The effect of epidermal growth factor on granulation tissue formation in the rat.

Subcutaneously implanted cylindrical hollow viscose cellulose sponges were used to investigate the effects of locally applied EGF on developing granulation tissue. The test implants were treated with a single or daily injections of a solution containing 0.2, 1 or 5 micrograms of EGF in 0.1-0.5% albumin while the control implants were treated correspondingly with the carrier solution only. Analyses of wound fluid and granulation tissue in the sponge cylinders were carried out 7 or 10 days after implantation. After daily application of EGF a stimulatory effect on granulation tissue formation was observed: cellularity increased as demonstrated by the elevated amounts of nucleic acids, and the accumulation of collagen and glycosaminoglycans was enhanced. The effect was dose-dependent. After a single application of EGF no essential differences were detected in wound fluid prostaglandin E2 levels or measured components of granulation tissue between the groups. Thus daily application of EGF was necessary to obtain an augmenting effect on granulation tissue formation. EGF seemed to be a potent mitogen for fibroblastic cells released from experimental granulation tissue in a dose-dependent manner. EGF treatment inhibited the production of radioactive hydroxyproline. The decreased rate of collagen synthesis was also indicated by decreased amounts of procollagen mRNAs. In the EGF-treated rats granulation tissue blood flow was significantly higher than that in the control rats 7 days after implantation. In both groups blood flow values of the incision scar region were significantly higher than those of the lumbar skin, but no intergroup differences were detected. In implants injected with EGF the albumin extravasation clearly exceeded that of the control implants. Albumin extravasation in the incision scar region was higher than that in the lumbar skin in both groups. EGF treatment increased procollagen mRNA, particularly at day 4. To study the influence of EGF on methylprednisolone-induced inhibition of granulation tissue formation, the sponge cylinder was injected immediately after implantation with a single dose of 2 mg (approximately equal to 1.7 x 10(-3) M) of depot methylprednisolone. This methylprednisolone injection resulted in a significant fall in the accumulation of nucleic acids, collagen and glycosaminoglycans. After daily injections of EGF these parameters returned to levels close to the control values. In the presence of methylprednisolone EGF could not increase collagen synthesis of fibroblastic cells.(ABSTRACT TRUNCATED AT 400 WORDS)