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Growth substances (cytokines and growth factors) are soluble signaling proteins affecting the process of normal wound healing. Cytokines govern the inflammatory phase that clears cellular and extracellular matrix debris. Wound repair is controlled by growth factors (platelet-derived growth factor [PDGF], keratinocyte growth factor, and transforming growth factor β). Endogenous growth factors communicate across the dermal-epidermal interface. PDGF is important for most phases of wound healing. Becaplermin (PDGF-BB), the only growth factor approved by the Food and Drug Administration, requires daily application for neuropathic wound healing. Gene therapy is under development for more efficient growth factor delivery; a single application will induce constitutive growth factor expression for weeks. Based on dramatic preclinical animal studies, a phase 1 clinical trial planned on a PDGF genetic construct appears promising.