The aim of the present study was to evaluate the biocompatibility and bone mineralization potential of 45S5 Bioglass-derived glass-ceramic scaffolds using a chick embryo shell-less (ex ovo) culture system. Chick embryos were divided into two groups: control (C) and experimental (E). Scaffolds were placed on the chorioallantoic membrane (CAM) in embryos of group E at 10 days of total incubation. The 45S5 Bioglass-derived glass-ceramic scaffolds proved to be biocompatible in terms of the absence of inflammatory response at the implant site (CAM). Moreover, no alterations in the other end-points assessed, i.e. survival, stage of embryonic development and body weight, were detected. However, body length was greater in group E embryos than in group C embryos (p0.05). A marked reduction (93%) in Ca content in the scaffolds was evidenced by energy-dispersive X-ray analysis at 5 days post-implantation. Calcium release from the scaffold implanted on the CAM might have been responsible for the restoration of the bone-like phenotype in chick embryonic skeleton of group E as detected by Alcian blue-Alizarin red double staining, as well as by histological and microchemical analyses. Conversely, the control embryos exhibited a chondrogenic phenotype.