Fibrin seal in wound healing: effect of thrombin and [Ca2+] on human skin fibroblast growth and collagen production.

To assess the interaction of a fibrin sealant with wound healing, an in vitro study using human skin fibroblasts was carried out. The effect of thrombin and calcium concentrations in the sealant on the growth parameters and collagen synthesis by normal human skin fibroblasts was examined. The fibroblast proliferation was increased 3 times for 50 and 25 IU of thrombin/ml. However for 20 mM [Ca2+], this stimulating effect of thrombin was observed after an 8 day incubation period, whereas it was observed as soon as the 2nd day in the presence of 2 mM [Ca2+]. The high rate of [Ca2+] (20 mM) partly inhibited DNA synthesis: for 2 mM [Ca2+], the incorporation of [3H]-Thymidine was 4 times greater than for 20 mM [Ca2+]. Further experiments demonstrated that human skin fibroblasts in the presence of 50 IU of thrombin/ml and 2 mM [Ca2+] in fibrin seal could increase the type I and III collagen synthesis while increasing the ratio of type III to type I. Thus, our results suggest that in vivo wound healing which required fibroblast growth and collagen synthesis can be stimulated in the presence of fibrin glue which is in good accordance with previous clinical observations.