Adenoviral-mediated overexpression growth factor-B corrects ischemic of platelet-derived impaired wound healing

Chronic wounds represent a major clinical problem with significant morbidit y and healthcare expenditures, but no effective therapies. Topical platelet -derived growth factor-BB trials have required large and repeated doses to achieve only a modest effect, We examined the ability of an adenovirus cont aining the platelet-derived growth factor-B transgene to improve the rate o f wound healing through induction of platelet-derived growth factor-B overe xpression in cells participating in the wound healing response, We treated excisional wounds in the ischemic rabbit ear, which have a 60% delay in hea ling, with vehicle, 10(6), or 10(8) plaque-forming units of an adenovirus c ontaining the platelet-derived growth factor-B per wound (n = 19). At 7 d t his resulted in a decrease in the epithelial gag from 3.4 +/- 1 nlm (mean /- SD) in vehicle-treated wounds to 1.9 +/- 1.8 mm (mean +/- SD, p < 0.05) when treated with 106 plaque-forHling units of an adenovirus containing the platelet-derived growth factor-B, and 0.7 +/- 1.1 mm (mean +/- SD, p < 0.0 01) when treated with 10(8) plaque-forming units of an adenovirus containin g the platelet-derived growth factor-B, Ischemic excisional wounds treated with 108 plaque-forming units of an adenovirus containing the platelet-deri ved growth factor-B even healed more rapidly than non-ischemic excisional w ounds treated with vehicle (p < 0.05), In contrast, 5 mu g of platelet-deri ved growth factor-BB protein (n = 2) resulted in only modest granulation ti ssue at the margin, but no significant differences in epithelial gap (3 +/- 0.6 mm, mean +/- SD), Plaque-forming units (10(6) or 10(8)) of an adenovir us containing the beta-galactosidase transgene (n = 4) impaired wound re-ep ithelialization with an epithelial gap of 5.11 +/- 0.69 mm, mean +/- SD, p < 0.004, and 3.8 +/- 0.57 mm, mean +/- SD, p < 0.07, respectively, Adenovir al-mediated gene transfer of platelet-derived growth factor-B overcame the ischemic defect in wound healing and offers promise in the treatment of chr onic nonhealing wounds, The vulnerary effects of platelet-derived growth fa ctor-B overexpression were sufficient to overcome the adverse effects of th e adenovirus or transgene on wound healing.