One of the major problems associated with the electrospun scaffolds is their small pore size, which limits the cellular infiltration for bone tissue engineering. In this study, the effect of increasing the pore size on cellular infiltration was studied in poly/nanohydroxyapatite electrospun scaffolds, which were modified using ultrasonication, co-electrospinning with poly (ethylene oxide), and a combination of both. Ultrasonic process was optimized by central composite design. The ultrasonic output power and time of the process were considered as the effective parameters. The pore size of the scaffolds was evaluated by scanning electron microscope. The optimum conditions, according to the pore area and mechanical properties of the scaffolds were selected, and finally the groups that had the highest pore size and mechanical strength were selected for the combined method. Increasing the pore size enhanced the cellular proliferation, extension and infiltration, as well as the osteodifferentiation of stem cells. At the optimum condition, the average cellular infiltration was 36.51 mu m compared to the control group with no cellular infiltration. In addition, alkaline phosphatase activity and the expression of osteocalcin and collagen I (COL I) were, respectively, 1.86, 2.54, and 2.16 fold compared to the control group on day 14. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1887-1899, 2017.