Sustained localized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation.

Sustained localized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation.
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DOI:
10.1016/j.biomaterials.2014.04.048
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发表时间:
2014-08
期刊:
影响因子:
14
通讯作者:
Alsberg, Eben
Alsberg, Eben
中科院分区:
工程技术1区
文献类型:
--
作者:
Nguyen, Minh K.;Jeon, Oju;Krebs, Melissa D.;Schapira, Daniel;Alsberg, Eben

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迄今为止,RNA干扰分子已被用于在不模拟体内三维(3D)微环境的二维(2D)基质上分化干细胞。在这里,原位形成的聚(乙二醇)(PEG)水凝胶被设计用于RNA干扰分子的受控,局部和持续递送,以分化封装在3D聚合物网络内的干细胞。RNA干扰分子在3-6周的过程中以持续和受控的方式从水凝胶中释放,并表现出高生物活性。重要的是,证明了从水凝胶构建体递送siRNA和/或miRNA增强了包封的干细胞的成骨分化。与体外进行的传统siRNA实验不同,siRNA和/或miRNA从该聚合物支架的延长递送允许延长细胞行为的调节。这种方法为控制细胞命运提供了一种强有力的新方法,并有望在组织工程和再生医学中获得多种应用。
To date, RNA interfering molecules have been used to differentiate stem cells on two-dimensional (2D) substrates that do not mimic three-dimensional (3D) microenvironments in the body. Here, in situ forming poly(ethylene glycol) (PEG) hydrogels were engineered for controlled, localized and sustained delivery of RNA interfering molecules to differentiate stem cells encapsulated within the 3D polymer network. RNA interfering molecules were released from the hydrogels in a sustained and controlled manner over the course of 3-6 weeks, and exhibited high bioactivity. Importantly, it was demonstrated that the delivery of siRNA and/or miRNA from the hydrogel constructs enhanced the osteogenic differentiation of encapsulated stem cells. Prolonged delivery of siRNA and/or miRNA from this polymeric scaffold permitted extended regulation of cell behavior, unlike traditional siRNA experiments performed in vitro. This approach presents a powerful new methodology for controlling cell fate, and is promising for multiple applications in tissue engineering and regenerative medicine.
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