3-D printing of chitosan-MSN@dexamethasone scaffold with enhanced properties for bone tissue engineering

Bone tissue engineering (BTE) is an attempt to overcome the limitations of conventional grafting through the combination of bioactive scaffolds and regenerative signals. In this study, we prepared an extrusion-based 3D-printed composite scaffold composed of chitosan (CH) combined with dexamethasone (DEX)-loaded mesoporous silica nanoparticle (MSN), (MSN@DEX) in order to compensate for both mechanical insufficiency and temporary osteoinductive signal. MSNs were synthesized by a templated sol-gel method with high drug loading efficiency and biphasic release behavior. Inclusion of MSN@DEX in chitosan resulted in scaffolds with homogeneous and interconnected porosity (310-420 μm), high compressive strength, good swelling profile, and a degradation profile consistent with the time course of bone healing. In vitro experiments with mesenchymal stem cells (MSCs) resulted in a high hemocompatibility, a sustained cell proliferation and a significantly enhanced osteogenic differentiation given by alkaline phosphatase (ALP) activity, calcium deposits and stage-dependent upregulation of RUNX2, ALP, COL1A1 and OCN genes and protein. Together, the hierarchical scaffold architecture, nanostructured reinforcement, and local sustained DEX release provide a cost-effective, stable and clinically adaptable platform for robust osteogenesis with the possibility of enhanced osteogenic induction even with lower dexamethasone release. These findings underscore the potential of CH‑MSN@DEX scaffolds for bone regeneration applications. By combining structural reinforcement with sustained osteoinductive signaling within a single printable construct, this approach represents a clear advancement over previously reported chitosan‑based or DEX‑releasing scaffold systems.