A novel Lipidoid-MicroRNA formulation promotes calvarial bone regeneration.
A novel Lipidoid-MicroRNA formulation promotes calvarial bone regeneration.
复制标题
DOI：
10.1016/j.biomaterials.2018.05.038
复制
发表时间：
2018-09
期刊：
影响因子：
14
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Sui L;Wang M;Han Q;Yu L;Zhang L;Zheng L;Lian J;Zhang J;Valverde P;Xu Q;Tu Q;Chen J
特定的microRNAs（miRs）和Wnt信号通路在调节骨发育和稳态中起关键作用。我们先前的研究揭示了miR-335- 5 p通过下调Wnt拮抗剂Dickkopf-1（DKK 1）促进成骨分化的能力。本研究的目的是使用纳米材料有效地将miR-335- 5 p递送到成骨细胞中用于组织工程应用。我们合成并筛选了12个候选纳米类胡萝卜素的文库，其中L 8被鉴定为用于miRNA分子递送到细胞中的优选生物可降解类胡萝卜素。然后，我们研究了miR-335-5-p（LMF-335）的类胡萝卜素-miRNA制剂是否可以成功地将miR-335-5-p递送到细胞中以促进体外骨生成和体内颅骨愈合。LMF-335转染C3 H10 T1/2细胞和骨髓基质细胞（BMSCs）后，DKK 1表达降低，成骨关键基因表达增加。然后将LMF-335和LMF-335转染的BMSC与丝绸支架组合使用，以评估小鼠关键尺寸颅骨缺损的愈合情况。结果显示，与对照组相比，LMF-335组的缺损处有显著的新骨形成。总之，这第一份报告支持了这样的观点，即小RNA的类黄酮递送可用于诱导干细胞的成骨分化和骨再生。
Specific microRNAs (miRs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous studies revealed the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to use nano-materials to efficiently deliver miR-335-5p into osteogenic cells for tissue engineering applications. We synthesized and screened a library of 12 candidate nano-lipidoids, of which L8 was identified as the preferred biodegradable lipidoid for miRNA molecule delivery into cells. We then investigated whether a lipidoid-miRNA formulation of miR-335-5-p (LMF-335) could successfully deliver miR-335-5-p into cells to promote osteogenesis in vitro and calvarial bone healing in vivo. Transfection of C3H10T1/2 cells and bone marrow stromal cells (BMSCs) with LMF-335 led to decreased expression of DKK1 and increased expression of the key osteogenic genes. LMF-335 and LMF-335-transfected BMSCs were then used in combination with silk scaffolds to evaluate healing of critical-size calvarial bone defects in mice. The results revealed significant new bone formation in the defects in LMF-335 groups as compared with control groups. In conclusion, this first report supports the notion that lipidoid delivery of miRNA can be used to induce osteogenic differentiation of stem cells and bone regeneration.
登录
查看更多内容
影响因子：
12.4
作者：
Whitehead, Kathryn A.;Sahay, Gaurav;Anderson, Daniel G.
通讯作者：
Anderson, Daniel G.
影响因子：
4.7
作者：
Sun, Shuo;Wang, Ming;Knupp, Sarah A.;Soto-Feliciano, Yadira;Hu, Xiao;Kaplan, David L.;Langer, Robert;Anderson, Daniel G.;Xu, Qiaobing
通讯作者：
Xu, Qiaobing
影响因子：
12.4
作者：
Akinc, Akin;Goldberg, Michael;Anderson, Daniel G.
通讯作者：
Anderson, Daniel G.
影响因子：
6.2
作者：
Valverde, Paloma;Zhang, Jin;Chen, Jake
通讯作者：
Chen, Jake
影响因子：
56.9
作者：
LANGER, R;VACANTI, JP
通讯作者：
VACANTI, JP