Topical treatment with growth factors for tympanic membrane perforations: progress towards clinical application.

Basic scientific research has demonstrated that epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-AA (PDGF-AA) and transforming growth factor-alpha (TGF-alpha) are induced by acute tympanic membrane (TM) perforation. The expression of these growth factors peaks during the inflammatory phase and then declines, suggesting their involvement in the healing process of the TM. Expression of EGF receptor, bFGF receptor, PDGF receptor and keratinocyte growth factor (KGF) receptor in the TM has also been reported. Identification of these receptors indicates that the target cells in the TM may be stimulated during the process of healing by the corresponding exogenous growth factor in vivo. Some reports from animal studies showed encouraging effects of EGF, bFGF and PDGF-AA in terms of accelerated or enhanced healing of acute and chronic TM perforations without significant adverse effects. Two reports of clinical trials of topical application of EGF or bFGF for TM perforations revealed mixed results. In this article special considerations for future directions of research into growth factors are discussed and related articles on healing of skin wounds and other lesions are reviewed. Further experimental and clinical studies on the mechanism of action of growth factors, timing of application, selection (either singly or in combination), delivery mode, dose and safety aspects, as well as more clinical trials, are warranted, and will pave the way for clinical application.