For hybrid materials, molecular interactions between inorganic and organic phases which are dependent upon the solvent and the procedure through which a hybrid is synthesized, directly affect the macroscopic properties. We report herein the effect of solvent (dimethylformamide (DMF) and dimethyl sulfoxide (DMSO)) and synthesis route (freeze drying or heat treatment) on structural and microstructural properties, thermal stability and the apatite forming ability of silica/poly (amido amine) generation 5 (PAMAM G5) class II hybrids. Thorough investigations of the hybrids allowed us to prove the covalent coupling between inorganic and organic chains and inorganic condensation, as well as the nanoscale interactions and co-network of inorganic and organic phases. Furthermore, thermal stability and silica network dissolution were studied and a clear conclusion was drawn as to improved thermal stability and a steady degradation is achieved by incorporation of silica phase and a coupling agent. The biomineralization capability of hybrids was evaluated by immersing in simulated body fluid (SBF) for 1 week. SEM, ICP-OES, FTIR and XRD showed that hybrids synthesized by both DMF and DMSO could form, although with different morphologies, an apatite layer on their surface and therefore are highly bioactive. Our results suggest that silica/PAMAM G5 hybrids could further have promising applications in bone tissue engineering. (C) 2017 Elsevier B.V. All rights reserved.