Maxillofacial bone defects remain a complex clinical challenge due to their complex anatomy and limited regenerative capacity. In this study, a bioactive chitosan (CS) scaffold co-incorporated with nicotinamide mononucleotide (NMN) and naringin (Ng) was designed to stimulate osteogenesis and cellular metabolism for enhanced bone regeneration. Fourier-transform infrared analysis verified successful molecular integration of NMN and Ng within the chitosan framework, while scanning electron microscopy showed a uniformly porous surface favorable for stem-cell adhesion. Dental pulp stem cells (DPSCs) cultured on CS/NMN/Ng scaffolds exhibited enhanced cell proliferation, mitochondrial activity, and osteogenic differentiation compared with unmodified chitosan. At the cellular level, calcium deposition was markedly increased; molecular analysis confirmed up-regulated expression of Runx2, alkaline phosphatase (ALP), and type-I collagen. The bone regenerative capacity was further validated in a rat mandibular defect model, where micro-computed tomography and histological staining demonstrated near-complete closure of the defect with increased bone volume fraction and trabecular density after 8 weeks. Overall, the NMN–naringin-functionalized chitosan scaffold provides a metabolically active, osteoinductive microenvironment that promotes bone regeneration, indicating a translational potential for maxillofacial and craniofacial bone tissue engineering applications.
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