A 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.

In this study, a wound dressing composed of an alginate dialdehyde−gelatin (ADA-GEL) hydrogel incorporated by astaxanthin (ASX) and 70B (70:30 B 2 O 3 /CaO in mol %) borate bioactive glass (BBG) microparticles was developed through 3D printing. ASX and BBG particles stiffened the composite hydrogel construct and delayed its in vitro degradation compared to the pristine hydrogel construct, mainly due to their cross-linking role, likely arising from hydrogen bonding between the ASX/BBG particles and ADA-GEL chains. Additionally, the composite hydrogel construct could hold and deliver ASX steadily. The composite hydrogel constructs codelivered biologically active ions (Ca and B) and ASX, which should lead to a faster, more effective wound-healing process. As shown through in vitro tests, the ASXcontaining composite hydrogel promoted fibroblast (NIH 3T3) cell adhesion, proliferation, and vascular endothelial growth factor expression, as well as keratinocyte (HaCaT) migration, thanks to the antioxidant activity of ASX, the release of cell-supportive Ca 2+ and B 3+ ions, and the biocompatibility of ADA-GEL. Taken together, the results show that the ADA-GEL/BBG/ASX composite is an attractive biomaterial to develop multipurposed wound-healing constructs through 3D printing.