We have proposed engineering tissues by the incorporation and sustained release of plasmids encoding tissue-inductive proteins from polymer matrices. Matrices of poly(lactide-co-glycolide) (PLG) were loaded with plasmid, which was subsequently released over a period ranging from days to a month in vitro. Sustained delivery of plasmid DNA from matrices led to the transfection of large numbers of cells. Furthermore, in vivo delivery of a plasmid encoding platelet-derived growth factor enhanced matrix deposition and blood vessel formation in the developing tissue. This contrasts with direct injection of the plasmid, which did not significantly affect tissue formation. This method of DNA delivery may find utility in tissue engineering and gene therapy applications.
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The authors gratefully acknowledge technical assistance from Jeremy Blum and Elly Liao. Financial support for this work was provided by National Institutes of Health grant 1RO1DE13004, Reprogenesis, and Selective Genetics. L.D.S. was supported by National Institute of Dental Researchtraining grant DE07057.
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