Bionic Mineralized 3D-Printed Scaffolds with Enhanced In Situ Mineralization for Cranial Bone Regeneration

In situ mineralization is a promising strategy to mimic the physicochemical properties of biominerals and is widely applied in the field of bone repair. Given the high requirement for substance exchange in cranial bone regeneration, in situ mineralized organic-inorganic hybrid materials exhibit advantages. However, the integration of remarkable mineral content, mechanical properties, and osteogenic properties also remains a major challenge. Herein, enhanced in situ mineralization through combining the enzymatic and anion-boosted mineralization is applied to promote the mineralization efficiency, mineral content, and mechanical properties. Based on the results of computational calculations and in vitro mineralization experiments, the mechanism of mineralization enhancement is investigated from the perspectives of nucleation sites and the saturation of in situ mineralization. Anionic polyaspartic acid (pAsp) can increase the saturation of in situ mineralization; enzymatic mineralization shows high efficiency, with minerals of low crystallinity. The changes in the properties of the minerals effectively enhance the biological properties of 3D-printed scaffolds, as confirmed by cell proliferation/differentiation experiments in vitro and in cranial bone regeneration in vivo. This strategy provides a new thinking for the preparation of bionic mineralized scaffolds for cranial bone repair, and can greatly promote the efficiency of bone regeneration. The anion (pAsp)-boosted mineralization and enzyme-induced mineralization are integrated to increase the efficiency and the saturation of in situ mineralization. The combination of DFT calculation, in vitro mineralization experiments, and 3D printing helps the construction of enhanced-mineralized porous scaffolds, which promotes the osteogenic differentiation of bone marrow mesenchymal stem cells and accelerates the reconstruction of cranial defects.image