A potential bone substitute and drug carrier system is prepared to be used in treatment of serious bone infections like osteomyelitis. Vancomycin (VAN), as an antibiotic was loaded into ZIF8 nanocrystals for a pH responsive controlled release (ZIF8/VAN). Chitosan scaffolds loaded with ZIF8/VAN were prepared by wet-spinning to obtain 3D biocompatible scaffolds. Characterization of scaffolds were performed to determine the morphology, swelling behavior and pH controlled VAN release. Antibacterial activity studies were done to investigate the effectiveness of the carrier system against Staphylococcus aureus. VAN molecule encapsulation efficiency for nanosized ZIF8 crystals was calculated as 99.3%. The results showed that the VAN loaded to ZIF8 nanocrystals was released in a pH controlled manner from the chitosan scaffolds. About 70% of the VAN was released during 8 h at pH 5.4, while this value was 55% at pH 7.4. VAN release was increased with higher dissolution of ZIF8 in acidic conditions and reached a plateau value of ~77% at the end of 48 h at pH 5.4 conditions. ZIF8 and ZIF8/VAN chitosan scaffolds showed a strong effect in the reduction of S. aureus activity in comparison to chitosan scaffolds alone. This effect was best pronounced under pH 5.4 conditions which can mimic the environment of an inflamed tissue. MC3T3-E1 preosteoblasts showed high proliferation and osteogenic activities on ZIF8 loaded chitosan scaffolds.