Gene Expression and Release of Growth Factors During Delayed Wound Healing: A Review of Studies in Diabetic Animals and Possible Combined Laser Phototherapy and Growth Factor Treatment to Enhance Healing

Objective: The purposes of this study were: to review studies of growth factors in cutaneous wounds of animals with diabetes to identify those factors with altered gene expression and content compared with nondiabetic animals; and to explore which deficiencies of growth factors in diabetic wounds may or may not be improved by laser irradiation. Background data: Wound healing is compromised in diabetes. Decreased production and/or increased destruction of growth factors may be responsible. Laser irradiation can increase the gene expression and release of certain growth factors by cells. Methods: Research articles investigating growth factor expression in wounds of nondiabetic and diabetic mice and rats published through September 2011 were retrieved from library sources, PubMed databases, reference lists of articles, and searches of relevant journals. Results: Vascular endothelial growth factor (VEGF), placental growth factor (PlGF), keratinocyte growth factor (KGF), fibroblast growth factor 1 (FGF-1), FGF-2, insulin-like growth factor 1 (IGF-1), IGF-2, transforming growth factor beta (TGF-beta), and nerve growth factor (NGF) had decreased gene expression and content in early phases of healing for diabetic wounds. Gene expression of KGF, IGF-1, and IGF-2 was delayed, whereas that of FGF-1 and FGF-2 occurred earlier, in diabetic compared with nondiabetic wounds. Conclusions: Growth factor administration combined with laser irradiation may provide an effective therapy to maximize healing of diabetic wounds.