Background and Aim: It is long known that patients with insufficientmaxillary bone height might need maxillary sinus floor elevation (MSFE)prior to the placement of dental implant. Currently, the bone substitutesare used as an alternative as the ‘gold standard’ (i.e., as the autologousbone). However, the bone substitutes only allow the osteoconduction,since viable osteogenic cells are lacking. In the recent years, cell-basedbone tissue engineering has been introduced as a promising treatmentoption to improve the bone forming capacity of bone substitutes.Methods: In a government-sponsored phase I trial, we assessed thefeasibility, safety and efficacy of combining a calcium phosphate (CaP)as a bone substitute using freshly isolated adipose stem cells during aone-step surgical procedure for MSFE. In this line, to avoid costly stemcell expansions and a second intervention, the osteoinductive carriers(i.e., CaP seeded with the freshly isolated stromal vascular fraction ofadipose tissue) were generated in an intra-operative procedure in theOR-complex within hours. Furthermore, a ‘split-mouth design’ (withonly CaP scaffold at the contralateral control side) was applied to allowefficacy evaluation, wherever possible. At regular intervals during followup,adverse events were monitored, and clinical, X-ray, and Cone-beamCT data were collected. After six months, biopsies were obtained duringthe placement of dental implant, which were evaluated for the bone formation by histomorphometry and μCT.Results: In this phase I trial, we included 10 patients. All patientsuneventfully underwent an MSFE procedure and no adverse effectswere reported during 3.5-year follow-up. Bone as well as an osteoidpercentage were higher in bone biopsies taken from study sides thanthe control sides throughout the complete biopsies, suggesting that boneformation does not only occur from the pre-existing sinus floor, and thatadipose stem cells may stimulate bone formation.Conclusion: For the first time, this present study demonstrated thefeasibility, safety and potential efficacy of freshly isolated adipose stemcells with a calcium phosphate for MSFE. Based on these findings, thismodality provides the first step towards a novel treatment concept thatmight offer the broad potential for cell-based regenerative medicineapplications.