Collagen-embedded platelet-derived growth factor DNA plasmid promotes wound healing in a dermal ulcer model

Background. Gene therapy has shown limited efficacy for treating congenital diseases, partly due to temporary gene expression and host immune response s. Such results suggest that gene therapy is ideal for chronic wound treatm ent where limited duration of target gene expression is required. This stud y tested the wound healing effects of topically applied platelet-derived gr owth factor (PDGF)-A or -B chain DNA plasmids embedded within a collagen la ttice, Materials and Methods. Four 6-mm dermal ulcer wounds were created in the ea rs of young adult New Zealand White rabbits made ischemic by division of th e central and rostral arteries, Wounds were treated with lyophilized collag en containing PDGF-B DNA (1.0-3.0 mg), PDGF-A DNA (1.0 mg), irrelevant DNA (1.0 mg), or collagen alone. Wounds were dressed and harvested after 10 day s for measurement of granulation tissue formation, epithelialization, and w ound closure, Results were evaluated with a paired two-tailed Student t tes t, with P values < 0.05 considered significant. Results. PDGF-B DNA increased new granulation tissue (NGT) formation up to 52% and epithelialization 34% compared with controls. Wound closure was inc reased up to threefold, At 1.0 mg DNA, PDGF-A and PDGF-B stimulated similar responses. No difference in NGT or epithelialization was seen between cont rol groups. Conclusions. PDGF DNA gene therapy is effective at accelerating wound heali ng in ischemic dermal ulcers and provides a viable alternative to peptide g rowth factor therapy. (C) 2000 Academic Press.