A 3D Printed Bone Tissue Engineering Scaffold Composed of Alginate Dialdehyde‐Gelatine Reinforced by Lysozyme Loaded Cerium Doped Mesoporous Silica‐Calcia Nanoparticles

AbstractA novel biomaterial comprising alginate dialdehyde‐gelatine (ADA‐GEL) hydrogel augmented by lysozyme loaded mesoporous cerium doped silica‐calcia nanoparticles (Lys‐Ce‐MSNs) is 3D printed to create bioactive scaffolds. Lys‐Ce‐MSNs raise the mechanical stiffness of the hydrogel composite scaffold and induce surface apatite mineralization, when the scaffold is immersed in simulated body fluid (SBF). Moreover, the scaffolds can co‐deliver bone healing (Ca and Si) and antioxidant ions (Ce), and Lys to achieve antibacterial (and potentially anticancer) properties. The nanocomposite hydrogel scaffolds can hold and deliver Lys steadily. Based on the in vitro results, the hydrogel nanocomposite containing Lys assured improved pre‐osteoblast cell (MC3T3‐E1) proliferation, adhesion, and differentiation, thanks to the biocompatibility of ADA‐GEL, bioactivity of Ce‐MSNs, and the stabilizing effect of Lys on the scaffold structure. On the other hand, the proliferation level of MG63 osteosarcoma cells decreased, likely due to the effect of Lys. Last but not least, cooperatively, alongside gentamicin (GEN), Lys brought about a proper antibacterial efficiency to the hydrogel nanocomposite scaffold against gram‐positive and gram‐negative bacteria. Taken together, ADA‐GEL/Lys‐Ce‐MSN nanocomposite holds great promise for 3D printing of multifunctional hydrogel bone tissue engineering (BTE) scaffolds, able to induce bone regeneration, address infection, and potentially inhibit tumor formation and growth.