In the United States, chronic wounds affect 5.7 million patients and cost health care systems an estimated $20 billion annually.1 Optimal wound care requires understanding the evidence in support of emerging therapies, realizing the cost benefits of these therapies, and knowing when to refer patients to a specialized wound-care center. This article describes the application and benefits of some of the more recent modalities.

Topical growth factor Currently, only one topical growth factor is FDA-approved for clinical use. Regranex Gel contains becaplermin, a recombinant human platelet-derived growth factor. The topical gel is indicated for lower-extremity diabetic neuropathic ulcers that extend into or beyond the subcutaneous tissue and have an adequate blood supply. A black-box warning notes a postmarketing increase in mortality secondary to malignancy in patients who used three or more tubes of Regranex Gel. In clinical trials, increased granulation tissue formation and epithelialization led to cost-effective accelerated healing in patients with lower-limb diabetic neuropathic ulcers and decubitus sores.2 However, Regranex Gel should be used only when the benefits can be expected to outweigh the risks.

Cell-based wound therapies Composed either of dermal components alone or a combination of dermal and epidermal components, bioengineered skin products stimulate the wound-healing process.

Apligraf, or bilayered bioengineered skin substitute (BBSS), consists of living cells and structural proteins. The lower dermal layer combines bovine type-1 collagen and human fibroblasts that produce additional matrix proteins. The upper epidermal layer is formed by stimulating human keratinocytes to multiply and then to differentiate to replicate the architecture of the human epidermis. BBSS does not contain melanocytes; Langerhans cells; macrophages; lymphocytes; or other structures, such as blood vessels, hair follicles, or sweat glands. When placed on a wound, BBSS stimulates the release of cytokines and growth factors into the neighboring tissue, thereby enhancing healing and wound closure. BBSS is indicated for use in venous ulcers of at least 1 month's duration that have not adequately responded to conventional ulcer therapy. This agent is also indicated in combination with conventional care for the treatment of full-thickness neuropathic diabetic foot ulcers of greater than 3 weeks' duration that extend through the dermis but do not involve tendon, muscle, joint capsule, or bone. (Photos of a wound treated with BBSS appear in the online version of this article.) Dermagraft is a cryopreserved human dermal substitute. It is manufactured from human fibroblasts derived from newborn foreskin tissue and composed of an extracellular matrix and a bioabsorbable scaffold.

Dermagraft is indicated for full-thickness diabetic foot ulcers that have lasted longer than 6 weeks and extend through the dermis but do not involve tendon, muscle, joint capsule, or bone. Dermagraft should be used along with standard wound care in patients who have adequate blood supply to the involved foot.

Data show that compared with conventional wound care alone, bioengineered skin products are highly effective in accelerating epithelialization and stimulating the healing of chronic wounds.3,4 Both Apligraf and Dermagraft have been used in hundreds of thousands of patients; have an excellent safety profile; and are covered by Medicare, Medicaid, and several hundred private payers in the United States.5,6 The average annual cost of managing patients with ulcers of longer than 1 year's duration was estimated to be $20,041 per patient treated with BBSS plus compression therapy and $27,493 per patient treated with compression therapy alone.7

Hyperbaric oxygen therapy (HBOT) The premise and support for the use of HBOT stems from evidence that wounds which fail to heal are typically hypoxic.8 Hyperbaric oxygen significantly increases the oxygen saturation of plasma, raising the partial pressure and hence the oxygen available to tissues. HBOT is also thought to stimulate production of growth factors involved in angiogenesis and other mediators of the wound-healing process. Moreover, hyperbaric oxygen has direct and indirect antimicrobial activity.8,9 Treatment generally involves a minimum of 30 sessions during which the patient breathes in 100% oxygen at 2 to 2.5 atmospheres for a total of 90 minutes.

HBOT is recommended for the treatment of diabetic leg wounds with deep soft-tissue infection, osteomyelitis, or gangrene and has reduced the amputation rate in patients with diabetic ulcers.10 In one study, 94% of patients maintained an intact limb at 55 months post-HBOT.11 To date, the FDA has approved seven indications for HBOT in wound care (Table 1).

Subatmospheric wound therapy Significant clinical experience and published research have demonstrated the effectiveness of negative-pressure wound therapy (NPWT), particularly in postsurgical wound-healing complications and in the management of open surgical wounds, amputation sites, and pressure ulcers.12 This approach has led to reduced edema, decreased bacterial load, and promotion of granulation and epithelial closure. In NPWT, the wound is sealed with a gauze or foam dressing and negative pressure is applied to the wound bed via tubing threaded through the dressing. The vacuum may be applied continuously or intermittently, and the dressing is typically changed two to three times a week. Although the cost is not insignificant, numerous studies have shown cost-effectiveness in the treatment of acute and chronic wounds, such as surgical wounds and pressure ulcers.13

Wound-care centers A specialized, multidisciplinary approach to the treatment of chronic wounds has yielded positive outcomes.14 As the incidence of chronic wounds and the associated costs of care have increased substantially over the past decade, the development of specialized wound-care centers has grown exponentially across the country. Wound-care centers offer a great resource for patients with nonhealing and problematic wounds, which include diabetic ulcers, large wounds, wounds that do not decrease in overall size by 50% in a 4-week period, and wounds related to radiation treatment.15 Identifying patients with anticipated healing problems and referring them promptly for advanced wound care has been shown to reduce cost and improve outcomes.15 Woundcare centers are typically staffed by physicians specializing in surgery, emergency medicine, or podiatry; nurses certified in wound, ostomy, and continence care; nonphysician providers; hyperbaric technicians; and support staff. Clinical practice guidelines and evidence-based practice are employed to improve healing rates and ensure quality outcomes, utilizing technology and advanced modalities.15

The initial visit to a wound-care center involves a full assessment to determine the etiology of the wound, its appropriate classification and size, and comorbidities that may impact the patient's ability to heal. Treatment may include wound debridement, specific and diagnostic testing, dressing selection, nutritional support, and patient education. JAAPA

Erich Fogg is program director of the York County Center for Wound Healing and Hyperbaric Medicine, York Hospital, York, Maine. He has indicated no relationships to disclose relating to the content of this article.

Sarah Zarbock, PA-C, department editor

REFERENCES

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