Treatment of Chronic Leg Ulcers with a Human Fibroblast-Derived Dermal Substitute: A Case Series of 114 Patients

A. Hjerppe, MD;[1] M. Hjerppe, MD;[1] V. Autio, Bsc;[2] R. Raudasoja, MD;[3] A. Vaalasti, MD, PhD[1]


Leg ulceration is a common disorder, though the incidence and prevalence have not been well established. It is estimated that 0.12 to 0.19 percent of Western populations have leg ulcers, and in people aged 65 or older the prevalence of venous leg ulcers is estimated at 1.0 to 3.3 percent. Seventy to 81 percent of leg ulcers are caused by venous disease, and arterial disease accounts for another 10 to 25 percent, which may coexist with venous disease. Coexisting rheumatoid disease occurs in nine percent of wound patients, whereas diabetes mellitus is present in 5 to 12 percent of patients. Less commonly, trauma, pressure, inflammatory disorders, and infectious agents also are causes of leg ulcers. The overlap of various causes, as well as coexisting disease, occurs because these conditions are not mutually exclusive.[1–7]

Because leg ulceration is a condition characterized by chronicity and relapse, it gives rise to massive healthcare expenditure. In the European countries, the care of patients with venous leg ulcers consumes 1 to 2 percent of the overall healthcare resources.[8] A chronic wound is predisposed to secondary infections, which can lead to amputations, which in turn are associated with increased mortality. Each person with a chronic wound suffers from pain and discomfort, and a chronic wound entails restrictions in a person’s everyday life and social activities.[9]

Since most leg ulcers are of venous origin, they can be healed with compression therapy alone or combined with local treatments. In recent years, the concept of a clean, moist environment has been widely accepted in the treatment of leg ulcers. In some cases, however, a moist environment and compression therapy are not sufficient for the ulcer to heal, and for these hard-to-heal ulcers, the development of tissue-engineered products can offer new options for treatment.[10,11]

A tissue-engineered human dermal substitute (HDS) (Dermagraft®, Smith & Nephew Inc., Largo, Florida) is designed to replace the dermis and to provide essential stimulatory growth factors for wound healing. It contains living human fibroblasts obtained from neonatal foreskins seeded onto a bioabsorbable polyglactin mesh.[12,13] The HDS pieces are stored frozen at -70°C until used. Although the precise mechanism of action of tissue-engineered dermis is not completely understood, it has been shown to provide elements to the wound bed that are believed to be important in the repair process. HDS provides live, nonsenescent fibroblasts capable of colonizing the wound bed and persisting in situ for several weeks. The fibroblasts are capable of secreting a number of cytokines and growth factors, including platelet-derived growth factor, insulin-like growth factors I and II, heparin-binding epidermal growth factor, vascular endothelial growth factor, transforming growth factors a and b, and keratinocyte growth factor. Growth factors are known to stimulate fibroblasts, granulation tissue, matrix deposition, angiogenesis, and skin cell maturation. The fibroblasts also produce matrix proteins like collagen types I and III, fibronectin, and tenascin, as well as glycosaminoglycans, which bind growth factors and enhance their activity.[14,15]

The overall safety and lack of rejection reactions combined with the efficacy[16,17] encourages the use of HDS in addition to good wound care practices. In the present paper, the authors describe their experience in the treatment of leg ulcers of various origins with HDS.

Patients and Methods

This was an open, noncomparative, retrospective analysis to assess the use of HDS in the treatment of leg ulcers of various origins when conservative treatment with compression and various local treatments had proved ineffective.



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