Temporal-controlled release of bioactive molecules is of key importance in the clinical translation of tissue engineering techniques. We engineered a core-shell nano-system (TD-NS) that sequentially released transforming growth factor-β1 (TGF-β1)， a chemotactic/proliferating growth factor and dexamethasone (Dex)， an osteo/odontogenic agent in a temporal-controlled manner. In stage-1， there was a rapid release of TGF-β1， reaching a concentration of 2ng/mL of TGF-β1 in 7days to 14days， which tapers subsequently. In stage-2， Dex was released linearly from 9days to 28days. The TD-NS group showed a significantly higher (p<0.05) osteo/odontogenic differentiation compared to the control and free TGF-β1 group (Free-TD) that was further corroborated with histochemical examination. The findings from this study highlighted the potential of temporal-controlled delivery of TGF-β1 and Dex from a single nano-carrier to direct spatial and temporal-control for a cell-free tissue engineering strategy in the treatment of apical periodontitis.