Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: a new paradigm in wound healing.

HYPOTHESIS In patients with diabetic foot and pressure ulcers, early intervention with biological therapy will either halt progression or result in rapid healing of these chronic wounds. DESIGN In a prospective nonrandomized case series, 23 consecutive patients were treated with human skin equivalent (HSE) after excisional debridement of their wounds. SETTING A single university teaching hospital and tertiary care center. PATIENTS AND METHODS Twenty-three consecutive patients with a total of 41 wounds (1.0-7.5 cm in diameter) were treated with placement of HSE after sharp excisional debridement. All patients with pressure ulcers received alternating air therapy with zero-pressure alternating air mattresses. MAIN OUTCOME MEASURE Time to 100% healing, as defined by full epithelialization of the wound and by no drainage from the site. RESULTS Seven of 10 patients with diabetic foot ulcers had complete healing of all wounds. In these patients 17 of 20 wounds healed in an average of 42 days. Seven of 13 patients with pressure ulcers had complete healing of all wounds. In patients with pressure ulcers, 13 of 21 wounds healed in an average of 29 days. All wounds that did not heal in this series occurred in patients who had an additional stage IV ulcer or a wound with exposed bone. Twenty-nine of 30 wounds that healed did so after a single application of the HSE. CONCLUSIONS In diabetic ulcers and pressure ulcers of various durations, the application of HSE with the surgical principles used in a traditional skin graft is successful in producing healing. The high success rate with complete closure in these various types of wounds suggests that HSE may function as a reservoir of growth factors that also stimulate wound contraction and epithelialization. If a wound has not fully healed after 6 weeks, a second application of HSE should be used. If the wound is not healing, an occult infection is the likely cause. All nonischemic diabetic foot and pressure ulcers that are identified and treated early with aggressive therapy (including antibiotics, off-loading of pressure, and biological therapy) will not progress.

[1]  W. Scheckler,et al.  Infections and infection control among residents of eight rural Wisconsin nursing homes. , 1986, Archives of internal medicine.

[2]  B L Moody,et al.  Impact of staff education on pressure sore development in elderly hospitalized patients. , 1988, Archives of internal medicine.

[3]  P. Skorga,et al.  Pressure ulcer prevalence in two general hospitals. , 1989, Decubitus.

[4]  M. Auletta,et al.  Cultured skin as a 'smart material' for healing wounds: experience in venous ulcers. , 1996, Biomaterials.

[5]  F. Logerfo,et al.  Vascular disease of the lower extremities in diabetes mellitus. , 1996, Endocrinology and metabolism clinics of North America.

[6]  M. Mohler,et al.  A review of nonclinical toxicology studies of becaplermin (rhPDGF-BB). , 1998, American journal of surgery.

[7]  D. Steed Foundations of good ulcer care. , 1998, American journal of surgery.

[8]  R. Allman,et al.  Pressure ulcer prevalence, incidence, risk factors, and impact. , 1997, Clinics in geriatric medicine.

[9]  T. Rönnemaa,et al.  Healing of chronic leg ulcers in diabetic necrobiosis lipoidica with local granulocyte-macrophage colony stimulating factor treatment. , 1999, Journal of diabetes and its complications.

[10]  E. LeGrand Preclinical promise of becaplermin (rhPDGF-BB) in wound healing. , 1998, American journal of surgery.

[11]  D. Margolis,et al.  Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. , 1998, Archives of dermatology.

[12]  J. Zieske,et al.  Basement membrane assembly and differentiation of cultured corneal cells: importance of culture environment and endothelial cell interaction. , 1994, Experimental cell research.

[13]  S. Kaplan,et al.  Foot infections in diabetic patients. Decision and cost-effectiveness analyses. , 1995, JAMA.

[14]  Pase Mn Pressure relief devices, risk factors, and development of pressure ulcers in elderly patients with limited mobility. , 1994 .

