Background:The present study was first to evaluate the material-specific cellular tissue response of patients with head and neck cancer to a nanocrystalline hydroxyapatite bone substitute NanoBone (NB) in comparison with a deproteinized bovine bone matrix Bio-Oss (BO) after implantation into the sinus cavity.Materials and Methods:Eight patients with tumor resection for oral cancer and severely resorbed maxillary bone received materials according to a split mouth design for 6 months. Bone cores were harvested prior to implantation and analyzed histologically and histomorphometrically. Implant survival was followed-up to 2 years after placement.Results:Histologically, NB underwent a higher vascularization and induced significantly more tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated giant cells when compared with BO, which induced mainly mononuclear cells. No significant difference was observed in the extent of new bone formation between both groups. The clinical follow-up showed undisturbed healing of all implants in the BO-group, whereas the loss of one implant was observed in the NB-group.Conclusions:Within its limits, the present study showed for the first time that both material classes evaluated, despite their induction of different cellular tissue reactions, may be useful as augmentation materials for dental and maxillofacial surgical applications, particularly in patients who previously had oral cancer.