3D-printable chitosan/silk fibroin/cellulose nanoparticle scaffolds for bone regeneration via M2 macrophage polarization.

Biopolymers-induced immune microenvironment exhibited prominent effects on bone regeneration. Osteo-immunomodulatory responses of cellulose nanoparticles incorporated chitosan hydrogel scaffolds have not yet been reported. The objective of this study was to monitor the synergistic effects of silk fibroin and cellulose nanoparticles on the immune-modulatory behavior of chitosan biopolymer scaffolds. 3D-printed biodegradable cellulose nanoparticles-reinforced chitosan/silk fibroin (CS/SF/CNPs) scaffolds were fabricated and characterized by different spectroscopic techniques. The improved rheological and recovery strength was observed in CS/SF/CNPs hydrogels than pure polymer hydrogels. A significant shift from M1 → M2 macrophages polarization occurred in the CS/SF/CNPs scaffolds treated groups than the control after 3 days of incubation, showing its immune-modulatory potential. Osteo-immunomodulatory effects of the fabricated scaffolds were analyzed on human bone marrow-derived mesenchymal stem cells (hBMSCs), with macrophages-derived conditioned media (M-CM). Enhanced bone regeneration was observed in the calvaria defect rat model, indicating that the fabricated scaffolds are promising materials for bone-healing applications.