Dermagraft®, a bioengineered human dermal equivalent for the treatment of chronic nonhealing diabetic foot ulcer

Chronic nonhealing diabetic foot ulcers are a common medical problem that may precede severe complications such as infection, sepsis and limb loss. Current standard methods of treatment are aimed at removing necrotic debris, controlling infection, and relieving chronic pressure on the wound. Unfortunately, healing rates are poor with standard treatment, averaging 12–20 weeks in clinical trials. A new strategy for the treatment of diabetic foot ulcers has been developed through tissue engineering, allowing the application of healthy living skin cells to assist in the healing process. It is hoped that the living tissue will release appropriate quantities of growth factors, cytokines and other proteins to stimulate the chronic wound bed and accelerate healing. Dermagraft® (Smith & Nephew) is a neonatal-derived bioengineered tissue comprised of dermal fibroblasts. In this article, the structure and behavior of this tissue will be examined, focusing particularly on the randomized clinical trials performed to justify its use in diabetic foot ulcers.

[1]  J. Guilhou,et al.  [Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent]. , 1999, Annales de dermatologie et de venereologie.

[2]  J. Smiell,et al.  Efficacy and Safely of a Topical Gel Formulation of Recombinant Human Platelet-Derived Growth Factor-BB (Becaplermin) in Patients With Chronic Neuropathic Diabetic Ulcers: A phase III randomized placebo-controlled double-blind study , 1998, Diabetes Care.

[3]  J. Mansbridge,et al.  Three-dimensional fibroblast culture implant for the treatment of diabetic foot ulcers: metabolic activity and therapeutic range. , 1998, Tissue engineering.

[4]  David G Armstrong,et al.  Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. , 2001, Diabetes care.

[5]  M. Sabolinski,et al.  A bilayered living skin construct (APLIGRAF®) accelerates complete closure of hard‐to‐heal venous ulcers , 1999, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[6]  J. Ricotta,et al.  Use of Dermagraft, a Cultured Human Dermis, to Treat Diabetic Foot Ulcers , 1996, Diabetes Care.

[7]  J. Mansbridge,et al.  Modification of Fibroblast γ-Interferon Responses by Extracellular Matrix , 2001 .

[8]  D. Steed.  Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group. , 1995, Journal of vascular surgery.

[9]  D. Margolis,et al.  Risk factors for delayed healing of neuropathic diabetic foot ulcers: a pooled analysis. , 2000, Archives of dermatology.

[10]  Jiang,et al.  Enhancement of wound tissue expansion and angiogenesis by matrix-embedded fibroblast (dermagraft), a role of hepatocyte growth factor/scatter factor. , 1998, International journal of molecular medicine.

[11]  L. Lavery,et al.  Reducing Dynamic Foot Pressures in High-Risk Diabetic Subjects With Foot Ulcerations: A comparison of treatments , 1996, Diabetes Care.

[12]  D. Armstrong,et al.  Activity patterns of patients with diabetic foot ulceration: patients with active ulceration may not adhere to a standard pressure off-loading regimen. , 2003, Diabetes care.

[13]  G. Leese,et al.  Blood flow changes in diabetic foot ulcers treated with dermal replacement therapy. , 2002, The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons.

[14]  R. Sibbald,et al.  High bacterial load in asymptomatic diabetic patients with neurotrophic ulcers retards wound healing after application of Dermagraft. , 2001, Ostomy/wound management.

[15]  S. Homer-Vanniasinkam,et al.  Treatment of venous leg ulcers with Dermagraft. , 2004, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[16]  J. Bowker,et al.  Levin and O'Neal's the diabetic foot , 2007 .

[17]  V. M. Yates,et al.  Tissue‐engineered dermal skin grafting in the treatment of ulcerated necrobiosis lipoidica , 2001, Clinical and experimental dermatology.

[18]  W. Eaglstein,et al.  Tissue engineering and the development of Apligraf, a human skin equivalent. , 1997, Cutis.

[19]  Z. Bloomgarden,et al.  American Diabetes Association 60th Scientific Sessions, 2000: the diabetic foot. , 2001, Diabetes care.

[20]  G. Oster,et al.  Potential Economic Benefits of Lower-Extremity Amputation Prevention Strategies in Diabetes , 1998, Diabetes Care.

[21]  W. Marston,et al.  The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. , 2003, Diabetes care.

[22]  G. Naughton,et al.  A metabolically active human dermal replacement for the treatment of diabetic foot ulcers. , 2008, Artificial organs.