EFFECTS OF HETERODIMERIC ISOFORM OF PLATELET-DERIVED GROWTH-FACTOR PDGF-AB ON WOUND-HEALING IN THE RAT

Earlier wer reported a positive effect of platelet-derived growth factor (PDGF-BB) on rat wound healing while corresponding doses of PDGF-AA were not as effective. The present work was undertaken to study the effects of the heterodimeric form of PDGF (PDGF-AB) on wound healing in rats. Subcutaneously implanted hollow cylindrical cellulose sponges served as an inductive matrix for the granulation tissue. Fifty microliters of solutions containing 0, 5, 50 or 500 ng of PDGF-AB heterodimer were injected daily into the sponges. The analyses of the granulation tissue in the sponge cylinders were carried out 7 days after implantation. Injections of 500 ng of PDGF-AB stimulated significantly the accumulation of collagen and proteins, indicated by the elevated hydroxyproline and nitrogen content of the sponge (+ 51%, p < 0.01 and + 48%, p < 0.001, respectively). Similarly, the amounts of DNA, RNA, hexosamines and uronic acids were significantly higher, reflecting a PDGF-AB-induced increase in the cellularity and glycosaminoglycans. Analyses of wound fluid showed a marked decrease in the number of polymorphonuclear leukocytes in response to PDGF-AB treatment. Injections of a lower dose, 50 ng, of PDGF-AB increased significantly the mean amounts of nitrogen, RNA and uronic acids but no significant changes were observed in other parameters. The lowest dose of PDGF-AB, 5 ng daily, induced no essential effect. In vitro PDGF-AB increased the number of rat granulation tissue-derived fibroblasts and collagen accumulation per culture dish at concentrations of 10 and 30 ng/ml. To conclude, PDGF-AB accelerates dose-dependently granulation tissue formation in experimental wounds. Correspondingly, PDGF-AB stimulates the proliferation of granulation tissue-derived fibroblasts in culture.