The utility of wound debridement has expanded to include the management of all chronic wounds, even in the absence of infection and gross necrosis. Biofilms, metalloproteases on the wound base, and senescent cells at the wound edge irreversibly change the physiologic features of wound healing and contribute to a pathologic, chronic inflammatory environment. The objective of this review is to provide surgeons with a basic understanding of the processes of debridement in the noninfected wound. (J Am Podiatr Med Assoc 100(5): 353–359, 2010)
Introduction: A study of 72 subjects conducted in the European Union and Australia assessed the safety and efficacy of Apligraf (Organogenesis, Inc, Canton, Massachusetts), a bilayered cell therapy composed of living keratinocytes and living fibroblasts in the treatment of non-infected, diabetic foot ulcers (DFU). The design and patient population of this study were similar to a 208-subject United States study (Veves et al., 2001), which led to FDA approval of Apligraf for the treatment of DFU. EU patient outcomes were compared and contrasted to established US-based patient outcome parameters.
Methods: Subjects with a non-infected neuropathic diabetic foot ulcer present for at least two weeks were enrolled in these prospective, multicenter, randomized, controlled, open-label studies that compared Apligraf used in conjunction with standard therapy (sharp debridement, standard wound care, and off-loading) against standard therapy alone.
Results: The design, conduct, and patient populations of the EU and US studies were comparable. Pooling of data was able to be performed because of the similarity and consistency of the two studies. Efficacy and safety results remained consistent across studies independent of mean ulcer duration that was significantly longer in the EU study (21 months, compared to 10 months in the US). Reported adverse events through 12 weeks were comparable across treatment groups in the two studies. Multiple efficacy measures consistently demonstrated superiority of Apligraf treatment over control treated groups in both studies. Combining the data from both studies, 55.2% (80/145) of Apligraf subjects had complete would closure by 12 weeks, compared to 34.3% (46/134) of Control subjects (P = 0.0005; Fisher3s exact test), and Apligraf subjects had a significantly shorter time to complete wound closure (P = 0.0004; log-rank test).
Conclusions: Both the EU and US studies exhibited superior efficacy and comparable safety for subjects treated with Apligraf compared to control treated subjects. The similar outcomes of the two studies provide robust, consistent evidence of the benefit of Apligraf in treating geographically disparate DFU patient populations.
Porcine-derived xenograft biological dressings (PXBDs) are occasionally used to prepare chronic wound beds for definitive closure before split-thickness skin grafts (STSGs). We sought to determine whether PXBD influences rate of STSG take in lower-extremity wounds.
Lower-extremity wounds treated with STSGs were retrospectively reviewed. Patients were included in one of two groups: wound bed preparation with PXBD before STSG or no preparation. Patients were excluded if they received wound bed preparation via another method. Patient demographics, comorbidities, wound history, wound bed preparation, and 30- and 60-day outcomes were collected.
There was no difference in healing outcomes between the PXBD (n = 27) and no preparation (n = 39) groups. At 30- and 60-day follow-up, percentage of STSG take was not significantly different between groups (77.9% versus 79.0%, P30 = .818; 82.2% versus 80.9%, P60 = .422). Mean wound sizes at these follow-up periods were not different (4.4 cm2 versus 5.1 cm2, P30 = .902; 1.2 cm2 versus 1.1 cm2, P60 = .689). The PXBD group had a higher mean ± SD hemoglobin A1c level (8.3 ± 3.5 versus 6.9 ± 1.6; P = .074) and age (64.9 ± 12.8 years versus 56.3 ± 11.9 years; P = .007) versus the no preparation group.
Application of PXBDs for wound bed preparation had no effect on wound healing compared with no wound bed preparation. The two groups varied only by mean age and hemoglobin A1c level. The PXBD may be beneficial, but these results call for randomized controlled trials to determine the true impact of PXBDs on wound healing. In addition, PXBDs may have utility outside of clinically oriented outcomes, and future work should address patient-reported outcomes and pain scores with this adjunct.