Hypothesis: This study aims at developing biodegradable, mineralized, nanofibrous scaffolds for use in bone regeneration. Scaffolds are loaded with combinations of bone morphogenic protein-2 (rhBMP-2) and transforming growth factor beta (TGF-beta) and evaluated in vitro for enhancement in osteoinductivity. Experiments: Poly(epsilon-caprolactone) (PCL) doped with different portions of nano-hydroxyapatite is electrospun into nanofibrous scaffolds. Non-mulberry silk fibroin (NSF) obtained from Antheraea mylitta is grafted by aminolysis onto them. Scaffolds prepared have three concentrations of nano-hydroxyapatite: 0% (NSF-PCL), 25% (NSF-PCL/n25), and 50% (NSF-PCL/n50). Growth factor loading is carried out in three different combinations, solely rhBMP-2 (BN25), solely TGF-beta (TN25) and rhBMP-2 + TGF-beta (T/B N25) via carbodiimide coupling. Findings: NSF-PCL/n25 showed the best results in examination of mechanical properties, bioactivity, and cell viability. Hence only NSF-PCL/n25 is selected for loading growth factors and subsequent detailed in vitro experiments using MG-63 cell-line. Both growth factors show sustain release kinetics from the matrix. The T/B N25 scaffolds support cellular activity, proliferation, and triggering of bone-associated genes' expression better and promote earlier cell differentiation. Dual growth factor loaded NSF grafted electrospun PCL/nHAp scaffolds show promise for further development into a suitable scaffold for bone tissue engineering. (C) 2016 Elsevier Inc. All rights reserved.