The inability to deliver growth factors locally in a transient but sustained
manner is a substantial barrier to tissue regeneration. Systems capable of
localized plasmid gene delivery for prolonged times may offer lower toxicity
and should be well-suited for growth factor therapeutics. We investigated
the potency of plasmid gene delivery from genes physically entrapped in a
polymer matrix (gene activated matrix) using bone regeneration as the endpoint
in vivo. Implantation of gene activated matrices at sites of bone injury was
associated with retention and expression of plasmid DNA for at least 6 weeks, and with the induction of centimeters of normal new bone in a stable, reproducible, dose- and time-dependent manner.
