A major challenge for clinicians treating (arterio) venous leg ulcers is to decide between standard therapy and advanced interventions. Here, we developed a simple method to collect human material representative of the ulcer wound bed, which can be used to identify biomarkers for prognostic test development. Superficial surgical debridement was performed using a small vidal curette during the weekly visit to the outpatient clinic. Moist, easily removable debridement material essentially blood free (including necrotic and nonviable slough) was collected from the surface of the ulcer. The amount ranged from 5.5 mg to 78 mg material per ulcer. Seventeen cytokines, chemokines, and growth factors were extracted and analyzed by enzyme-linked immunosorbent assay (concentration range: 0.0005-78 ng/mg total protein). Notably, CXCL8 was by far the most abundant protein present. Inflammatory mediators were more abundant than anti-inflammatory mediators (e.g., interleukin (IL)-10 and transforming growth factor-β1). Bioactivity assays showed chronic wound extracts to be capable of stimulating fibroblast migration in a chemokine-dependent manner and also capable of stimulating healthy cells within skin substitutes to secrete wound healing mediators (CCL2, CXCL1, CXCL8, IL-6) in an IL-1α dependent manner. Collection of debridement tissue enables investigation of the ulcer environment in an easy noninvasive manner that may be suitable for prognostic test development.

Chronic ulcers ((arterio)venous, decubitus, or postoperative) have no tendency to heal within a period of at least 3 months despite optimal therapy according to internationally accepted guidelines. This retrospective study evaluates the safety and efficacy of an autologous, dermal-epidermal skin substitute (SS) for treating ulcers of various origins. Ulcers were treated within 7 Dutch centers over 5 years. Sixty-six ulcers (size: 0.75-150 cm²; duration: 0.25-32 years) with a follow-up time of 24 weeks after a single-skin substitute application were assessed. Wound-bed preparation consisted of vacuum-assisted-closure-therapy (5 days, hospitalized) or application of acellular dermis (5-7 days, outpatient). Time to heal, adverse events, and recurrence 1 year after complete healing were recorded. Complete ulcer healing occurred in 36 of 66 ulcers (55%) at 24 weeks. At that time point, a further 29% of ulcers showed decrease in ulcer size between 50 and 99%. No difference was observed between the hospitalized vs. outpatient treatment with complete healing. There were 32 of 36 healed ulcers that were available for follow-up 1 year after complete closure, of which 27 (84%) were still closed. Only two minor/moderate possibly related adverse events were recorded. This retrospective analysis shows that SS provides a safe and successful treatment for particularly chronic ulcers of various origins.

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