Treatment of avascular ulcers with cytokine-induced tissue generation and skin grafting

Background Recombinant platelet-derived growth factor (rPDGF-BB) stimulates migration and proliferation of fibroblasts and smooth muscle cells and induces the rapid development of granulation tissue. This study investigated the use of rPDGF-BB and skin grafting to heal avascular ulcers using a rabbit model. We further investigated the effect of a hyaluronic acid carrier and a vascular pedicle on rPDGF-induced tissue generation in this model. Methods Large avascular ulcers were created on both ears of New Zealand white rabbits. One ulcer was treated with topical rPDGF-BB, the other with control buffer. After 5 or 7 days, the amount of granulation tissue migration from the wound margin was measured, and the wounds were skin grafted. In another group of ulcers, rPDGF-BB treatment was combined with a hyaluronic acid disk or an intact central axial ear artery and vein. Results Whereas control wounds generated 1.00 ± 0.27 mm and 1.75 ± 0.25 mm of granulation tissue migration from the wound margin by days 5 and 7, respectively, rPDGF-BB treatment increased the amount of granulation tissue migration to 1.88 ± 0.23 mm and 3.00 ± 0.86 mm by days 5 and 7 after treatment, respectively (P< 0.05 at both time points). Hyaluronic acid disks stimulated 2.50 ± 0.22 mm of granulation tissue migration by day 7 in controls; when rPDGF-BB was added to the carrier, the migration increased to 4.50 ± 0.29 mm from the wound margin (P< 0.05). Granulation tissue migration was further increased with an intact vascular pedicle: 5.75 ± 0.48 mm in controls versus 7.75 ± 0.25 mm with rPDGF-BB treatment (P< 0.01). Skin grafts applied to the treated ulcers failed to survive in all groups except those with intact vascular pedicles. Conclusions This study demonstrates that rPDGF-BB can increase the amount of granulation tissue generated over an avascular wound. This tissue generation is enhanced by both a hyaluronic acid carrier and a vascular pedicle. A vascular pedicle was required for skin graft survival. This study supports the role of hyaluronic acid in rPDGF-BB-induced tissue generation and the requirement of a direct blood supply for functional cytokine-induced tissue generation