Growth factors - Pharmaceutical Biotechnology: Concepts and Aapplications - page 282

Table 10.9 Various types of ulcers along with their underlying cause. An ulcer may simply be described as
a break or cut in the skin or membrane lining the digestive tract which fails to heal. The damaged area may
then become infl ammed

Ulcer category Description

Decubitus ulcer (e.g. bed sores, pressure sores) Ulcer due to continuous pressure exerted on a particular area

of skin. Often associated with bed-ridden patients

Diabetic ulcers Ulcers (e.g. 'diabetic leg') caused by complications of diabetes

Varicose ulcers Due to defective circulation, sometimes associated with

varicose veins

Rodent ulcers An ulcerous cancer (basal cell carcinoma), usually affecting

the face

Peptic ulcers Ulcer of the digestive tract, caused by digestion of the

mucosa by acid and pepsin. May occur in, for example, the
duodenum (duodenal ulcer) or the stomach (gastric ulcer)

diabetes, etc., remains the underlining cause of up to 50 per cent of all amputations carried out in
the USA.
The fl uid exuded from a fresh or acute wound generally exhibits high levels of various growth
factors (as determined by bioassay or immunoassay analysis). In contrast, the concentration of
such mitogens present in chronic wounds is usually several-fold lower. Direct (topical) applica-
tion of exogenous growth factors results in accelerated wound healing in animals. Although some
encouraging results have been observed in human trials, the overall results obtained thus far have
been disappointing. Having said this, one such factor (rPDGF, tradename Regranex; Table 10.2)
has been approved for topical administration on diabetic ulcers. Future studies may well also
focus on application of a cocktail of growth factors instead of a single such factor to a wound
surface.
A greater understanding of wound physiology/biochemistry may also facilitate greater suc-
cess in future trials. It has been established, for example, that the fl uid exuded from chronic
wounds harbours high levels of proteolytic activity (almost 200-fold higher than associated with
acute wounds). Failure of mitogens to stimulate wound healing may thus be due, in part, to their
rapid proteolytic degradation (and/or the degradation of growth factor receptors present on the
surface of susceptible cells). Identifi cation of suitable protease inhibitors, and their application
in conjunction with exogenous growth factor therapy, may improve clinical results recorded in
the future.
Overall, therefore, a range of growth factors may demonstrate potential in wound manage-
ment/healing, or for other therapeutic indications. A summary of these factors and their biological
activities/potential, therefore, constitutes the remainder of this chapter.

10.3.1 Insulin-like growth factors

The IGFs (also termed 'somatomedins'), constitute a family of two closely related (small) polypep-
tides: IGF-I and IGF-II. As the names suggest, these growth factors bear a strong structural
resemblance to insulin (or, more accurately, proinsulin). Infusion of IGF-I decreases circulating