Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects.
Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects.
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DOI：
10.1038/ncomms10376
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发表时间：
2016-01-14
影响因子：
16.6
通讯作者：
Ma PX
中科院分区：
文献类型：
--
作者：
Zhang X;Li Y;Chen YE;Chen J;Ma PX
MicroRNAs（miRNAs）被开发用于增强组织再生。在这里，我们表明，具有高的miRNA结合亲和力和可忽略的细胞毒性的超支化聚合物可以自组装成纳米级的聚合物与“双壳”的miRNA分布和高转染效率。这些复合物被封装在可生物降解的微球中，以实现可控的两阶段（复合物和miRNA）递送。微球附着在无细胞纳米纤维聚合物支架上，在空间上控制miR-26 a的释放。该技术通过靶向Gsk-3β激活内源性干细胞的成骨活性，用于再生骨质疏松小鼠的临界尺寸骨缺损，从而解决了再生医学中实现无细胞支架miRNA治疗组织工程的关键挑战。 再生医学的一个挑战是开发无细胞、非免疫原性的miRNA递送支架。在这里，作者设计了一种无细胞支架，能够有效和延长miRNA-26 a向内源性细胞的递送，并表明它可以在小鼠中再生全层颅骨缺损。
MicroRNAs (miRNAs) are being developed to enhance tissue regeneration. Here we show that a hyperbranched polymer with high miRNA-binding affinity and negligible cytotoxicity can self-assemble into nano-sized polyplexes with a ‘double-shell' miRNA distribution and high transfection efficiency. These polyplexes are encapsulated in biodegradable microspheres to enable controllable two-stage (polyplexes and miRNA) delivery. The microspheres are attached to cell-free nanofibrous polymer scaffolds that spatially control the release of miR-26a. This technology is used to regenerate critical-sized bone defects in osteoporotic mice by targeting Gsk-3β to activate the osteoblastic activity of endogenous stem cells, thus addressing a critical challenge in regenerative medicine of achieving cell-free scaffold-based miRNA therapy for tissue engineering. A challenge in regenerative medicine is the development of cell-free, non-immunogenic miRNA-delivering scaffolds. Here the authors design a cell-free scaffold capable of efficient and prolonged delivery of miRNA-26a to endogenous cells and show that it can regenerate a full-thickness calvarial bone defect in mice.