The aim of this study was to regenerate the pneumatic air cells and their gas exchange function in the poorly developed mastoid cavities of patients with chronic otitis media.<br>Five patients with severe chronic otitis media whose mastoid air cells were poorly developed took part in this clinical trial. Four of 5 patients underwent staged operation of tympanoplasty.<br>Honeycomb-like structures made of hydroxyapatite (HA) coated with collagen was used as a framework for artificial pneumatic bones. At the first stage of tympanoplasty, collagen-coated HA was implanted into the newly opened mastoid cavity and was fixed by fibrin glue. After the first operation, recovery of mastoid aeration and regeneration of the pneumatic air cells of the newly opened mastoid cavity were assessed on CT scan images. In 4 of 5 cases, aeration was recovered. The pneumatic air cells were regenerated in 3 cases.<br>This study demonstrated that the mastoid air cells could be regenerated with implanted HA in the newly opened mastoid cavity. This tissue engineering method may be a possible treatment for intractable otitis media because it can recover the gas exchange function.