Research Angiogenesis and Wound Healing

Angiogenesis is the generation of new blood vessels and a critical component of wound healing.⁹⁶ This is true because new blood vessels are necessary in the area of the wound for the dissemination of growth factors, as well as additional chemical regulators such as MMPs (matrix metalloproteinases) which stimulate angiogenesis. Thus, the initiation of angiogenesis in a wound in turn results in increased angiogenesis based on the enhanced presence of the various chemical factors necessary for wound healing.

Angiogenesis is a complex process in which different types of cells interact to ultimately generate new blood vessels. Key among these are macrophages which secrete various growth factors (principally vascular endothelial growth factor—VEGF and basic fibroblast growth factor—bFGF), and which "work with" platelets, which secrete platelet derived growth factor—PDGF—to form new tissue. Growth factors are key building blocks of new tissue including blood vessels. Because more than 30 different chemical agents have been identified in the wound healing process, all of which are either initiated or enhanced by angiogenesis, the angiogenic process is one that merits continued intensive investigation.

In the context of wound healing, it has yet to be determined exactly which growth factors are the most efficacious in the repair and healing of a wound. Numerous studies have been conducted on the various growth factors and their efficacy with the healing of chronic wounds. Although evidence suggests that certain growth factors may be more effective than others, much work is still required to pinpoint the exact mechanisms of healing in re angiogenesis, growth factors and chronic wounds. One of the key areas of investigation in this context utilizes gene array technology to attempt to isolate the molecular mechanisms underlying cellular processes. The understanding of genetic activity will do much to clarify the specific activity that comprises angiogenesis.

Current research, supported by an NIH National Institute of Diabetes and Digestive and Kidney Diseases Mentored Clinical Scientist Development Award, is investigating local angiogenic therapy for diabetic foot ulcers via polymer-based delivery of growth factors, specifically VEGF. One of the critical factors in assessing response in underlying tissue is toxicity, based on both the dosage of growth factor delivered as well as the delivery method itself. Angiogenesis will be impaired if either the growth factor dosage or the delivery mechanism (or both) causes some degree of toxicity.