Many different types of trauma result in skin injury. The body is usually capable of closing these wounds spontaneously to restore its protective function as a barrier and maintain homeostasis. In lower vertebrates, complete tissue regeneration can occur, whereas in higher vertebrates the loss of normal architecture results in a fibro-proliferative response, producing a scar.

Delay in healing may occur with large wounds or impaired tissue viability and results in enhanced scarring. “Healing” is often considered as complete when a wound is epithelialized, although cellular  events continue   for months or years.Non-healing or chronic wounds take a  great toll on diabetic and venous insufficiency patients in terms of morbidity and mortality, while incurring great health-care expenditure. The quest for wound healing agents is perhaps one of the oldest challenges for medical practice, and various treatments have long been recorded in ancient writings.

In the late 20th century, we have moved from an era of solely removing noxious influences (e.g. infection, inflammation, necrotic tissue) and pain control, to one in which we visualize the healing process being positively fostered. Recently, much attention has been focused on early foetal wound healing, which is so nearly perfect as to be considered scarless. Manipulation of adult wounds with the aim of producing “scarless” healing and full regeneration is currently a Utopia, which may never be reached. We still need a deeper understanding of tissue repair mechanisms in order to intervene at cellular or molecular levels. The best we can hope for is to pharmacologically reduce the time to heal, the cost of care in certain cases, and to modify to some extent the end result of function and cosmesis. Since the discovery of the first growth factor, it has been shown that cellular events in wounds could be potentially accelerated.

Such agents in experimental trials are usually delivered topically and, therefore, have different pharmacodynamics and kinetics from conventional, orally administered drugs. Unlike topical agents administered through transdermal devices, vulnerary agents are intended to localize and exert their effect in the wound only. Therefore, serum concentrations will not reflect their efficacy, but only indicate possible toxicity if systemic absorption were to take place. The need to establish this new discipline of wound pharmacology was recognized by the European Tissue Repair Society in 1995, which encouraged new criteria for the evaluation of the safety and efficacy of topically applied wound healing agent.

One such agent, phenytoin, has a common side-effect with treatment. It is the development of fibrous overgrowth of the gingivae, although mild skin and skull thickening may also occur. This apparent stimulatory effect on connective tissue suggests an exciting possibility for use in wound healing. Despite numerous clinical trials and case studies carried out world-wide, the mechanism of action of PHT in promoting wound healing is still unknown.