A PLG/HAp composite scaffold for lentivirus delivery

被引:38
作者
Boehler, R. M. [1 ]
Shin, S. [1 ]
Fast, A. G. [1 ]
Gower, R. M. [1 ]
Shea, L. D. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Northwestern Univ, Dept Chem & Biol Engn, Evanston, IL 60208 USA
[2] Northwestern Univ, Chem Life Proc Inst CLP, Evanston, IL 60208 USA
[3] Northwestern Univ, Inst BioNanotechnol Med IBNAM, Chicago, IL 60611 USA
[4] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA
[5] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
基金
美国国家卫生研究院;
关键词
Scaffold; Gene therapy; Lentivirus; Hydroxyapatite; TRANSGENE EXPRESSION; GENE-TRANSFER; IMMOBILIZATION; VECTOR; NANOPARTICLES;
D O I
10.1016/j.biomaterials.2013.04.009
中图分类号
R318 [生物医学工程];
学科分类号
100103 [病原生物学];
摘要
Gene delivery from tissue engineering scaffolds provides the opportunity to control the microenvironment by inducing expression of regenerative factors. Hydroxyapatite (HAp) nanoparticles can bind lentivirus, and we investigated the incorporation of HAP into poly(lactide-co-glycolide) (PLG) scaffolds in order to retain lentivirus added to the scaffold. PLG/HAp scaffolds loaded with lentivirus enhanced transgene expression over 10-fold in vitro relative to scaffolds without HAp. Following in vivo implantation, PLG/HAp scaffolds promoted transgene expression for more than 100 days, with the level and duration enhanced relative to control scaffolds with lentivirus/HAp complexes added to PLG scaffolds. The extent of HAp incorporated into the scaffold influenced transgene expression, in part through its impact on porous architecture. Expression in vivo was localized to PLG/HAp scaffolds, with macrophages the primary cell type transduced at day 3, yet transduction of neutrophils and dendritic cells was also observed. At day 21 in PLG/HAp scaffolds, non-immune cells were transduced to a greater extent than immune cells, a trend that was opposite results from PLG scaffolds. Thus, in addition to retaining the virus, PLG/HAp influenced cell infiltration and preferentially transduced non-immune cells. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5431 / 5438
页数:8
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