Current Insights On Growth Factor Therapy

By Patris A. Toney, DPM, MPH, and Vickie R. Driver, DPM, MS

The future of growth factor therapy in wound care is advancing rapidly. There is also increasing evidence in the literature to support the efficacy of growth factors in wounds, particularly chronic wounds, and how they can help facilitate desired healing outcomes. With advances in research over the past decades, physicians and researchers have teamed together to isolate and identify the disruption(s) in the sequence of wound healing that lead to chronic wounds.

Upon a closer examination of the phases of wound healing on the cellular level, it is clear that cytokines, particularly growth factors, play significant roles. The direct functions of growth factors exert an effect or effects on multiple processes during wound healing. By looking at the phases of wound healing which are catalysts for the production of growth factors and are also stimulated by the growth factors, one can gain insight into how direct or indirect application of growth factors can help heal chronic wounds.

A Guide To The Wound Healing Continuum
Wound healing proceeds through three phases: inflammation, fibroplasia and maturation.1-4 Beginning with an initial injury, the inflammatory phase ensues after a brief introductory period of immediate vasoconstriction replaced by vasodilation. This vasodilation serves as a pipeline and funnels the unfolding inflammatory cascade. During this time, platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor a and transforming growth factor ß (TGF-ß) are released from the alpha granules of platelets secondary to degranulation.2-4

As the inflammatory phase tapers around the sixth day after the injury has occurred, fibroblastic proliferation begins. During proliferation, present fibroblasts stimulate angiogenesis and other circulating, sensitive growth factors.1-4

While fibroplasia wanes around the third week after the injury, fibroblasts persist into maturation. Maturation comprises collagen production and can last up to two years or more.2-4

Aside from the context of the phases of wound healing, the process of wound healing may further be distinguished or categorized as acute or chronic. In the normal sequence of acute wound healing, the phases not only overlap but are also mutually dependent. On the contrary, chronic wounds persist primarily in the inflammatory phase. In effect, the link to fibroplasia fails.

Understanding The Roles Of Growth Factors
Proliferating capillaries bring oxygen and micronutrients to growing tissues and remove metabolic waste products. All types of chronic wounds, including diabetic foot infections (DFUs), are insufficient in their ability to generate angiogenesis (neovascularization).5 One may apply angiogenic stimulators to DFUs to speed neovascularization. Angiogenesis is essential for wound healing.

In 2002, Loots and colleagues found that fibroblasts extracted from diabetic ulcers demonstrated “retarded” healing and are often frozen in an inert state that requires debridement or the external application of (isolated) growth factors.6 Isolated growth factors include PDGF, EGF, insulin-like growth factor (IGF), transforming growth factor (TGF), keratinocyte growth factor (KGF) and fibroblast growth factor (FGF).

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