Comparison of Efficacy among Three Dermal Substitutes in the Management of Critical Lower-Limb Wounds: The Largest Biases-Reduced Single-Center Retrospective Cohort Study in Literature

Background and objectives: The skin recently became the main focus of regenerative medicine and, in this context, skin substitutes are fully entering into the plastic surgeon's armamentarium. Among the various types of skin substitutes, dermal substitutes (DSs) are the most used. Our study aims to retrospectively compare three renowned and extremely similar DS in the management of critical lower limb wounds in the largest cohort analysis currently present in literature. Materials and Methods: We followed a strict protocol of application and evaluation of the DS for each patient and wound and, after a meticulous bias reduction process, we compared final outcomes in terms of efficacy and speed in achieving the defect coverage. Results: Among patients who did not receive a skin graft after the DS, we registered a wound healed surface of 50% for Pelnac, 52% for Integra, and 19% for Nevelia, after 30 days from the external silicon layer removal; among those who received a skin graft after the DS, we observed a significantly lower mean percentage of graft take after 7 days with Pelnac (53%) compared to Integra and Nevelia (92% and 80%, respectively). The overall percentage of wound healed surface obtained after 30 days from the external silicon sheet removal, either with or without skin graft, was 71% for Pelnac, 63% for Integra and 63% for Nevelia. We also ran a sub-group analysis only including grafted wounds with a negative microbiological test and the mean percentage of graft take was similar this time. Eventually, we assessed the influence of the wound's "chronicity" on its healing, comparing the mean graft take only in "acute" wounds who received a skin graft and it resulted 63% for Pelnac, 91% for Integra and 75% for Nevelia. Conclusions: Integra demonstrates the highest rate of skin graft viability and the highest rate of skin graft takes after 7 days. Pelnac shows the quickest induction of secondary healing in acute wounds. Nevelia is not different from Integra and shows a superior graft take compared to Pelnac, but features the lowest secondary healing induction rate. No differences exist between the three DSs in terms of wound healing after 30 days from the skin graft or from the removal of the external silicon layer.