

DOI:
10.1021/acsnano.1c09688
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发表时间:
2022-02-22
期刊:
影响因子:
17.1
通讯作者:
Lu, Lichun
Lu, Lichun
中科院分区:
材料科学1区
文献类型:
--
作者:
Liu, Xifeng;Li, Linli;Gaihre, Bipin;Park, Sungjo;Li, Yong;Terzic, Andre;Elder, Benjamin D.;Lu, Lichun

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无支架球体作为自下而上骨组织工程的直接细胞来源具有巨大的潜力。然而,构建具有细胞和生物活性信号的功能球体仍然具有挑战性。在这里,我们用间充质干细胞(MSC)和由黑磷(BP)和氧化石墨烯(GO)组成的二维异质纳米层(2DHNL)设计了功能性球体,以创建用于大缺损骨修复的3D细胞指导微环境。在体外三维球体微环境中评价工程化二维材料对干细胞增殖、成骨分化的影响。将这些工程化球体移植到临界大小的大鼠颅骨缺损中后,实现了对MSCs成骨、新血管形成和骨再生的良好体内支持。进一步加载成骨因子地塞米松(DEX)的2DHNL表现出突出的体内成骨诱导和骨再生,而无需在成骨培养基中进行体外培养。缩短的总培养时间将有利于临床翻译。这些浸渍有工程化2DHNL的功能性球状体能够实现干细胞和成骨因子的共递送,可能是有前途的功能性构建块,以在一体化系统中提供细胞和差异线索,从而产生用于时间有效的体内骨修复的大组织。
Scaffold-free spheroids offer great potential as a direct supply of cells for bottom-up bone tissue engineering. However, the building of functional spheroids with both cells and bioactive signals remains challenging. Here, we engineered functional spheroids with mesenchymal stem cells (MSCs) and two-dimensional hetero-nano-layers (2DHNL) that consisted of black phosphorus (BP) and graphene oxide (GO) to create a 3D cell-instructive microenvironment for large defect bone repair. The effects of the engineered 2D materials on the proliferation, osteogenic differentiation of stem cells was evaluated in an in vitro 3D spheroidal microenvironment. Excellent in vivo support of osteogenesis of MSCs, neovascularization, and bone regeneration was achieved after transplanting these engineered spheroids into critical-sized rat calvarial defects. Further loading of osteogenic factor dexamethasone (DEX) on the 2DHNL showed outstanding in vivo osteogenic induction and bone regrowth without prior in vitro culture in osteogenic medium. The shortened overall culture time would be advantageous for clinical translation. These functional spheroids impregnated with engineered 2DHNL enabling stem cell and osteogenic factor co-delivery could be promising functional building blocks to provide cells and differential clues in an all-in-one system to create large tissues for time-effective in vivo bone repair.
间充质干细胞:成骨细胞或脂肪细胞的细胞命运决定及其在骨质疏松症治疗中的应用
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