In situ bone tissue engineering using gene delivery nanocomplexes
In situ bone tissue engineering using gene delivery nanocomplexes
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DOI：
10.1016/j.actbio.2020.03.008
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发表时间：
2020-05-01
影响因子：
9.7
通讯作者：
Moshaverinia, Alireza
中科院分区：
文献类型：
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作者：
Malek-Khatabi, Atefeh;Javar, Hamid Akbari;Moshaverinia, Alireza
基因递送在细胞和组织水平上为功能恢复或丢失组织的再生提供了有希望的结果。然而，需要更有效的载体来安全地和局部地递送遗传物质。在此，我们展示了用于骨组织再生的基于质粒DNA（pDNA）的纳米颗粒（NC）平台的微流体辅助合成。使用编码人骨形态发生蛋白-2（BMP-2）的pDNA作为目的基因。使用微混合器平台进行pDNA和作为载体的壳聚糖（CS）之间的纳米复合物（NC）的形成和微调。调节流动特性以调节混合时间，并因此调节组装的NC的尺寸、ζ电位和致密性。随后，将NC固定在用金属蛋白酶敏感肽（MMP-敏感的）官能化的纳米纤维聚（ε-己内酯）（PCL）支架上。该构建体可以提供环境敏感的和定位的基因递送平台。采用化学和生物学方法研究了骨髓间充质干细胞（MSCs）的成骨分化。所提出的结果收敛，以表明一个巨大的潜力的开发方法，用于原位骨组织工程使用固定的微流体合成的基因传递nanocomposes，这是很容易扩展的领域再生nanomedicine.Statement的意义在这项研究中，我们证明了微流体辅助合成的质粒DNA（pDNA）为基础的nanocomposes（NC）平台骨组织再生。我们使用编码人骨形态发生蛋白-2（BMP-2）的pDNA作为目的基因。利用微混合器平台制备并优化了pDNA与壳聚糖（CS）的纳米复合物（NC）。将NC固定在用金属蛋白酶敏感肽官能化的纳米纤维聚己内酯支架上。体外和体内实验证实了间充质干细胞（MSCs）的成骨分化。所获得的数据表明，使用固定化微流体合成的基因递送纳米复合物的原位骨组织工程的开发方法具有巨大的潜力，该方法在再生纳米医学领域易于扩展。(C)2020 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Gene delivery offers promising outcomes for functional recovery or regeneration of lost tissues at cellular and tissue levels. However, more efficient carriers are needed to safely and locally delivery of genetic materials. Herein, we demonstrate microfluidic-assisted synthesis of plasmid DNA (pDNA)-based nanocomplexe (NC) platforms for bone tissue regeneration. pDNA encoding human bone morphogenesis protein-2 (BMP-2) was used as a gene of interest. Formation and fine-tuning of nanocomplexes (NCs) between pDNA and chitosan (CS) as carriers were performed using a micromixer platform. Flow characteristics were adjusted to tune mixing time and consequently size, zeta potential, and compactness of assembled NCs. Subsequently, NCs were immobilized on a nanofibrous Poly(epsilon-caprolactone) (PCL) scaffold functionalized with metalloprotease-sensitive peptide (MMP-sensitive). This construct can provide an environmental-sensitive and localized gene delivery platform. Osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs) was studied using chemical and biological assays. The presented results converge to indicate a great potential of the developed methodology for in situ bone tissue engineering using immobilized microfluidic-synthesized gene delivery nanocomplexes, which is readily expandable in the field of regenerative nanomedicine.Statement of significanceIn this study, we demonstrate microfluidic-assisted synthesis of plasmid DNA (pDNA)-based nanocomplexes (NCs) platforms for bone tissue regeneration. We used pDNA encoding human bone morphogenesis protein-2 (BMP-2) as the gene of interest. Using micromixer platform nanocomplexes (NCs) between pDNA and chitosan (CS) were fabricated and optimized. NCs were immobilized on a nanofibrous polycaprolactone scaffold functionalized with metalloprotease-sensitive peptide. In vitro and in vivo assays confirmed the osteogenic differentiation of mesenchymal stem cells (MSCs). The obtained data indicated great potential of the developed methodology for in situ bone tissue engineering using immobilized microfluidic-synthesized gene delivery nanocomplexes, which is readily expandable in the field of regenerative nanomedicine. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.