Bone loss in the oral and maxillofacial region caused by trauma, tumors, congenital disorders, or degenerative diseases is a health care problem worldwide. To restore (reconstruct) these bone defects, human or animal bone grafts or alloplastic (synthetic) materials have been used. However, several disadvantages are associated with bone graft transplantation, such as limited bone volume, donor-site morbidity, surgical and immune rejection risks, and lack of osseo-integration. Bone tissue engineering is emerging as a valid alternative to treat bone defects allowing the regeneration of lost bony tissue, thereby recovering its functionality. During the last decades, the increasing aged population worldwide has also raised the prevalence of maxillary atrophy. Maxillary sinus floor elevation (MSFE) has become a standard surgical procedure to overcome the reduced amount of bone, thus enabling the placement of dental implants. MSFE aims to increase the bone height in the posterior maxilla, by elevating the Schneiderian membrane and placing the graft material into the surgically created space in the maxillary sinus floor. Importantly, oral bone regeneration during MSFE offers a unique human clinical model in which new cell-based bone tissue engineering applications might be investigated, since biopsies can be taken after MSFE before a dental implant placement and analyzed at the cellular level. New approaches in oral bone regeneration are focusing on cells, growth factors, and biomaterials. Recently, adipose tissue has become interesting as an abundant source of mesenchymal stem cells, which might be applied immediately after isolation to the patient allowing a one-step surgical procedure, thereby avoiding expensive cell culture procedures and another surgical operation. In this new cell-based tissue engineering approach, stem cells are combined with an osteoconductive scaffold and growth factors, and applied immediately to the patient. In this review, MSFE is discussed as a valid model to test bone tissue engineering approaches, such as the one-step surgical procedure. This procedure might be applied in other regenerative medicine applications as well.