Exploring The Potential Of Growth Factors In Chronic Wounds

Clinical Editor: Lawrence Karlock, DPM
al., which showed that PDGF decreased the time to complete healing by 32 percent (86 days versus 127 days).    The adjunctive combination of PDGF and vacuum-assisted closure (VAC therapy, KCI) has been intriguing, according to Dr. Serena. He says they apply PDGF in a thin layer, wait five minutes for the PDGF to “saturate receptors” and then apply VAC therapy. Dr. Serena says he is frequently asked if the VAC vacuums out the PDGF. This is no longer an issue five minutes after one has applied PDGF, counters Dr. Serena. He says the biologic agent stimulates receptors and initiates a cascade of cellular events that lead to cell stimulation and proliferation.     “This mechanism of action suggests that the wound only needs to be exposed to PDGF briefly to exert PDGF’s full effect,” explains Dr. Serena. “As a result, we have broadened our use of PDGF, particularly in combination with other wound care products.”    However, Dr. Rosenblum says he cautions patients that there is no magic bullet and emphasizes the importance of patient compliance.     “Failure to comply with explicit instructions to remain completely offloaded will predictably result in failure, which, in turn, would never justify the costs associated with application of topical growth factor therapy,” maintains Dr. Rosenblum.    Q: Do the results of these growth factor products justify the costs?    A: All the panelists believe the costs are justified. Dr. Serena suggests most would say chemotherapy for colon and breast cancer patients justifies the costs. He notes the one- and five-year mortality rates of diabetic patients who undergo a below-the-knee amputation (BKA) are higher than the mortality rates of patients with breast or colon carcinoma (see chart above).     “PDGF is ‘chemotherapy’ for the diabetic foot,” says Dr. Serena. “The cost of PDGF in limb preservation in the diabetic patient is not only justified but it seems unconscionable not to use these agents when the patient’s survival is in jeopardy.”    Dr. Woods says the cost is justified with appropriate patient selection. When patients with diabetes have a debrided and uninfected foot or ankle wound, and adequate peripheral circulation, they should have a reasonable result, according to Dr. Woods. Dr. Weber points out that multiple studies have proven the efficacy of PDGF in treating diabetic foot ulcers.     “PDGF has been shown to increase the incidence of complete healing as well as the healing rate of diabetic foot ulcers,” explains Dr. Weber.    Although it may cost more in the short run to heal a chronic wound more quickly, Dr. Rosenblum believes the short-term costs may be justified by the results of growth factors and the earlier return to work and reduced risk of infection since the wound heals faster. He says the costs are also justified by the decreased requirements for surgical intervention and prolonged dressing care along with the decreased costs associated with manpower.    Dr. Karlock concurs and notes that he has had success using Dermagraft (Smith and Nephew) and Apligraf (Organogenesis) to close wounds.    Q: What new growth factors do you see on the horizon for possible use in wound care?    A: Dr. Woods believes growth factors that stimulate keratinocytes and the epithelium will also have a future in wound healing.     “Whereas PDGF stimulates fibroblasts, which lay down a collagen matrix, other growth factors such as epidermal growth factor (EGF) and GMCSF could work in conjunction to lay down the epithelium that covers the collagen,” explains Dr. Woods.    According to Dr. Rosenblum, there has been some promising work with basic fibroblast growth factor (bFGF), the aforementioned EGF and transforming growth factor beta (TGF-beta). Dr. Weber concurs. He notes that researchers have shown EGF enhances the healing of diabetic foot ulcers and TGF-beta promotes wound healing.

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