## 2 Materials and Methods  
In this trial, full-thickness skin defects were generated paravertebrally in female Gottingen minipigs due to the physiologic concordance to human skin [8; 9]. The animals were provided from Ellegaard Gottingen Minipigs A/S, Dalmose, Denmark, aged 39 weeks (\(\pm\)12 days) and weighed 22.6 kg (\(\pm\)1.4 kg). Animals were treated according to the German Law on the Protection of Animals, and the study was performed with permission from the local Animal Welfare Committee (approval code AT 1/12).  
On the first day of the study, the Gottingen minipigs were anesthetized and their backs were shaved, surgically disinfected in a standardized manner and the outline of the wounds was tattooed. Eighteen full-thickness skin defects (2.0 cm diameter, 0.6 cm depth) were created, and a single dressing was applied with either a crosslinked biomatrix (\(n=6\)) or a non-crosslinked biomatrix (\(n=6\)). Control wounds remained untreated (\(n=6\)). The crosslinked biomatrix (Bilayered Integra(r) by Integra(r) by Integra Life Sciences Corporation, Plainsboro, NJ, USA) is an acellular crosslinked collagen type I and chondro-6-sulphate based bilayered biomatrix with a polysiloxane polymer layer. It is produced from bovine tendon and shark glycosaminoglycan. The silicone was left on the wound for seven days. The non-crosslinked biomatrix (Matriderm(r) 1.00 mm by Dr. Suwelack Skin & Health Care AG, Billerbeck, Germany) is based on a compound from lyophilized collagen type I, III, V and \(\alpha\)-elastin in a decellularized non-crosslinked biomatrix of bovine origin. The wound dressings were applied to the wounds in a randomized manner with a standardized separation distance of 6.0 cm sealed with adhesive foil (Smith & Nephew Orthopaedics GmbH, Tuttlingen, Germany) to protect the implants, avoid cross-contamination and prevent bacterial contamination. Additionally, the minipigs wore customized minipig jackets (Ellegaard Minipig Jacket Large Full Body, Lomir Biomedical Inc., Notre Dame de LIlle Perrot, QC, Canada), as previously described [10; 11; 12; 13].  
Bandage renewal and photographic documentation were performed every second day using a digital camera with a tripod to determine the exact distance. The evaluation was carried out plainmetrically by importing the photos into Adobe Photoshop (Adobe Systems Inc., San Jose, CA, USA) and calculating the percentage of epithelialization during the study period of 21 days [14]. After 20 days, original circular wound areas were excised, and samples were processed for histopathological evaluation. Histological slices were stained with hematoxylin and eosin to analyze the resulting neodermal thickness and cell density. The thickness of the neoepidermis was determined repetitively from the basal layer to the stratum corneum of the epidermis, and the number of keratinocytes was quantified within a rectangular area of 100 \(\times\) 50 \(\upmu\)m (5 mm\({}^{2}\)), both in three different sections with an interval of 100 \(\upmu\)m. Pictures were taken with a digital microscope camera (AxioCam ERc 5s, Carl Zeiss Microscopy GmbH, Jena, Germany) connected to a Zeiss microscope (Axio Observer.Z1, Carl Zeiss Microscopy GmbH, Jena, Germany) with the ZEN blue edition (2011) microscopy software (Carl Zeiss Microscopy GmbH, Jena, Germany). The study was carried out after approval of the local Animal Welfare Committee in accordance with the German Animal Protection Act. Statistical evaluation was performed using SPSS software version 20.0. The results were analyzed with the Wilcoxon rank-sum test with a defined \(p\)-value \(\leq\) 0.05.