Abstract: Background: Cymetra™ is a micronized, injectable form of AlloDerm® (LifeCell Corporation, Branchberg, New Jersey), an allogeneic dermal matrix product developed as a filler substance for cosmetic use. Recently, Cymetra has been reported to be effective in the healing of recalcitrant sinus tracts in two patients. Objective: The objective of the authors’ study was to evaluate the safety and efficacy of Cymetra as an adjuvant in the treatment of a variety of chronic wounds. Methods: A retrospective chart review was performed for patients who were treated with Cymetra at the CURE Wound Care Center at the University of Miami, Miami, Florida. Results: Patients with various types of chronic ulcers, including pyoderma gangrenosum, eosinophilic fasciitis, chronic pressure ulcers, post-operative ulcers, venous insufficiency ulcers, and livedo vasculitis, were treated with Cymetra injections. All patients had refractory disease and failed to respond to prior treatments, which included Apligraf® (Organogenesis, Canton, Massachusetts), Dermagraft (Smith & Nephew, Largo, Florida), V.A.C.® Therapy™ (KCI Inc., San Antonio, Texas), compression, etanercept, mycophenolate mofetil, prednisone, infliximab, cyclosporine, antibiotics, debridement, intralesional triamcinolone acetonide, and granulocyte/macrophage colony-stimulating factor (GMCSF). Of the 13 patients treated with Cymetra, nine patients’ ulcers (69%) healed completely. Conclusions: Cymetra was well tolerated, and the majority of patients achieved complete healing of their ulcers after treatment.

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hronic wounds are caused by a variety of etiologies, including diabetic neuropathy, venous and/or arterial insufficiency, and prolonged pressure.¹ In addition to significant morbidity and both financial and emotional costs, chronic wounds have been associated with an increased risk of osteomyelitis and limb amputation and increased mortality.² At present, despite addressing the underlying pathophysiology of the wound and employing adjuvant therapies, such as growth factors and tissue-engineered skin, a need exists for additional options in the therapeutic arsenal. In this article, the authors report their experience with Cymetra® (LifeCell Corporation, Branchberg, New Jersey) as an adjuvant in the treatment of a variety of chronic wounds.
       Cymetra is a micronized, decellularized dermal matrix product developed as a filler substance for cosmetic use. Effective enhancement of aging lips with its use has been reported.³ Cymetra is approved by the US Food and Drug Administration (FDA) as a human tissue for transplantation for the repair or replacement of damaged or inadequate integumental tissues. It is an injectable, micronized form of AlloDerm® (LifeCell Corporation), a nonantigenic, allogeneic, acellular dermal matrix with an intact basement membrane. Cymetra has shown excellent tissue biocompatibility, a low rate of resorption, and no tissue reactivity.⁴ Recently, it has been reported to be an effective adjuvant therapy in two patients with recalcitrant sinus tracts.⁵ Based on these findings, the authors hypothesize that injection of Cymetra into a wound or ulcer may similarly expedite healing, leading to wound closure. In this article, the authors report results of off-label use of Cymetra in 13 patients with refractory ulcers.

Methods

       All patients who received Cymetra were identified from the CURE Wound Care Center at the University of Miami, Miami, Florida. A total of 13 patients were treated. A retrospective chart review of these 13 patients was performed, extracting data on patient demographics, comorbidities, ulcer history, prior treatments, and response to Cymetra.

Results

       Patients. Thirteen patients (9 women and 4 men) were identified. Their mean age at treatment onset was 68 years. Wound types were pyoderma gangrenosum (PG) (6), pressure ulcer (2), post-operative ulcer (2), venous ulcer (1), eosinophilic fasciitis (1), and livedo vasculitis ulcer (1). The ulcers had a median size of 2.4cm2 prior to treatment. The mean wound duration prior to treatment was 6.3 months with a standard deviation of +/- 6.25 months.
       Treatment. Prior to treatment with Cymetra, all 13 wounds received multiple therapies, including compression, occlusive dressings, topical antibiotics and steroids, and skin grafting with autologous or tissue-engineered skin (Table 1). The patients also received systemic medications, such as antibiotics, steroids, and etanercept. Cymetra either was added to or replaced some of the patients’ previous wound care regimen.
       Cymetra was prepared according to the directions from LifeCell Corporation: 330mg of the dehydrated product was rehydrated with one-percent lidocaine in a syringe prior to instillation with an 18-gauge needle. Patients received 1–4mL of Cymetra at dosing intervals ranging from weekly to monthly, depending on ulcer size and response to therapy. Patients with ulcers having maximum diameters of less than 2cm were given an initial injection of 1cc. This dose was maintained or increased according to response. In some cases, other wound therapies were continued in combination with Cymetra treatment, including routine dressing changes, adequate debridement, infection control, compression therapy, and offloading. All other wound treatments used are listed in Table 1.

