Development of a gene-activated scaffold platformfor tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds
Development of a gene-activated scaffold platformfor tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds
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DOI：
10.1016/j.jconrel.2015.05.005
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发表时间：
2015-07-28
影响因子：
10.8
通讯作者：
O'Brien, Fergal J.
中科院分区：
文献类型：
--
作者：
Raftery, Rosanne M.;Tierney, Erica G.;O'Brien, Fergal J.
支持细胞渗透和组织形成的生物材料支架也可以作为药物、蛋白质和基因等治疗药物的输送平台。由于大量重组蛋白的突然释放可能会导致不良反应，本研究的目的是探索本实验室开发的一系列胶原蛋白支架作为基因激活的支架平台在组织工程中的应用潜力。利用间充质干细胞(MSCs)对壳聚糖作为基因载体的潜力进行了研究。据报道，~gt；45%的转染率与非病毒金标准载体聚乙烯亚胺(PEI)的转染率相似，而不会引起细胞毒性副作用。将优化后的壳聚糖纳米颗粒加入到一系列胶原基支架中，种植在支架上的MSCs的转基因持续表达可维持长达28天，有趣的是，支架的组成对转基因效率有影响。这些结果表明，通过简单地改变支架组成和所选择的基因(或其组合)，该系统具有广泛的治疗应用的潜力。(C)2015爱思唯尔B.V.保留所有权利。
Biomaterial scaffolds that support cell infiltration and tissue formation can also function as platforms for the delivery of therapeutics such as drugs, proteins, and genes. As burst release of supraphysiological quantities of recombinant proteins can result in adverse side effects, the objective of this study was to explore the potential of a series of collagen-based scaffolds, developed in our laboratory, as gene-activated scaffold platforms with potential in a range of tissue engineering applications. The potential of chitosan, a biocompatible material derived from the shells of crustaceans, as a gene delivery vector was assessed using mesenchymal stem cells (MSCs). A transfection efficiency of >45% is reported which is similar to what is achieved with polyethyleneimine (PEI), a non-viral gold standard vector, without causing cytotoxic side effects. When the optimised chitosan nanoparticles were incorporated into a series of collagen-based scaffolds, sustained transgene expression from MSCs seeded on the scaffolds was maintained for up to 28 days and interestingly the composition of the scaffold had an effect on transfection efficiency. These results demonstrate that by simply varying the scaffold composition and the gene (or combinations thereof) chosen; the systemhas potential for amyriad of therapeutic applications. (C) 2015 Elsevier B.V. All rights reserved.