Skin regeneration through growth hormone factors

May 1, 2005

Tokyo — Growth factors offer seemingly endless potential to skin wound repair and regeneration, yet there are several questions surrounding those that are exogenously applied to acute or chronic skin wounds, according to Xiaobing Fu, M.D., professor, Wound Healing and Cell Biology Laboratory, Burns Institute, The General Hospital of PLA, Beijing, China.

Speaking here at the LVMH Japanese and Asian Skin Research Symposium, Dr. Fu brought forward previous data supporting the use of growth factors for wound healing and his current results, further building the case for the biologically engineered applications.

With clinical findings again proving that wound healing velocity can be accelerated and its quality improved with the use of growth factors, the outcome only leads to more speculation regarding the safety, delivery method and further development of the treatments.

New data In a clinical trial with 1,530 cases from multiple centers, superficial second-degree burns, deep second-degree burns, granulation tissue wounds, donor sites and chronic wounds received treatment with recombinant bovine basic fibroblast growth factor (rbFGF) at a dose of 150 AU/cm2 per day, or normal saline with 0.1 percent heparin.

The treatment times range from 10 days (superficial second-degree burn) to 22 days (granulation tissue wounds). Notably, prior to treatment with rbFGF or placebo, all wounds were debrided and cleaned. The growth factor was dissolved in normal saline solution containing 0.1 percent heparin, and all wounds were covered with sterile cotton dressings, removing these each day for saline irrigation and reapplication of rbFGF.

"The clinical trial indicates that all of the superficial second-degree burns, deep second-degree burns, donor sites and chronic skin ulcers treated with rbFGF or epidermal growth factor (EGF) (see figure) had an accelerated rate of granulation tissue formation and epidermal regeneration as compared with that in the controls," Dr. Fu says. "While treatment with growth factors in skin wounds accelerates the wound healing velocity, the functional repair, such as regeneration of hair follicles, sebaceous and sweat glands cannot be achieved for the moment."

EGFs, FGFs, TGFs Recent new findings are responsible for engineered drugs that are now being readily used in the clinical setting, such as the epidermal growth factors (EGF), fibroblast growth factors (FGF) and transforming growth factors (TGF).

Tissue engineered skin including Integra (Ethicon), Apligraf (Organogenesis), Dermagraft (Smith and Nephew), and AlloDerm (LifeCell Corp.) also add to the arsenal of skin repair treatments, but dermatologists need to have a full understanding of these new therapeutic drugs or products - including their action mechanisms, suitable indications and possible side effects - which will make them much easier to choose the correct treatment for different wounds, according to Dr. Fu.

Future application "A mounting body of evidence suggests that exogenous growth factors are necessary for tissue repair. They may act as an inducer for endogenous growth factors and their gene expression, or as a stimulator for tissue repair cells in accelerating acute and chronic ulcer healing," Dr. Fu says. "Although their use is ongoing in clinic and their effects confirmed, further research about growth factors should be done in the future, including the study of their mechanisms and the co-effect or anti-effects."

A predominant question is what possible side effects or toxicity may be presented by growth factors used for wound healing. While some preliminary data currently supports the safe use of engineered applications without the risk of side effects, it is necessary to understand that the biological effects remain unstudied.