Decalcified bone scaffold with dynamic matrix stiffness prepared by mineralization improves bone defect repair

Bone formation is a dynamic process, while the stiffness of extracellular matrix increases dynamically during bone maturation. Matrix stiffness can significantly regulate the stem cell differentiation and bone repair. It is particularly important to develop dynamic stiffness scaffolds to simulate dynamic mechanical microenvironment for bone repair. This study proposed a novel method to achieve dynamic improvement of scaffold stiffness by mineralization, which is a natural process of bone matrix dynamic stiffening. The decalcified bone matrix (DBM)/collagen (Col)/silicon-substituted hydroxyapatite (SiHA) scaffold was constructed by coating the Col/SiHA on the surface of DBM. When the scaffolds contacted with body fluid, the stiffness of scaffolds were enhanced by mineralization, increasing from 9.10 ± 4.42 kPa to 19.77 ± 9.66 kPa in the DBM/Col scaffold and from 40.54 ± 6.25 kPa to 69.40 ± 8.76 kPa in the DBM/Col/SiHA scaffold. The experimental results proved that the DBM/Col/SiHA scaffold with dynamic stiffness had good biocompatibility and could promote the osteogenic differentiation of mesenchymal stem cell. The DBM/Col/SiHA scaffold, when implanted in a rat calvarial defect model, further enhanced bone regeneration and integration, as evidenced by a bone mineral density reaching 285.592 ± 19.611 mg HA ccm^-1at 12 weeks. This research may provide new insights into the application of mineralization-dependent stiffening scaffolds in bone tissue engineering.