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通过基于明胶 - 胶原蛋白 - 聚乙二醇的电纺基质递送生物活性基因颗粒

Delivery of Bioactive Gene Particles via Gelatin-Collagen-PEG-Based Electrospun Matrices.

作者信息

Tsekoura Eleni K, Dick Teo, Pankongadisak Porntipa, Graf Daniel, Boluk Yaman, Uludağ Hasan

机构信息

Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada.

School of Science, Mae Fah Luang University, Thasud, Muang, Chiang Rai 57100, Thailand.

出版信息

Pharmaceuticals (Basel). 2021 Jul 12;14(7):666. doi: 10.3390/ph14070666.

Abstract

The fabrication of fiber mats via electrospinning has been adopted in the last decades to produce high quality scaffolds for tissue engineering. However, an effective combination of electrospinning methods with gene delivery therapies remains a challenge. In this study, we describe how the delivery of gene complexes via electrospun mats that contain different volumes of gelatin (Gel), collagen (Col), and polyethylene glycol (PEG) can affect gene expression by transfected cells. Non-viral complexes were formulated by using lipid modified polyethylenimine (PEI) polymer and plasmid DNAs (pDNA) like the reporter Green Fluorescent Protein (GFP) and the therapeutically relevant Bone Morphogenetic Protein-2 (BMP-2) and electrospuned after being mixed with different volumes of Gel-Col-PEG mats and delivered to human myoblast (C2C12) and mouse osteoblast cells (MC3T3). The entrapment of GFP complexes via different homogeneous electrospun fiber mats revealed that a high fraction of collagen in the mats affected the quality of the fibers and led to reduced transfection efficiency on target cells. On the other hand, the fabrication of double-layered mats that contained collagen without complexes as a first layer and gelatin-collagen-PEG with complexes as a second layer successfully induced GFP expression and ALP activity in C2C12 cells. We conclude that this study has established the advantage of formulating multilayered bioactive collagen-based mats for gene delivery applications.

摘要

在过去几十年中,通过静电纺丝制备纤维垫已被用于生产用于组织工程的高质量支架。然而,将静电纺丝方法与基因递送疗法有效结合仍然是一个挑战。在本研究中,我们描述了通过含有不同体积明胶(Gel)、胶原蛋白(Col)和聚乙二醇(PEG)的静电纺丝垫递送基因复合物如何影响转染细胞的基因表达。使用脂质修饰的聚乙烯亚胺(PEI)聚合物和质粒DNA(pDNA)(如报告基因绿色荧光蛋白(GFP)和具有治疗相关性的骨形态发生蛋白-2(BMP-2))制备非病毒复合物,并在与不同体积的Gel-Col-PEG垫混合后进行静电纺丝,然后递送至人成肌细胞(C2C12)和小鼠成骨细胞(MC3T3)。通过不同的均匀静电纺丝纤维垫包裹GFP复合物表明,垫中高比例的胶原蛋白会影响纤维质量,并导致对靶细胞的转染效率降低。另一方面,制备双层垫,第一层为不含复合物的胶原蛋白,第二层为含复合物的明胶-胶原蛋白-PEG,成功诱导了C2C12细胞中的GFP表达和碱性磷酸酶(ALP)活性。我们得出结论,本研究确立了制备用于基因递送应用的多层生物活性胶原基垫的优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23d5/8308744/8f9b2eb79367/pharmaceuticals-14-00666-g001a.jpg

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