Electrospinning and electrospraying process provides a versatile approach for the fabrication of biocomposite nanofibrous scaffolds (NFS) with structural, mechanical, and biological properties is to mimick the native extracellular matrix. The present study was aimed to fabricate NFS of poly(l-lactic acid)-co-poly(3-caprolactone) (PLACL), silk fibroin (SF) and hydroxyapatite (HA) by blending (b) and spraying (s) methods. The biocomposite NFS were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy, water contact angle, tensile strength, fourier transform infrared spectroscopy (FTIR) analysis. The fabricated biocomposite NFS showed pore size around 1.5-7.8 m and porosity of 68-93% with fiber diameter ranging from 213 +/- 78 to 340 +/- 52nm. Furthermore, the mesenchymal stem cells (MSCs) were cultured on the biocomposite NFS and the cell interaction, proliferation, mineralization, and osteocalcin expression were analyzed by FESEM, MTS assay, alizarin Red S staining, and immunofluorescence analysis, respectively. The presence of bioactive SF/HA molecules supported biological functions namely cell attachment, proliferation, and differentiation of MSCs into osteoblasts. The observed results suggested that the biocomposite PLACL/SF/HA(s) NFS stimulated osteogenic differentiation of MSCs as evident from alkaline phosphatase activity, mineralization, and expression of osteocalcin for bone tissue engineering. (c) 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46756.