To develop a biologically mimetic guided tissue regeneration (GTR) membrane with localized sustained drug release function to prevent infection, coaxial electrospinning technique was conducted to fabricate metronidazole (MNA)-loaded poly (epsilon-caprolactone) (PCL)/zein core/shell nanofibers. The nanofibers displayed a uniform bead-free round morphology as observed by scanning electron microscopy (SEM), and a core/shell structure as confirmed by transmission electron microscopy (TEM). X-ray diffraction (XRD) and differential scanning calorimetry (DSC) characterizations demonstrated that the MNA was well dispersed in the nanofibers matrix. Due to the encapsulation of the hydrophobic zein, the MNA was released in a controlled, sustained manner over 4 days, and the released MNA showed high antibacterial activity towards anaerobic bacteria. In addition, the encapsulation of natural zein resulted in enhanced cell adhesion and proliferation, and the loading of MNA did not show any cytotoxicity. Thus, these results demonstrated that the MNA-loaded core/shell nanofibers had the potential to be used as GTR membranes with antibacterial function for extensive biomedical applications. (C) 2016 Elsevier Inc. All rights reserved.