Growth factors and hormones regulate the balance between proliferation and differentiation in not only the healing wound, but also numerous other biological processes including the deregulated proliferation observed in cancer cells, n.22 The main candidates for acceleratory wound-healing treatments, such as EGF, FGFs and PDGF, either are directly involved in the signalling events that lead to malignant transformation or are upregulated in neoplastic cells.23 Moreover, concern has been expressed over the use of supraphysiological doses. Reassuringly, there has been absolutely no evidence from any clinical trials of an increased incidence of malignant cutaneous changes even after substantial follow-up periods. In addition, no trial to date has reported increased incidence of hypertrophic scar formation.
CONCLUSIONS Early experiments using PDWHF highlighted the potential benefits of exogenous growth fac- tors and hormones in the treatment of non-healing wounds.13−14 The past decade has seen the production, clinical testing and approval of several recombinant growth factors for the treatment of non-healing wounds.
In both the United Kingdom and the United States, PDGF has been specifically approved for the treatment of diabetic foot ulcers, and in China, EGF and FGF-2 have been approved for the treatment of both acute and chronic wounds.
However, specific dosing and treatment regimens have yet to be standardised for many types of non- healing wounds.
The use of growth factors as adjunct therapy to skin grafts or by incorporation into a range of artificial skin substitutes is yielding promising results for treating wounds that are very large (i.e. burns) or persistently non-healing (i.e. diabetic ulcers).
Whilst no single exogenously applied growth factor is currently able to eliminate scarring or regenerate the diverse array of structures present in normal integument, such as sweat gland and hair folli- cles, with recent advances in our understanding of cutaneous lineage determination,24 we are entering an era where this goal may soon be attainable.
Equally, single growth factors need not be employed in isolation; a combination of growth factors can be used to compliment both the existing treatment regimes, e.g.
SLPI plus EGF/FGF-2, etc.
In addition, a more detailed understanding of the role of hormones in age-related healing will allow us to use specific topical applications of oestrogen receptor agonists or downstream gene targets.
The scene is set for many exciting advances over the next decade, where a more detailed understanding of the molecular and cellular changes that lead to delayed healing will lead to the generation of more effective treatments.