Diabetic foot ulceration stands as one of the most costly and debilitating complications of diabetes and remains the leading cause of nontraumatic lower extremity amputation in the United States. Traditionally, ischemia, neuropathy, trauma, and infection were considered the culprits of the recurring chronic wound and treatment revolved largely around wound debridement and revascularization. However, recent investigations have uncovered an impaired cutaneous wound healing process in diabetes caused by cellular and molecular alterations in the diabetic microenvironment and have subsequently identified an array of potential molecular targets for intervention. Here, we review recent patents describing upcoming molecular technologies at various stages of development for treating foot ulceration in the diabetic patient. Target classes reviewed include immunomodulators, neuropeptides, and growth factors, and targets reviewed include lactoferrin, thymosin beta 4, T cell immune response cDNA 7, substance P, neuropeptide Y, vascular endothelial growth factor, fibroblast growth factor, nerve growth factor, connective tissue growth factor, hepatocyte growth factor, homeobox genes, and treprostinil. In the course of this presentation, the biology of wound healing and the pathobiology of impaired wound healing in diabetes are emphasized to illustrate how these future molecular therapeutics are intended to counteract disease pathology and promote normal wound repair.
Wound healing, diabetic foot ulceration (DFU), talactoferrin (TLF), substance P (SP), neuropeptide Y (NPY), thymosin beta 4 (Tβ4), T cell immune response cDNA 7 (TIRC7), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), nerve growth factor (NGF)
Microcirculation Laboratory, Beth Israel Deaconess Medical Center, Palmer 317, West Campus, OneDeaconess Rd., Boston, MA 02215, USA.