Delivery of PEI-condensed DNA via a porous polymer scaffold for tissue engineering applications

An attractive approach to tissue engineering is the delivery of therapeutic plasmid DNA through biodegradable polymers. However, the low transfection efficiency of naked DNA might be a limitation. Poly(ethylenimine) (PEI) has been shown to be highly effective as a non-viral gene delivery vehicle and we hypothesized that local delivery of condensed DNA in a three dimensional biodegradable scaffold will enhance transfection efficiency compared to that of uncondensed DNA. To address this, we optimized the characteristics of PEI-DNA condensates encapsulated within PGLA sponge formed by a gas foaming process and performed in vitro transfection studies. Release of uncondensed DNA from sponges was rapid, while release was significantly slower when condensed DNA was incorporated. In vitro transfection was observed only in sponges incorporating condensed DNA, while no transfection was observed for sponges incorporating uncondensed DNA. This study demonstrates the feasibility of incorporating freeze-dried PEI-DNA condensates within PLGA sponges using sucrose as the pore forming agent to efficiently transfect cells, and may find application in areas such as bone tissue engineering.