Summary form only given. Physical and chemical cues introduced on the microenvironment of cell may alter and regulate the cellular activity. Up to now, the positive effect of plasma modification and protein coating of biopolymer on cell attachment and proliferation has been studied excessively on planar surfaces1. However, based on our knowledge, the synergetic effect of plasma modification and protein coating on 3D scaffolds for long term cellular response including differentiation has not been studied. In this study, we investigated the combinatorial effect of adhesive protein coating and plasma modification on polycaprolactane (PCL) scaffolds for osteoblast differentiation compared to adhesive protein coating and plasma modification alone. We worked on four different groups of scaffolds; unmodified PCL (UP), plasma modified PCL (PP), fibronectin coated PCL (FNP) and plasma modified-fibronectin coated PCL (P-FNP). The surface characterization was done by contact angle measurement, surface energy calculation, surface roughness via atomic force microscopy, surface chemistry via X-ray photoelectron spectroscopy. The biological characterization was done through measuring strength of cellular adhesion, measuring rate of metabolic activity over time, observing early and later stage differentiation rate via alkaline phosphatase activity and osteocalcin secretion. Based on results, we found that rate of cellular differentiation strongly depends on the combination of physical, chemical and biological modification of PCL surfaces. More specifically, the early and later differentiation markers, the alkaline phosphatase activity and osteocalcin expression, increased more rapidly on plasma modified-fibronectin coated (P-FNP) scaffolds compared to UP, FNP, P-FNP.