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Saddle nose and septal perforations are among the most surgically challenging situations in nasal reconstruction. They require a significant volume of autologous graft and a complex surgical procedure. The aim of this study was to evaluate the biocompatibility of the biphasic calcium phosphate implant in the nasal septum and its ability to replace septal skeleton with unilateral or bilateral exposure.Thirty sheep underwent anterior nasal septum perforation. Only 20 septa were repaired with the implant exposed to nasal content on bilateral (group 2) and unilateral (group 3) sides. After 45 days of spontaneous cicatrization, the surface of new airway mucosa covering implants and the amount of closure were evaluated macroscopically. Light microscopy, histomorphometry, immunohistochemistry, and transmission electron microscopy were performed to assess soft-tissue growth and differentiation. Statistical analysis was performed by means of the Mann-Whitney test.The mean rate of mucoperichondrial flap recovery of the implant was 66 percent in group 2 and 82 percent in group 3, and was significantly different from that of the control group (p < 10−4). The mean amount of closure was 32 and 64 percent, respectively (p < 10−3). The thickness of the perichondrium was greater than the control on both sides (p < 10−4). Vascularized soft tissues and bone formation invaded pores of implants. No pathologic inflammation was observed in submucosa. Moderately differentiated and well differentiated newly formed epithelium were the most frequent types observed, with good correlation between immunostaining and morphologic features.These data suggest a good biocompatibility of biphasic calcium phosphate and its ability to repair the nasal septum in sheep.