THE HISTORY OF UNDERSTANDING THE ROLE OF GROWTH-FACTORS IN WOUND-HEALING

During the first half of the twentieth century researchers focused the ir attention on the cellular events of wound healing. At that time Car rel made the observation that plasma rather than serum was required fo r successful tissue culture. He also identified tissue extracts which would stimulate wound healing. His research was cut short by the First World War, when he had to return to more fundamental areas of wound r esearch, where he also made major contributions important to this day. Carrel's search for a factor which would stimulate wound healing was continued by other physicians until in 1954 Dunphy's studies failed to find such a factor. At the same time another line of research was dev eloping. Basic scientists discovered mitogens and growth factors and g ave them names based on what now seem whimsical ideas of what they did . Epidermal growth factor, for example, was discovered as urogastrone, so named because it was found in the urine of pregnant women and it i nhibited gastric secretion. Ln the 1970's it became clear that the mit ogens sought by Carrel were growth factors found in platelets, and tha t wound healing was perpetuated by similar factors produced by macroph ages. Knighton reported a series of patients whose chronic wounds were healed by good wound care coupled with a complex mixture of these gro wth factors. Since then attempts have been made to induce healing usin g single recombinant factors. These attempts have been largely unsucce ssful. It is now clear that growth factors work like the coagulation c ascade. Individual factors work with eachother and in sequence creatin g a biochemical symphony. At present we know some of the instruments o f the orchestra but do not know when each should play or how many of e ach are required.