Polysaccharide-modified scaffolds for controlled lentivirus delivery in vitro and after spinal cord injury

JOURNAL OF CONTROLLED RELEASE

卷:170

Article

Thomas, Aline M.¹  Shea, Lonnie D.^2,3,4,5,6 

[1] Northwestern Univ, Dept Biomed Engn, McCormick Sch Engn, Evanston, IL 60208 USA

[2] Northwestern Univ, Dept Chem & Biol Engn, McCormick Sch Engn, Evanston, IL 60208 USA

[3] Northwestern Univ, Inst BioNanotechnol Med IBNAM, Chicago, IL 60611 USA

[4] Northwestern Univ, Ctr Reprod Sci CRS, Evanston, IL 60208 USA

[5] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

[6] Northwestern Univ, Chem Life Proc Inst CLP, Evanston, IL 60208 USA

关键词: Gene delivery;    Lentivirus;    Polysaccharide;    Scaffold;    Multiple channel bridge;    Spinal cord injury;   

DOI  :  10.1016/j.jconrel.2013.06.013

来源: Elsevier

【 摘 要 】

Gene delivering biomaterials have increasingly been employed to modulate the cellular microenvironment to promote tissue regeneration, yet low transduction efficiency has been a persistent challenge for in vivo applications. In this report, we investigated the surface modification of poly(lactide-co-glycolide) (PLG) scaffolds with polysaccharides, which have been implicated in binding lentivirus but have not been used for delivery. Chitosan was directly conjugated onto PLG scaffolds, whereas heparin and hyaluronan were indirectly conjugated onto PLG scaffolds with multi-amine crosslinkers. The addition of chitosan and heparin onto PLG promoted the association of lentivirus to these scaffolds and enhanced their transduction efficiency in vitro relative to hyaluronan-conjugated and control scaffolds that had limited lentivirus association and transduction. Transduction efficiency in vitro was increased partly due to an enhanced retention of virus on the scaffold as well as an extended half-life of viral activity. Transduction efficiency was also evaluated in vivo using porous, multiple channel PLG bridges that delivered lentivirus to the injured mouse spinal cord. Transgene expression persisted for weeks after implantation, and was able to enhance axon growth and myelination. These studies support gene-delivering PLG scaffolds for in vivo regenerative medicine applications. (C) 2013 Elsevier B. V. All rights reserved.

【 授权许可】

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