Organic-inorganic hybrid materials, composed of phases that interact on a nanoscale and a microstructure that mimics the extracellular matrix, can potentially provide attractive scaffolds for bone regeneration. In the present study, hybrid scaffolds of gelatin and bioactive glass (BG) with a fibrous microstructure were prepared by a combined sol-gel and electrospinning technique and evaluated in vitro. Structural and chemical analyses showed that the fibers consisted of gelatin and BG that were covalently linked by 3-glycidoxypropyltrimethoxysilane to form a homogeneous phase. Immersion of the gelatin-BG hybrid scaffolds in a simulated body fluid (SBF) at 37 degrees C resulted in the formation of a hydroxyapatite (HA)-like material on the surface of the fibers within 12 h, showing the bioactivity of the scaffolds. After 5 days in SBF, the surface of the hybrid scaffolds was completely covered with an HA-like layer. The gelatin-BG hybrid scaffolds had a tensile strength of 4.3 +/- 1.2 MPa and an elongation to failure of 168 +/- 14%, compared to values of 0.5 +/- 0.2 MPa and 63 +/- 2% for gelatin scaffolds with a similar microstructure. The hybrid scaffolds supported the proliferation of osteoblastic MC3T3-E1 cells, alkaline phosphatase activity, and mineralization during in vitro culture, showing their biocompatibility. The results indicate that these gelatin-BG hybrid scaffolds prepared by a combination of sol-gel processing and electrospinning have potential for application in bone regeneration. (C) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 127: 2588-2599, 2013