C hronic lower-extremity ulcers are estimated to affect approximately 2.5 million to 4.5 million people in the United States.1 This vast clinical problem is seen mostly in the elderly, the fastest growing segment of the US population. Unhealed ulcers cause substantial disability, morbidity, and long-term care costs. In the US, the estimated annual cost of ulcer treatment may be between $1.9 billion and $2.5 billion. These costs include frequent visits to physicians, care provided by visiting nurses, and often hospital admission for the treatment of accompanying cellulitis.2,3 The clinical management of venous ulcers is debatable; however, a better understanding of the physiology has led to development of new treatment modalities. The main therapy has been compression bandages, surgical correction of venous hypertension, or conventional skin grafting techniques. These procedures are costly and require hospitalizations. Frequently, the wound healing associated with these procedures is only temporary.4–6 One study has shown that 49% of venous stasis ulcers treated with skin grafts recur within 3 months of discharge from the hospital.7 Major disadvantages of skin grafting are the creation of a second surgical site and the need for anesthesia and hospitalization. The donor site is often painful postoperatively, and the patient may require pain management. In addition, the donor site can become infected and can result in a keloid or hypertrophic scar. Studies with standard compression therapy alone have shown that patients with venous ulcers will heal about 50% to 60% of the time within 6 months.8,9 Ulcer duration has proven to impact healing. Several studies have shown that there is an inverse relationship between duration and healing.10 There is a need for more effective therapy, especially for patients with ulcers of long duration and those that recur chronically. Thus, a treatment that could reduce healing time would benefit patients and the community. This treatment should heal ulcers more efficiently with less hospitalization and few side effects. Advances in biotechnology over the past few years have given the practitioner more options through the development of new products for the treatment of lower-extremity ulcers. One such product is bilayered extracellular matrix (ECM; OASIS® Wound Matrix, Healthpoint, Ltd., Fort Worth, Tex). This material, approved by the US Food and Drug Administration (FDA) in 1999, is indicated for the management of venous ulcers along with various other indications for wound management. It is composed of small intestinal submucosa derived from porcine intestine. It is created in a multistep process that separates the layers of the small intestine, leaving a thin acellular membrane composed of predominantly collagen and lipids. It also consists of glycosaminoglycans and growth factors, including epidermal growth factor and platelet-derived growth factor among others.11 At the authors’ center, ECM has been used to treat various lower-extremity wounds. In this retrospective study, the authors attempted to determine if ECM with an Unna boot compression dressing was more effective at healing venous stasis ulcers than traditional Unna compression dressing supplemented by a wound drainage controlling agent alone. Materials and Methods Thirty-three randomized outpatients diagnosed with venous insufficiency and venous leg ulcers were recruited to the study. The inclusion criterion was venous leg ulceration based on clinical criteria. Exclusion criteria were clinical signs of infection and patients with other causes of leg ulceration other than venous origin, ie, malignancy, rheumatoid vasculitis, arterial insufficiency, etc. All patients who participated in the study were current patients at the Cabrini Medical Center (CMC) Wound Care Center, were informed of the retrospective study, and provided consent. The patients were divided into 2 groups based on the dressings applied. Group A consisted of 18 patients, and Group B consisted of 15 patients. The average age of the population was 66 years (38–75). Group A was treated with the commercially available ECM and application of a classic Unna boot method of compression. Group B was treated with the classic Unna boot only. The patients were instructed to wear the modality at all times and to keep the treatment modality undisturbed. A dedicated wound care staff at CMC Wound Care Center applied both modalities. Group A received the ECM application followed with a commercially available nonadherent dressing (Adaptic, Johnson & Johnson Wound Management, Somerville, NJ), followed with 0.9% normal saline 4x4 dressing, followed with Unna dressing wrap. Staff applied the wrap material to the extremity in a circumferential manner, starting at the most distal point and applying the wrap proximally in an overlapping manner approximately one-half to two-thirds of the width of the material. Next, a web roll (cast padding) layer was applied in the same fashion. Lastly, an elastic dressing material (3M™ Coban™ Self-Adherent Wrap, 3M Health Care, St Paul, Minn) was applied in the same overlapping manner. The classic Unna boot application consisted of applying a commercial Unna dressing wrap to the extremity in a circumferential manner, starting at the most distal point and applying proximally