Controlling inflammation meanwhile facilitating tissue regeneration has been considered as a promis-ing strategy to treat inflammatory bone defect.Herein,we describe the synthesis of a bio-sensitive poly(lactic-co-glycolic acid)/mesoporous silica nanocarriers core-shell porous microsphere(PLGA/MSNs-PMS)encapsulated poly(L-lactic acid)(PLLA)spongy nanofibrous micro-scaffold as a new generation of therapeutic platform for effective reconstruction of bone defects caused by periodontal diseases.The PLGA/MSNs-PMS were designed as stimuli-responsive carriers for on-demand co-delivery of mul-tiple biomolecules to provide proper physiological environment,while the multi-level(from macro-,micro-to nanometers)nanofibrous and porous structures in PLLA micro-scaffold were in charge of the reconstruction of ECM,which synergistically contribute to the enhancement of new tissue formation under inflammatory condition.After local injection into periodontal tissue,this construct could sequen-tially release bone growth factor(BMP-2)as well as anti-inflammatory drug(celecoxib)loaded MSNs in response to the over-expressed matrix metalloproteinases(MMP)in periodontal region.During alveolar bone regeneration induced by BMP-2 and ECM like structure,the MSNs would further deliver celecoxib in target cells to achieve inflammation inhibition,resulting in effective treatment of periodontal disease.