## 3 Results
### Histological Analysis  
Histological analysis of the untreated control wounds showed a mean neoepidermal thickness of 22.50 \(\upmu\)m (range of 12.52-39.57 \(\upmu\)m). For the collagen-elastin matrix-treated group, a mean thickness of 31.01 \(\upmu\)m (range of 23.03-61.45 \(\upmu\)m, \(p\) = 0.0015) was found. Higher values were found for the mean neoepidermal thickness of wounds treated with the collagen-gelatin scaffold embedded with rhGDF-5. For dressings applied only once, these values were 26.02 \(\upmu\)m (range of 16.71-64.85 \(\upmu\)m, \(p\) = 0.0405) for the 30 g/m\({}^{2}\) scaffold with 100 ng rhGDF-5, 34.01 \(\upmu\)m (range of 21.65-57.20 \(\upmu\)m, \(p\) = 0.0008) for the 75 g/m\({}^{2}\) scaffold with 500 ng rhGDF-5, 44.97 \(\upmu\)m (range of 20.13-76.35 \(\upmu\)m, \(p\) < 0.0001) for the 150 g/m\({}^{2}\) scaffold with 1000 ng rhGDF-5, and 42.80 \(\upmu\)m (range of 16.20-76.44 \(\upmu\)m, \(p\) < 0.0001) for the 90 g/m\({}^{2}\) scaffold with 5000 ng rhGDF-5. For dressings applied multiple times, higher values of thickness were seen compared to the single-treated groups. These values were 48.47 \(\upmu\)m (range of 32.54-100.91 \(\upmu\)m, \(p\) < 0.0001) for the 30 g/m\({}^{2}\) scaffold with 100 ng rhGDF-5, 61.72 \(\upmu\)m (range of 27.75-98.40 \(\upmu\)m, \(p\) < 0.0001) for the 75 g/m\({}^{2}\) scaffold with 500 ng rhGDF-5, 61.27 \(\upmu\)m (range of 40.37-72.23 \(\upmu\)m, \(p\) < 0.0001) for the 150 g/m\({}^{2}\) scaffold with 1000 ng rhGDF-5, and 48.13 \(\upmu\)m (range of 21.60-68.06 \(\upmu\)m, \(p\) < 0.0001) for the 90 g/m\({}^{2}\) scaffold with 5000 ng rhGDF-5 (Figure 3). Next, the mean epidermal cell density was determined from the neoepidermis. For untreated controls, the cell density amounted to 41.00 cells (range of 22.00-68.00 cells) (Figure 4). This value was higher for the collagen-elastin matrix-treated groups compared to the control ones and amounted to 84.50 cells (range of 79.00-106.00 cells, \(p\) = 0.0002). For the composite biomaterial groups with dressings applied only once to the skin defects, higher values of cell density were found compared to the control group, but lower than those of the collagen-elastin matrix groups. Statistically significant results were obtained, with 69.50 cells (range of 54.00-89.00 cells, \(p\) = 0.0132) for the 150 g/m\({}^{2}\) scaffold with 1000 ng rhGDF-5, and 64.00 cells (range of 45.00-69.00 cells, \(p\) = 0.0229) for the 90 g/m\({}^{2}\) scaffold with 5000 ng rhGDF-5 (Figure 4). However, for the groups with dressings applied multiple times to the skin defects, a higher cell density was seen compared to all other conditions. These values were 90.50 cells (range of 55.00-154.00 cells, \(p\) = 0.0118) for the 30 g/m\({}^{2}\) scaffold with 100 ng rhGDF-5, 93.50 cells (range of 38.00-135.00 cells, \(p\) = 0.0174) for the 75 g/m\({}^{2}\) scaffold with 500 ng rhGDF-5, 87.00 cells (range of 61.00-104.00 cells, \(p\) = 0.0019) for the 150 g/m\({}^{2}\) scaffold with 1000 ng rhGDF-5, and 72.50 cells (range of 38.00-110.00 cells, \(p\) = 0.0374) for the 90 g/m\({}^{2}\) scaffold with 5000 ng rhGDF-5 (Figure 4). Figure 3: Histological analysis of the epidermal thickness. The epidermal thickness was histologically evaluated in micrometers by repetitive measurements from the stratum basale to the stratum corneum in three different sections per sample, with an interval of 100 \(\upmu\)m.  
In comparison to untreated wounds, all examined wound dressing conditions functioning as skin substitutes accelerated dermal wound healing by reducing the time required to close the wound completely, to thicken the neodermal tissue, and to increase the epidermal cell density. Based on the results of the multiple-application groups, the local application of higher rhGDF-5 concentrations (100, 500, and 1000 ng) resulted in better wound healing compared to lower concentrations, indicating an rhGDF-5 dose-dependent relationship with wound healing. However, 5000 ng of rhGDF-5 did not further improve wound healing.