1. Biomaterials. 2009 Jan;30(3):394-401. Epub 2008 Oct 17.

Layered PLG scaffolds for in vivo plasmid delivery.

Rives CB, des Rieux A, Zelivyanskaya M, Stock SR, Lowe WL Jr, Shea LD.

Department of Chemical and Biological Engineering, Northwestern University, 2145 
Sheridan Road, Tech E136, Evanston, IL 60208, USA.

Gene delivery from tissue engineering scaffolds can induce localized expression
of tissue inductive factors to direct the function of progenitor cells, either
endogenous or transplanted. In this report, we developed a layering approach for 
fabricating scaffolds with encapsulated plasmid, and investigated in vivo gene
transfer following implantation into intraperitoneal fat, a widely used site for 
cell transplantation. Porous poly(lactide-co-glycolide) (PLG) scaffolds were
fabricated using a gas foaming method, in which a non-porous layer containing
plasmid was inserted between two porous polymer layers. The layered scaffold
design decouples the scaffold structural requirements from its function as a drug
delivery vehicle, and significantly increased the plasmid incorporation
efficiency relative to scaffolds formed without layers. For multiple plasmid
doses (200, 400, and 800mug), transgene expression levels peaked during the first
few days and then declined over a period of 1-2 weeks. Transfected cells were
observed both in the surrounding adipose tissue and within the scaffold interior.
Macrophages were identified as an abundantly transfected cell type. Scaffolds
delivering plasmid encoding fibroblast growth factor-2 (FGF-2) stimulated a 40%
increase in the total vascular volume fraction relative to controls at 2 weeks.
Scaffold-based gene delivery systems capable of localized transgene expression
provide a platform for inductive and cell transplantation approaches in
regenerative medicine.

PMCID: 2642007
PMID: 18929408 [PubMed - indexed for MEDLINE]