Acceleration of skin graft healing by growth factors

Abstract

A special local burn wound treatment, using a healing promotion factor, attempted to achieve earlier wound closure. Clinically it is not difficult to harvest autologous human platelet-derived wound healing factor (HPDWHF) from burn patients. Another study has proved that porcine pituitary extract (PPE) could be one of the supplements for growing human keratinocytes in vitro (Wang HJ, Chen TM, Tung YM et al. Burns 1995 3). Initially, using the ELISA immunoassay, we detected titres of platelet-derived growth factor heterodimer AB (PDGF-AB) and epidermal growth factor (EGF) in HPDWHF and PPE. After elevating a 6 × 9 cm 2 flap on the backs of Sprague-Dawley (SD) rats 1 ml of heterologous HPDWHF and PPE were sprayed topically on the wound and followed by grafting six pieces of 1 cm 2 autologous full-thickness skin. The flap wound was then closed with a piece of large-pore Biobrane interposed between the skin graft wound and the flap. On postgraft day 7, the wound was reopened to measure the area of the full-thickness skin graft (FTSG) using micrographic paper; the results are reported as the percentage of graft expansion beyond the original size. In the cytokine study, we found that the concentrations of PDGF-AB dimer in HPDWHF and PPE were 5222 ± 102 and 375 ± 12 pg/ml (both values are reported after a 1:10 dilution) ( n = 3), whereas the EGF concentration was 245 ± 9 pg/ml, and undetectable in undiluted PPE ( n = 3), thereby proving that the PDGF-AB and EGF titres in the HPDWHF were significantly higher than in the PPE. Both the HPDWHF ( n = 6, with each animal grafted with six skin graft samples) and PPE ( n = 7) demonstrated significant accelerations of FTSG growth, with 14.41 ± 1.08 per cent and 13.16 ± 3.25 per cent increases in the FTSG size when compared to the sham control group 1.39 ± 3.26 per cent ( n = 5) ( P < 0.05). Comparisons between the treatment groups showed no evidence to indicate that the HPDWHF is superior to the PPE in accelerating FTSG growth ( P > 0.05). This supports the hypothesis that PDGF appears to transduce its signal through wound macrophages and may trigger the induction of positive autocrine feedback loops and synthesis of endogenous wound PDGF and other growth factors, thereby enhancing the cascade of tissue repair (Pierce GF, Mustoe TA, Altrock B et al. 1991; J Cell Biochem 1991; 45: 319–326), and the effect that PDGF-AB on wound healing is not dose dependent (Mustoe TA, Cutler NR, Allman RM et al. Arch Surg 1994; 129: 213–219). In future studies we expect to show that autologous HPDWHF and heterologous PPE will promote skin graft wound healing in burn patients since they contain a high concentration of PDGF-AB.