Current therapies for wound healing: electrical stimulation, biological therapeutics, and the potential for gene therapy

It has long been known that dermal wounds may show The healing of wounds results from a number of temporally impaired healing in patients with peripheral arterial occlusco-ordinated processes that involve several events driven ive disease (PAOD), deep vein thrombosis (DVT), and by locally released mediators.1–11 The first event is immedidiabetes. For example, wounds in diabetic patients heal ate and consists of the activation of the coagulation cascade very slowly or not at all when compared with wounds and the production of a blood clot. After several minutes, in nondiabetics. Despite intense investigation, the precise an acute inflammatory response ensues. Subsequently, molecular mechanisms associated with impaired healing in leukocytes clear the wound of debris and release growth this patient group are poorly understood. A number of factors to initiate the healing process. Then follows the laboratories have shown reductions in the levels of growth first stage of collagen repair involving deposition and the factors and their receptors. These include PDGF recepformation of granulation tissue which becomes a new and tors,20 IGF-I and IGF-II,21 keratinocyte growth factor temporary weak tissue. The third and final process is the (KGF),22 TGFβ and IGF-I,23 TGFβ1,2,3 and receptors.24 second phase of collagen repair resulting in extracellular Consistent with these findings, several groups have shown matrix remodeling, angiogenesis, and the reproduction of that the application of growth factors may induce the full strength tissue comparable to the original skin. Much acceleration of cutaneous wound healing in murine models of the normal healing process is driven by growth factors. of diabetes. These studies are described later. In addition to their role in blood clot formation, platelets generate a number of growth factors that are found in wound fluid, including transforming growth factor α Healthcare burden for the treatment of (TGFα), platelet-derived growth factor (PDGF), epidermal chronic wounds growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor β (TGFβ), and insulinUlcers associated with pressure and arterial and venous like growth factor I (IGF-I).12–15 In the inflammatory diseases response, neutrophil migration is induced by PDGF, Dermal ulcers are a common complication and frequent interleukin 1α (IL1α), IL8, tumor necrosis factor α (TNFα), cause of hospital admission for many patients suffering granulocyte macrophage colony-stimulating factor with diabetes. In 1992, in the UK, 2% of the diabetic (GM-CSF), and granulocyte colony-stimulating factor population were documented as having ulcer history with (G-CSF).16–19 Thus, multiple growth factors and cytokines approximately 0.5% having active ulcers at any one time.25 There is a marked increase in dermal ulcer prevalence play a major role in wound healing. 808