in an overlapping manner approximately one-half to two-thirds of the material width. Next, a web roll layer was applied in the same overlapping fashion. Lastly, a wrap layer (3M™ Coban™) was applied in the same overlapping fashion. Each week, dressing changes were performed and wound surface areas were measured. The efficacy parameters of the study were 1) the complete healing of the ulcer; 2) tri-weekly wound surface reduction; 3) time to healing; and 4) patient follow up for 12 weeks. The patients visited the outpatient clinic every week. At each outpatient clinic visit, the outer margins of the ulcers were traced for measurement, cleansed with normal saline, and debrided when necessary. After the chart review, all ulcer wound surface reduction was calculated according to the percentage decrease in the area of the ulcer formula. Researchers listed performed the evaluations. Students’ t test was used for statistical analysis of the reported data. Data were expressed as mean ± standard error of mean (±SEM). Results Thirty-three charts were found to have sufficient data and were reviewed. The 2 groups were similar in age and gender. The initial ulcer size was 6.6±1.3 cm2 in Group A and 5.9±0.8 cm2 in Group B. The ulcer duration in weeks was 17.6±6.7 in Group A and 19.4±5.3 in Group B. Lastly, prior ulcer recurrence was 84% in Group A and 87% in Group B (Table 1). None of the patients experienced a serious adverse event related to the study during the trial. At the end of 12 weeks, the complete healing rates were found to be 76.56% (13/18) in Group A and 74.46% (11/15) in Group B. The tri-weekly wound surface reduction (cm2) was 2.78±0.32 for Group A and 2.34±0.21 for Group B (Table 2). The comparison of both groups according to the complete healing rates showed no significant difference (p>0.05). Discussion The morbidity and economic burden associated with venous ulcers have led to a growing interest in the development of new approaches to accelerate healing. In this retrospective study, the authors have shown that ECM does not significantly improve venous ulcer healing compared to standard compression dressing. Although ECM leaves an adequate layer of granulation tissue, is easy to apply, and is well tolerated by patients, the physicians at the CMC Wound Care Center believe that the foundation of venous ulcer treatment includes the control of lower-extremity edema and the maintenance of a more stable compression pressure. Given the data collected by this project and the present body of evidence collected to date, it is recommended that further considerations be made to augment clinicians’ armament to treat venous leg ulcers. The standard of care for patients with venous disease implies following a “minimum” set of parameters and treatment regimens. These standards focus on accurate diagnosis, local wound care, infection control, and the application of compression therapy. The mainstay of therapy has been the relief of venous hypertension by external compression.10,12,13 The traditional Unna boot is a popular and effective form of compression therapy. It is a moist zinc-impregnated bandage and provides both compression and topical treatment.8 Additionally, compression may be applied by re-enforcement of web-role elastic bandage in multiple layers. However, this decision remains with the clinician. Available data has not proved nor disproved the effectiveness of this theory. Fletcher and Sheldon14 reviewed 24 randomized trials and found that compression alone is superior to other treatment modalities without compression. This significant difference was partly explained by the maintenance of a more stable compression pressure. Conversely, the Unna boot does not accommodate changes in the volume of the leg. Another disadvantage is the operator-dependent nature of the compression achieved. In many studies, no clear difference in the effectiveness of different types of compression systems has been shown.9 However, compression therapy has remained the standard therapy.10,12 Extracellular matrix is a new biomaterial taken from porcine small intestine. The sub-mucosa provides strength to the intestine through a complex organization of collagen that forms a fibrous matrix. Extracellular matrix is extracted from the intestine in a manner that removes all cells but leaves the complex matrix intact. It retains the natural composition of matrix molecules, such as collagen (types I, III, IV), glycosaminoglycans (hyaluronic acid, chondroitin sulfate A and B), proteoglycans, and glycoproteins (fibronectin), which are known to have important roles in host tissue repair and remodeling. Benbow11 reported that ECM stimulates healing in noninfected wounds. Prospects to augment compressive therapy could include spray application of living keratinocytes and fibroblasts as biological dressings. For surgical management of venous hypertension to resolve venous reflux, the patient’s vein reflux is treated with endoluminal radiofrequency thermal occlusion, which obliterates the vein. Hydroxyrutosides restore endothelial barrier function. Electrical stimulation has been recently shown in a meta-analysis to provide significant benefit for healing chronic wounds of many etiologies, including venous ulcers, and at this point has the most literature-based support.15–18