PurposeIn this study, we aimed to develop a unique N-acetyl cysteine (NAC)-loaded polylactic-co-glycolic acid (PLGA) electrospun system with separate compartments for the promotion of osteogenesis.Materials and methodsWe first prepared solutions of NAC-loaded mesoporous silica nanoparticles (MSNs), PLGA, and NAC in N, N-dimethylformamide and tetrahydrofuran for the construction of the electrospun system. We then fed solutions to a specific injector for electrospinning. The physical and chemical properties of the scaffold were characterized through scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. The release of NAC and Si from different PLGA scaffolds was estimated. The cell viability, cell growth, and osteogenic potential of rat bone marrow-derived stroma cell (rBMSCs) on different PLGA scaffolds were evaluated through MTT assay, live/dead staining, phalloidin staining, and Alizarin red staining. The expression levels of osteogenic-related markers were analyzed through real-time PCR (qRT-PCR).ResultsNAC was successfully loaded into MSNs. The addition of MSNs and NAC decreased the diameters of the electrospun fibers, increased the hydrophilicity and mechanical property of the PLGA scaffold. The release kinetic curve indicated that NAC was released from (PLGA + NAC)/(NAC@MSN) in a biphasic pattern, that featured an initial burst release stage and a later sustained release stage. This release pattern of NAC encapsulated on the (PLGA + NAC)/(NAC@MSN) scaffolds enabled to prolong the high concentrations of release of NAC, thus drastically affecting the osteogenic differentiation of rBMSCs.ConclusionA PLGA electrospun scaffold was developed, and MSNs were used as separate nanocarriers for recharging NAC concentration, demonstrating the promising use of (PLGA + NAC)/(NAC@MSN) for bone tissue engineering.