[15]  D Bergqvist,et al.  Chronic leg ulcers: an underestimated problem in primary health care among elderly patients. , 1991, Journal of epidemiology and community health.

[16]  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.

[17]  G. Reiber,et al.  Lower extremity foot ulcers and amputations in diabetes , 1995 .

[18]  A. Zabernigg,et al.  Recombinant human granulocyte‐macrophage colony‐stimulating factor applied locally in low doses enhances healing and prevents recurrence of chronic venous ulcers , 1999, International journal of dermatology.

[19]  J. Burke SKIN : THE FIRST TISSUE-ENGINEERED PRODUCTS , 1999 .

[20]  S. Berceli,et al.  Efficacy of dorsal pedal artery bypass in limb salvage for ischemic heel ulcers. , 1999, Journal of vascular surgery.

[21]  N. Parenteau,et al.  Epidermis generated in vitro: practical considerations and applications , 1991, Journal of cellular biochemistry.

[22]  A. Falabella,et al.  The use of tissue-engineered skin (Apligraf) to treat a newborn with epidermolysis bullosa. , 1999, Archives of dermatology.

[23]  R. Allman,et al.  Pressure ulcers among the elderly. , 1989, The New England journal of medicine.

[24]  D. Steed,et al.  Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic Ulcer Study Group. , 1996, Journal of the American College of Surgeons.

[25]  R. Kirsner,et al.  Behavior of tissue-engineered skin: a comparison of a living skin equivalent, autograft, and occlusive dressing in human donor sites. , 1999, Archives of dermatology.

[26]  A. Shamseddine,et al.  Pressure ulcer accelerated healing with local injections of granulocyte macrophage-colony stimulating factor. , 1997, The Journal of infection.

[27]  C. Nathan,et al.  Secretory products of macrophages. , 1987, The Journal of clinical investigation.

[28]  C. Aniceto,et al.  Double-blind randomized placebo-controlled trial of the use of granulocyte-macrophage colony-stimulating factor in chronic leg ulcers. , 1997, American journal of surgery.

[29]  F. Arnold,et al.  Granulocyte monocyte-colony stimulating factor as an agent for wound healing. , 1995, Journal of wound care.

[30]  J. Maklebust Pressure ulcer assessment. , 1997, Clinics in geriatric medicine.

[31]  Definitions and guidelines for assessment of wounds and evaluation of healing , 2002 .

[32]  Thomas A. Mustoe, MD, FACS,et al.  Granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor: differential action on incisional wound healing. , 1994, Surgery.

[33]  W. Eaglstein,et al.  A Composite Skin Substitute (Graftskin) for Surgical Wounds: A Clinical Experience , 1995, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[34]  E Bell,et al.  Recipes for reconstituting skin. , 1991, Journal of biomechanical engineering.

[35]  J N Morris,et al.  The epidemiology and natural history of pressure ulcers in elderly nursing home residents. , 1990, JAMA.

[36]  J. Smiell Clinical safety of becaplermin (rhPDGF-BB) gel , 1998 .

[37]  V. Gahtan,et al.  What is the Paradigm: Hospital or Home Health Care for Pressure Ulcers ? , 1999, The American surgeon.

[38]  R. Allman OUtcomes in prospective studies and clinical trials. , 1995, Advances in wound care : the journal for prevention and healing.

[39]  C. Goodwin,et al.  Burn Wound Infections: Current Status , 1998, World Journal of Surgery.

[40]  G. Reiber,et al.  Pathways to Diabetic Limb Amputation: Basis for Prevention , 1990, Diabetes Care.

[41]  F. Logerfo,et al.  Current concepts. Vascular and microvascular disease of the foot in diabetes. Implications for foot care. , 1984, The New England journal of medicine.

[42]  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.

[43]  E. Mostow Diagnosis and classification of chronic wounds. , 1994, Clinics in dermatology.

[44]  Diabetes and peripheral vascular disease. , 1999, Journal of vascular surgery.