Light-triggered RNA release and induction of hMSC osteogenesis via photodegradable, dual-crosslinked hydrogels

Light-triggered RNA release and induction of hMSC osteogenesis via photodegradable, dual-crosslinked hydrogels
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DOI:
10.2217/nnm-2016-0088
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发表时间:
2016-06-01
期刊:
影响因子:
5.5
通讯作者:
Alsberg, Eben
Alsberg, Eben
中科院分区:
医学3区
文献类型:
--
作者:
Cong Truc Huynh;Minh Khanh Nguyen;Alsberg, Eben

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目的:设计一种可光降解的水凝胶系统,在指定时间点主动控制释放生物活性未修饰的RNA,以诱导hMSC成骨。材料和方法:将RNA/聚乙烯亚胺复合物装载到双重交联的光可降解水凝胶中,以检查紫外光应用触发其释放的能力。还研究了释放的RNA驱动hMSC成骨分化的能力。结果与结论:RNA从光降解水凝胶中的释放在UV应用时加速,这在非光降解水凝胶中没有观察到。无论是否存在UV光,释放的siGFP通过在HeLa细胞中沉默GFP表达而表现出高生物活性。重要的是,从水凝胶释放的siNoggin或miRNA-20 a诱导hMSC成骨。该系统为生物医学应用提供了一个潜在的有价值的医生/患者控制的“按需”RNA递送平台。
Aim: To engineer a photodegradable hydrogel system for actively controlled release of bioactive unmodified RNA at designated time points to induce hMSC osteogenesis. Materials & methods: RNA/polyethylenimine complexes were loaded into dual-crosslinked photodegradable hydrogels to examine the capacity of UV light application to trigger their release. The ability of released RNA to drive hMSC osteogenic differentiation was also investigated. Results & conclusion: RNA release from photodegradable hydrogels was accelerated upon UV application, which was not observed in non-photodegradable hydrogels. Regardless of the presence of UV light, released siGFP exhibited high bioactivity by silencing GFP expression in HeLa cells. Importantly, siNoggin or miRNA-20a released from the hydrogels induced hMSC osteogenesis. This system provides a potentially valuable physician/patient-controlled 'on-demand' RNA delivery platform for biomedical applications.