Large full-thickness skin defects resulting from burns, soft tissue trauma, congenital giant nevi, tumour resection, and disease leading to skin necrosis, represent a significant and common clinical problem worldwide. This problem is far from being solved. The main challenge encountered is that most autologous skin grafting techniques are based on transplanting split-thickness skin (the today’s gold standard). Split-thickness skin contains all of the epidermis, but only remnants of the dermis. This lack of dermal tissue, frequently leads to significant scarring. Consequently, a true dermal substitute is required, which instantly exerts the cell-instructive properties of a neo-dermis. The partners of EuroSkinGraft can now offer 2 dermal substitutes, Novomaix and denovoDerm, plus the dermo-epidermal skin substitute denovoSkin. The development of all 3 substitutes was significantly supported by the FP6-program (EuroSTEC). The envisaged clinical studies are aiming strictly at a one-step surgical procedure (instead of the common two-step procedure, using Integra Artificial Skin).This is to be reached with the following protocol:Clinical application of Novomaix1. Experimental arm 1: split-thickness skin on Novomaix applied on full-thickness wounds2. Reference arm 1: split-thickness skin applied directly on the wound bedClinical application of denovoDerm1. Experimental arm 1: split-thickness skin on denovoDerm applied on full-thickness wounds2. Reference arm 1: split-thickness skin applied directly on the wound bedClinical application of denovoSkin1. Experimental arm 1: denovoSkin applied on full-thickness wounds2. Reference arm 1: split-thickness skin applied directly on the wound bedThe strength of this project lies in: the high degree to which real regenerative medicine is translated into the clinic, the innovative and highly functional character of the 3 products to be tested, the central contribution of the 3 SMEs, and the excellence of the 3 clinics.