A clinical model of dermal wound angiogenesis

Full-thickness dermal biopsies were performed in healthy volunteers to establish the range of angiogenic responses in wound healing in a normal population. Four-millimeter punch biopsies were made in the forearms of 15 healthy volunteers. Each wound was evaluated microscopically 4–5 times per week for 2 weeks. A semiquantitative wound scoring system to evaluate the neovasculature at the wound periphery was investigated. A vascular score was calculated for each wound at each observation. Two independent observers analyzed the microscopic wound images using the scoring system. At the end of the 14-day period, repeat biopsies were performed on some of the volunteers, and the granulation tissue was stained with anti-CD31. The Kaplan-Meier method was used to estimate the distribution of the time to reach predetermined target average vascular scores. A mixed-effects regression model indicated that time, age, and observer were predictors for the average vascular score outcome. The pattern and time course for wound neovascularization was highly reproducible in this group of healthy volunteers, and the assay was feasible and well tolerated. This wound angiogenesis model may be useful for monitoring the effects of antiangiogenic agents on normal wound neovascularization. (WOUND REP REG 2003;11:306–313) Agents targeting angiogenesis have shown promise preclinically for the treatment of cancer and other diseases, and dozens of antiangiogenic agents are now in clinical trials. One of the challenges of studying this new class of compounds is defining relevant end points of drug efficacy. Dosing cannot be based upon dose limiting toxicities or a maximal tolerated dose because these agents are expected to have only modest toxicity. Based upon preclinical models, these agents may lead to tumor dormancy or inhibit tumor growth rather than cause tumor shrinkage or radiographic tumor regression, which are the traditional