Scaffolds that mimic physico-chemical properties of extracellular matrix (ECM) are valuable to stimulate enhanced ce ll-material interactions for tissue engineering applications. Poly (hydroxyl alkanoates) (PHAs) are versatile natural polyesters which are attractive materials for tissue engineering due to their natural origin, good mechanical properties and enhanced biocompatibility. In this study, we compared interactions of Poly (3-hydroxy butyrate) (PHB) scaffolds fabricated by electrospinning and salt-leaching procedures with monkey epithelial kidney cells (Vero) and mouse mesenchymal stem cells (mMSCs). Our results showed, nanofibrous scaffolds can be a better substrate for cell attachment and morphology. As Schwann cells (SCs) physiologically assist in directing the growth of regenerating axons, we also assessed the potential of PHB/Poly (3-hydroxybutyrate- co -3-hydroxyvalerate) (PHBV) nanofibrous scaffolds for nerve regeneration using SCs. Our experiments indicated that the melting temperatures and crystallinity of PHB/PHBV blends decreased as the PHBV weight ratio increased. Digital image processing analysis also proved SCs orientation along the fiber direction of aligned mats. To improve scaffolds biocompatibility, we also functionalized scaffolds with ECM derived peptides to mimic naturally occurring ECM motifs for nerve regeneration. Briefly, proliferation and neural gene expressions of SCs cultured on bio-functionalized scaffolds increased significantly which suggest that these substrates could serve as a potential scaffold for SCs differentiation and axon myelination. Keywords Poly (hydroxyalkanoates), Scaffold, Schwann cells, Nerve tissue engineering