Tissue engineering and regenerative medicine have evolved into a different concept, the so-called clinical tissue engineering. Within this context, the synthesis of next-generation inorganic-organic hybrid constructs without the use of chemical crosslinkers emerges with a great potential for treating bone defects. Here, we propose a sophisticated approach for synthesizing cost-effective boron (B)- and silicon (Si)-incorporated collagen/hair keratin (B-Si-Col-HK) cryogels with the help of sol-gel reactions. In this approach, collagen and hair keratin were engaged with a B-Si network using tetraethyl orthosilicate as a silica precursor, and the obtained cryogels were characterized in depth with attenuated total reflectance-Fourier transform infrared spectroscopy, solid-state NMR, X-ray diffraction, thermogravimetric analysis, porosity and swelling tests, Brunauer-Emmett-Teller and Barrett-Joyner-Halenda analyses, frequency sweep and temperature-dependent rheology, contact angle analysis, micromechanical tests, and scanning electron microscopy with energy dispersive X-ray analysis. In addition, the cell survival and osteogenic features of the cryogels were evaluated by the MTS test, live/dead assay, immuno/histochemistry, and quantitative real-time polymerase chain reaction analyses. We conclude that the B-Si-networked Col-HK cryogels having good mechanical durability and osteoinductive features would have the potential bone formation capability.