Table 1

       Ulcer response to Cymetra. Ulcer response to Cymetra is summarized in Table 2. Nine of the 13 patients’ ulcers healed after Cymetra treatment. In eight of the nine patients, the ulcers remained healed for at least three months; the ulcer in patient 11 with peristomal PG reopened after six months and was successfully retreated with conservative wound care. The mean time to healing in the nine patients successfully treated with Cymetra was 3.7 months. Four patients’ ulcers failed to heal. The etiologies of the four nonhealing ulcers were pressure (2), eosinophilic fasciitis (1), and a stump ulcer (1). No adverse effects of Cymetra treatments were observed or reported.

Table 2

Discussion

       Chronic wounds affect more than 6.5 million patients each year and cause significant morbidity and impaired quality of life.⁶ Diabetes, venous or arterial insufficiency, and chronic pressure are the most common etiologies of poorly healing wounds in the US. Approximately 10 percent of leg ulcers are due to atypical causes including inflammatory conditions, such as PG, which can cause refractory ulcers.⁷
       During the past decade, biologically active wound interventions, such as therapeutic growth factor proteins and tissue-engineered products, have become available. In 1997, recombinant human platelet-derived growth factor-BB (rhPDGF-BB, becaplermin) became the first therapeutic growth factor to receive FDA approval for healing chronic wounds.⁸ Similarly, tissue-engineered products, such as Apligraf® (Organogenesis, Canton, Massachusetts) and Dermagraft (Smith & Nephew, Largo, Florida), have been shown to stimulate healing, presumably through the production of growth factors in the wound bed and by providing a framework for the ingrowth of cells.⁹
       Cymetra is a micronized form of AlloDerm, an allogeneic acellular dermal matrix. AlloDerm provides a three-dimensional collagen scaffold that is likely to promote cellular migration and tissue integration. Over time, this matrix is repopulated, and fibroblast infiltration has been confirmed by histology within one month.¹⁰ Moreover, its biologic nature provides AlloDerm less inclination toward infection, erosion, and rejection when compared with synthetic tissue replacement materials. In addition to serving as a filler for cosmetic use, there are recent reports suggesting the utility of AlloDerm to repair meningomyeloceles during neurosurgical reconstructions, increase gingival thickness in patients with buccal recession defects, and repair abdominal wall hernias.^11–13
       Cymetra is the first available injectable dermal matrix. Cymetra maintains the ultrastructure of the dermis yet easily passes through an 18-gauge needle. These properties lend Cymetra significant advantages in ulcers that are deep or undermined and in sinus tracts. As a promoter of healing in recalcitrant sinus tracts, Cymetra has been recently reported in two patients, one of which had a sinus tract complicated by PG. Clinical studies to date describe no allergic or immunologic reactions to Cymetra.
       In this article, the authors report the success of Cymetra in the treatment of chronic wounds. The authors treated 13 patients suffering from chronic ulcers with injections of Cymetra. The ulcers in nine of the 13 patients (69%) healed. These results are similar to those reported by Embil, et al., with the off-label use of becaplermin in which 57.5 percent of patients achieved complete healing of lower-extremity ulcers and also similar to the report by Harrison-Balestra, et al., in which 64 percent of ulcers healed with becaplermin.^14,15 Although Patient 2 failed to heal, the wound showed a marked increase in granulation tissue and was prepared for the placement of V.A.C.® Therapy™ (KCI Inc., San Antonio, Texas). Similarly, there was an increase in granulation tissue in the stump ulcer of Patient 5, and she subsequently underwent a split-thickness skin graft. All six of the patients with PG achieved complete healing after adjuvant therapy with Cymetra.

Conclusion

       The authors found Cymetra to be an effective adjunct for refractory ulcers. In this retrospective series, Cymetra as an adjuvant to ulcer care was a safe addition and effective in healing a variety of ulcers. These preliminary findings suggest that this treatment may be rationally employed with other wound treatment modalities, such as V.A.C. Therapy, growth-factor protein gels, and tissue-engineered dermal replacements. Controlled studies would be useful to more fully determine the efficacy of Cymetra, its duration of effect, and optimize its conditions of use.