Tissue engineering via local gene delivery.

The first goal of this review is to describe a local plasmid gene transfer technology known as the gene activated matrix (GAM). GAM was the first gene therapy designed specifically for tissue engineering applications, and the mechanism of action of plasmid gene transfer is closely tied to the normal sequence of events associated with wound healing. The normal sequence of wound healing events is stereotyped for most tissues, and one assumption has been that GAM could serve as a platform technology for local gene delivery in various tissues and organs. This hypothesis essentially has been proved: animal studies over the past 6 years have established that plasmid genes can be delivered to acutely injured tendon, ligament, bone, muscle, skin, and nerve. The second goal of the review is to describe the most likely "first use" of the technology in man, namely, treatment of osteoporotic hip fracture in the elderly. Although not universally appreciated, interest in osteoporotic fracture should grow because of epidemiological, surgical, and societal considerations. These considerations, plus the unmet clinical need associated with the current standard of fracture care, justify efforts to develop novel therapies for bone regeneration and repair in the elderly.