Sustained transgene expression via citric acid-based polyester elastomers

Xue Qing Zhang, Huanghui Tang, Ryan Hoshi, Laura De Laporte, Hongjin Qiu, Xiaoyang Xu, Lonnie D. Shea, Guillermo Antonio Ameer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Polymeric scaffolds are an important tool in tissue engineering and gene delivery using porous scaffolds can be a viable approach to control tissue response. Herein we describe the use of a biodegradable polyester elastomer, poly(1,8-octanediol-co-citrate) (POC), as a substrate for plasmid immobilization and cellular transfection of colonizing cells. Plasmid (pDNA), either complexed with poly(ethyleneimine) (PEI) forming polyplexes or in its native state, was surface-immobilized onto POC scaffolds via adsorption. Polyplex-containing scaffolds showed higher loading and slower initial rates of release than naked pDNA-containing scaffolds. Seeding of HEK293 cells and porcine aortic smooth muscle cells (PASMC) onto polyplex loaded-scaffolds demonstrated cell proliferation and transfection in vitro up to 12 days, significantly longer relative to bolus transfection. In vivo, transfection was evaluated using the mouse intraperitoneal (IP) fat model. In contrast to the in vitro study, successful long-term transgene delivery was only achieved with the naked pDNA-containing scaffolds. In particular, naked pDNA-containing scaffolds promoted high levels of both luciferase and green fluorescent protein (GFP) expression in vivo for 2 weeks. The results demonstrate that POC scaffolds are a suitable material for substrate-mediated gene delivery. POC scaffolds can potentially support long-term biological cues to mediate tissue formation through non-viral gene delivery.

Original languageEnglish (US)
Pages (from-to)2632-2641
Number of pages10
JournalBiomaterials
Volume30
Issue number13
DOIs
StatePublished - May 1 2009

Keywords

  • Biodegradable polyesters
  • Poly(diol citrates)
  • Scaffolds
  • Surface-mediated transfection

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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