title: Treatment of avascular ulcers with cytokine-induced tissue generation and skin grafting.
abstract: 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 granulated 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.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, Missouri USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Brown
authors.forename: S H
authors.initials: SH
authors.lastname: Chung
authors.forename: E N
authors.initials: EN
authors.lastname: Pasia
authors.forename: R K
authors.initials: RK
authors.lastname: Khouri
mesh_terms: D000818:Animals; D010982:Platelet-Derived Growth Factor / Q000627:therapeutic use*; D011817:Rabbits; D011994:Recombinant Proteins; D016038:Skin Transplantation; D012883:Skin Ulcer / Q000601:surgery*
chemical_list: D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins