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In situ bone tissue engineering using gene delivery nanocomplexes.
Acta Biomaterialia ( IF 9.7 ) Pub Date : 2020-03-08 , DOI: 10.1016/j.actbio.2020.03.008
Atefeh Malek-Khatabi 1 , Hamid Akbari Javar 1 , Erfan Dashtimoghadam 2 , Sahar Ansari 3 , Mohammad Mahdi Hasani-Sadrabadi 4 , Alireza Moshaverinia 4
Affiliation  

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(ε-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 SIGNIFICANCE: In 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.

中文翻译:

使用基因递送纳米复合物的原位骨组织工程。

基因传递为细胞和组织水平的丢失组织的功能恢复或再生提供了有希望的结果。但是,需要更有效的载体来安全和本地地运送遗传材料。在这里,我们演示了基于骨DNA再生的基于质粒DNA(pDNA)的纳米复合物(NC)平台的微流辅助合成。编码人骨形态发生蛋白2(BMP-2)的pDNA被用作目的基因。使用微混合器平台进行了pDNA和壳聚糖(CS)之间纳米复合物(NCs)的形成和微调。调节流动特性以调节混合时间,进而调节组装NC的尺寸,ζ电位和紧凑性。后来,将NC固定在用金属蛋白酶敏感肽(对MMP敏感)功能化的纳米纤维聚(ε-己内酯)(PCL)支架上。该构建体可以提供对环境敏感的和局部的基因递送平台。使用化学和生物学方法研究了骨髓源性间充质干细胞(MSCs)的成骨分化。呈现的结果汇聚在一起,表明使用固定化的微流体合成的基因递送纳米复合物开发的原位骨组织工程方法学的巨大潜力,该方法很容易在再生纳米医学领域扩展。重大意义声明:在这项研究中,我们证明了用于骨骼组织再生的基于质粒DNA(pDNA)的纳米复合物(NCs)平台的微流辅助合成。我们使用编码人骨形态发生蛋白2(BMP-2)的pDNA作为目标基因。使用micromixer平台,pDNA和壳聚糖(CS)之间的纳米复合物(NCs)得以制备和优化。将NC固定在用金属蛋白酶敏感肽功能化的纳米纤维聚己内酯支架上。体外和体内测定证实了间充质干细胞(MSC)的成骨分化。获得的数据表明,使用固定化的微流体合成的基因递送纳米复合物开发的原位骨组织工程方法学的巨大潜力,该方法很容易在再生纳米医学领域扩展。将NC固定在用金属蛋白酶敏感肽功能化的纳米纤维聚己内酯支架上。体外和体内测定证实了间充质干细胞(MSC)的成骨分化。获得的数据表明,使用固定化的微流体合成的基因递送纳米复合物开发的原位骨组织工程方法学的巨大潜力,该方法很容易在再生纳米医学领域扩展。将NC固定在用金属蛋白酶敏感肽功能化的纳米纤维聚己内酯支架上。体外和体内测定证实了间充质干细胞(MSC)的成骨分化。获得的数据表明,使用固定化的微流体合成的基因递送纳米复合物开发的原位骨组织工程方法学的巨大潜力,该方法很容易在再生纳米医学领域扩展。
更新日期:2020-03-08
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