High-performance biomaterials were aimed to be prepared for bone regeneration by hybridizing borosilicate with poly(vinyl alcohol)s (PVAs), incorporating Ca(II) sources, and formulating the resulting composites into mesoporous aerogels. The hybridization of borosilicate with different molecular weight PVAs was realized in a sol−gel procedure, yielding homogeneous hydrogels. These gels were functionalized in the sol−gel process by microcrystalline Ca(II) sources [CaCl 2 , β-Ca 3 (PO 4 ) 2 , hydroxyapatite/Ca 10 (PO 4 ) 6 (OH) 2 ], and finally converted to nanostructured monolithic aerogels by solvent exchange and drying in supercritical CO 2 . The chemical structures of the solid backbones were elucidated by infrared spectroscopy and solid-state NMR. Energy-dispersive X-ray spectroscopy, elemental analysis, and X-ray diffraction were used to characterize the incorporated Ca(II) sources. The nanoscale morphological features of the functionalized hybrid aerogels were characterized using scanning and transmission electron microscopy, N 2 porosimetry, and small-angle neutron scattering (SANS). Contrast variation SANS measurements confirmed the formation of a homogeneous yet nanostructured hybrid from borosilicate and PVA in all cases. In vitro tests were performed in the presence of suspended aerogel microparticles using the MG-63 osteosarcoma cell line and dental pulp stem cells. Quantitative time-lapse video microscopy measurements demonstrated the biocompatibility and biostimulating effect of the hybrid aerogel particles. These beneficial properties are attributed to the carefully designed chemical composition, porosity, and negative ζ-potential of the aerogel particles.