ABSTRACT Bone lesions that cannot regenerate spontaneously remain a significant clinical challenge, hindering effective management and functional recovery. Bone tissue engineering offers a promising approach to improve regeneration. This study aimed to develop a bioactive cement as an in situ hardening scaffold composed of chitosan, nano‐hydroxyapatite (n‐HA), and other components, incorporating varying concentrations of lithium to enhance the osteogenic differentiation of human dental pulp stem cells (hDPSCs). The physicochemical and biological properties of the scaffolds were evaluated by measuring setting time, bioactivity, lithium release profile, and cellular responses using Scanning Electron Microscopy (SEM), X‐ray diffraction (XRD), MTT assay, and Alkaline Phosphatase (ALP) activity. The results showed that lithium incorporation did not significantly affect the setting time. SEM and XRD analyses confirmed the formation of a bone‐like apatite layer on scaffold surfaces after immersion in Simulated Body Fluid (SBF). Lithium release profiling revealed dose‐dependent kinetics: while all groups showed an initial release, the Li/n‐HA/Ch‐200 group exhibited a distinctive delayed peak of 3.96 mg/L on Day 3, followed by a decline to non‐toxic levels. Biological assays demonstrated that the scaffolds supported hDPSCs attachment, with the Li/n‐HA/Ch‐100 group maintaining significantly higher cell proliferation at Day 14 ( p < 0.01). Notably, lithium‐loaded scaffolds strongly enhanced osteogenic differentiation; specifically, the Li/n‐HA/Ch‐200 group showed superior ALP activity compared to controls, achieving high statistical significance ( p < 0.0001). These findings suggest that Li/n‐HA/Ch scaffolds provide a potent short‐term therapeutic release of lithium to stimulate osteogenesis, positioning them as promising candidates for bone tissue engineering applications.
eydi et al. (Sun,) studied this question.