Nanoscale organized organic-inorganic nanocomposite systems have great potential in the development of biomaterials with advanced properties. Herein, we developed a novel nanocomposite biomaterial consisting of bioactive glass nanofiber (BGNF) and collagen reconstituted fibrous matrix for bone regenerative medicine. A sol-gel derived glass with a bioactive composition (58SiO(2). 38CaO.4P(2)O(5)) was electrospun to a nanoscale fiber with an average diameter of approximately 320 nm. The BGNF was subsequently hybridized with type I collagen, which is the main organic constituent of bone matrix. The BGNF and self-assembled collagen sol were combined in aqueous solution, and then crosslinked to produce a BGNF-collagen nanocomposite, in the form of either a thin membrane or a macroporous scaffold, by adopting appropriate processing conditions. The BGNF was observed to be distributed uniformly within the collagen reconstituted nanofibrous matrix. The nanocomposite matrices induced rapid formation of bone-like apatite minerals on their surfaces when incubated in a simulated body fluid, exhibiting excellent bioactivity in vitro. Osteoblastic cells showed favorable growth on the BGNF-collagen nanocomposite. In particular, the alkaline phosphatase activity of the cells on the nanocomposite was significantly higher than that on the collagen. This novel BGNF-collagen nanocomposite is believed to have significant potential in bone regeneration and tissue engineering applications.