EFFECT OF TOPICAL RECOMBINANT TGF-BETA ON HEALING OF PARTIAL THICKNESS INJURIES

Peptide growth factors produced by platelets, macrophages, epidermal, and dermal cells may play key roles in regulating healing of partial-thickness skin wounds. We examined the effects of recombinant transforming growth factor β (TGF-β) on cultures of epidermal and dermal cells in vitro and on healing of partial-thickness injuries in vivo. Increasing concentrations of TGF-β (0.1, 1, and 10 ng/ml) progressively inhibited serum-stimulated DNA synthesis by up to 95% in cultures of adult human keratinocytes during 48 hr of exposure to TGF-β. In contrast, TGF-β (10 and 100 ng/ml) in serum-free media stimulated DNA synthesis by up to 80% compared to serum-free control cultures of adult human dermal fibroblasts. To evaluate the effects of TGF-β on healing of partial-thickness injuries in vivo, wounds (20 × 20 × 0.6 mm) were created on the dorsal thoracolumbar region of adult pigs by an electrokeratome and were treated daily for 5 days after injury with vehicle or vehicle containing 0.1 or 1 μg/ml TGF-β and covered with occlusive dressing. Computerized planimetry of wound photographs demonstrated that TGF-β treatment stimulated statistically significantly increases in the area of regenerated epidermis compared to wounds treated with saline vehicle on Days 3, 4, 5, and 7 after injury probably due to TGF-β increasing the rate of epidermal cell migration. In addition, morphometry of biopsy specimens showed that TGF-β treatment stimulated statistically significant increases in the cross-sectional depths of regenerated dermis compared to wounds treated with saline or Silvadene vehicles on Days 5, 6, and 8 after injury. On Day 10 after injury, when epidermal regeneration was complete, cross-sectional depths of all wounds were similar. These results demonstrate that TGF-β is a bifunctional regulator of cell mitosis in vitro and that repeated topical treatment with TGF-β promotes healing of epidermal and dermal components of partial-thickness wounds. Additional experiments are needed to determine if topical treatment of partial-thickness injuries with TGF-β will have clinically relevant effects on healing. © 1991.