Optimizing the generation of large transplantable dermo-epidermal skin replacements is dependent on a three-dimensional matrix that supports the biological function of skin cells and provides mechanical properties to allow for surgery. Until now, collagen type I hydrogels promise the best biological functionality but their mechanical weakness and tendency to contract and degrade do not allow for the generation of large transplants. We have proven that by plastic compression, collagen hydrogels can acquire mechanical and biological stability, while maintaining excellent biological functions. Cultured dermo-epidermal skin grafts based on compressed collagen hydrogels can be handled easily in clinically relevant sizes, do degrade at an appropriate rate, and give rise to near normal homeostatic skin (Braziulis 2012).