Bone defects have attracted increasing attention in clinical settings. To date, there have been no effective methods to repair defective bones. Balsa wood aerogels are considered as an excellent source of chemicals for chemical modification to facilitate the in situ immobilization of zeolitic imidazolate framework-8. Furthermore, dexamethasone has received considerable attention for bone tissue engineering. In this study, for the first time, a simple but effective one-pot method for developing a novel zeolitic imidazolate framework-8 with different concentrations of dexamethasone was developed. These findings illustrate that the novel scaffold has a significant positive impact on osteogenic differentiation in vitro and repairs defects in vivo, suggesting that it can be used in bone tissue engineering.