Components of gelatin/polycaprolactone (PCL) electrospun scaffolds are released to surrounding media and cause osmotic changes that adversely affect cell viability and proliferation. In this study, the physiological properties of gelatin/PCL scaffolds were investigated by qRT-PCR and by performing cellular studies on HEK 293 cells. Components released from gelatin/PCL scaffolds were found to induce osmotic stress response in these cells. However, osmotic stress was inhibited by adding fetal bovine serum (FBS) to scaffolds. In addition, focal adhesion related genes were found to be up-regulated in HEK 293 cells on gelatin/PCL/20% FBS scaffolds, and this induced the down-regulations of cell-death related genes. Furthermore, the inclusion of 20% FBS improved the viabilities of HEK 293 cells on gelatin/PCL scaffolds. This study indicates that adding FBS to gelatin/PCL scaffolds improves scaffold bio-affinity. (c) 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013