With the advancement of tissue engineering an alternative approach was developed: the full-thickness engineered oral mucosa. Full-thickness engineered oral mucosa is a better simulation of the in vivo situation because they take the anatomical structure of native oral mucosa into account. Problems, such as tissue shortage and donor site morbidity, do not occur when using full-thickness engineered oral mucosa.
The main goal when producing full-thickness engineered oral mucosa is to make it resemble normal oral mucosa as much as possible. This is achieved by using a combination of different cell types and scaffolds. 
* Lamina propria: is mimicked by seeding oral fibroblasts, producing extracellular matrix, into a biocompatible (porous) scaffold and culturing them in a fibroblast differentiation medium.
* Basement membrane: containing type IV collagen, laminin, fibronectin and integrins. Ideally, the basement membrane must contain a lamina lucida and a lamina densa.
* Stratified squamous epithelium: is simulated by oral keratinocytes cultured in a medium containing keratinocyte growth factors such as the epidermal growth factor (EGF).
To obtain the best results, the type and origin of the fibroblasts and keratinocytes used in oral mucosa tissue engineering are important factors to hold into account. Fibroblasts are usually taken from the dermis of the skin or oral mucosa. Kertinocytes can be isolated from different areas of the oral cavity (such as the palate or gingiva). It is important that the fibroblasts and keratinocytes are used in the earliest stage possible as the function of these cells decreases with time. The transplanted keratinocytes and fibroblasts should adapt to their new environment and adopt their function. There is a risk of losing the transplanted tissue if the cells do not adapt properly. This adaptation goes more smoothly when the donor tissue cells resemble the cells of the native tissue.