Bead-on-string nanofibers, with appropriate control of the beads diameter, are potential fibrous structures for efficient encapsulation of particle drugs in micron scales and could achieve controlled drug release for tissue engineering applications. In this study, the beads diameter of electrospun bead-on-string nanofibers Was controlled by adjusting the concentration of spinning polymer, poly (lactic-co-glycolic acid) (PLGA), and the solvent ratio of chloroform to acetone. The images of the scanning electron microscopy (SEM) suggested that bead-on-string nanofibers could be successfully obtained only with a certain range of PLGA solution concentration. Moreover, with the decrease in the solvent ratio of chloroform to acetone, the range was left-shifted towards a smaller concentration. In addition, increase in the PLGA solution concentration within the range the beads diameter became greater and the shape of the beads changed from oval to slender when increasing the PLGA concentration within the range. The bead-on-string nanofibers with different beads diameter were further used to load micro-particle drugs of tetracycline hydrochloride, as a model drug, to examine the release behavior of nanofibers scaffold. The release profiles of drug loaded bead-on-string nanofibers demonstrated the possibility to alleviate the burst drug release by means of beads diameter control. (C) 2016 Elsevier B.V. All rights reserved.