The contribution of plasmid design and release to in vivo gene expression following delivery from cationic polymer modified scaffolds

Misael O. Avilés, Chia Hsuan Lin, Marina Zelivyanskaya, John G. Graham, Ryan M. Boehler, Phillip B. Messersmith, Lonnie D. Shea*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Tissue engineering scaffolds capable of gene delivery can provide a structure that supports tissue formation while also inducing the expression of inductive factors. Sustained release strategies are hypothesized to maintain elevated plasmid concentrations locally that can enhance gene transfer. In this report, we investigate the relationship between plasmid release kinetics and the extent and duration of transgene expression. Scaffolds were fabricated from polymer microspheres modified with cationic polymers (polyethylenimine, poly(l-lysine), poly(allylamine hydrochloride), polydiallyldimethylammonium) or polydopamine (PD), with PD enhancing incorporation and slowing release. In vivo implantation of scaffolds into the peritoneal fat pad had no significant changes in the level and duration of transgene expression between PD and unmodified scaffolds. Control studies with plasmid dried onto scaffolds, which exhibited a rapid release, and scaffolds with extended leaching to reduce initial quantities released had similar levels and duration of expression. Changing the plasmid design, from a cytomegalovirus (CMV) to an ubiquitin C (UbC) promoter substantially altered the duration of expression. These studies suggest that the initial dose released and vector design affect the extent and duration of transgene expression, which may be sustained over several weeks, potentially leading to numerous applications in cell transplantation and regenerative medicine.

Original languageEnglish (US)
Pages (from-to)1140-1147
Number of pages8
JournalBiomaterials
Volume31
Issue number6
DOIs
StatePublished - Feb 2010

Keywords

  • Cationic polymers
  • Layered scaffolds
  • Polydopamine
  • Sustained gene delivery
  • Tissue engineering
  • Ubiquitin

ASJC Scopus subject areas

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

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