Autologous, allogenic and alloplastic materials for bony reconstruction in the cranio-maxillofacial area have many drawbacks thus stimulating the on-going search for new (bio-)materials. Whereas cultivated skin and mucosa are already in clinical routine use in head and neck reconstruction, so far there has been no successful clinical application to the best of our knowledge of periosteum-derived, tissue-engineered bone for augmentation of the edentulous posterior maxilla. In a pilot study, augmentation of the posterior maxilla was carried out using a bone matrix derived from mandibular periosteal cells on a polymer fleece. This paper demonstrates fabrication of the matrix, clinical application, and the histological results in two patients. The results suggest that periosteum-derived osteoblasts on a suitable matrix form lamellar bone within 4 months which allows reliable implant insertion.