© 2020 The Society for Biotechnology, JapanDesign and fabrication of biologically active cryogels using novel biopolymer(s) are still of great importance at regenerating bone defects such as traumatic bone injuries, maxillofacial surgery, osteomyelitis, and osteoporosis. Nowadays, plant mucilage, an herbal biomaterial, has been drawn attention by scientists due to their marvelous potential to fabricate 3-dimensional (3D) physical constructs for the field of regenerative medicine. Herein, a 3D cryogel from silicon-integrated quince seed mucilage (QSM) is constructed using microwave-assisted sol–gel reaction, characterized in-depth by attenuated total reflectance Fourier transform-infrared spectroscopy (ATR-FTIR), solid-state silicon cross-polarization magic-angle nuclear magnetic resonance (29Si-CP-MAS NMR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimeter (DSC), micro-mechanical testing, porosity, and swelling tests, contact angle measurements, Brunauer-Emmet-Teller and Barret-Joyner-Halenda (BET-BJH) analysis, enzymatic biodegradation test, and field emission-scanning electron microscopy-energy dispersive X-ray spectroscopy (FE-SEM-EDX) mapping. The osteobiologic capacity of the cryogels is determined using human adipose-derived mesenchymal stem cells (hAMSCs) under in vitro conditions. Osteogenic differentiation of hAMSCs on both QSM and silica-modified QSM (Si-QSM) cryogels is analyzed by histochemistry, immunohistochemistry, and quantitative-real time (q-RT) PCR techniques. The results obtained from in vitro experiments demonstrate that the upregulation of osteogenesis-related genes in Si-QSM cryogels presents a stronger and earlier development over QSM cryogels throughout the culture period, which in turn reveals the great potential of this novel Si-incorporated QSM cryogels for bone tissue engineering applications.