Platelet-rich plasma (PRP) is used in therapy for bone tissue repair because an abundance of osteogenesis-related growth factors can be released from the concentrated platelets. However, its clinical use is limited because growth factors, temporally released from PRP, are degraded rapidly. This study aimed to incorporate PRP-derived growth factors into SF/PCL/PVA nanofibers by coaxial electrospinning to determine the release profiles of growth factors and how the presence of these growth factors enhances the osteogenic abilities of the nanofibers. Scaffolds containing different ratios of PRP and PVA were prepared and characterized. We then quantified the release of growth factors from the nanofibers over time, and evaluated the proliferation, migration and osteogenic differentiation of MSCs. The in vivo osteogenic capacity of the PRP-containing core-shell NFS was also evaluated by transplanting the PRP/MSCs/CS/β-TCP compounds into the skin on the back of nude mice and by treating cranial defects of C57BL/6 mice. The results of such treatments were analyzed by immunofluorescent staining, μ computed tomography (μCT), and histological observation. The results show that coaxial nanofibers with a PRP-5% PVA solution ratio of 7:1 contained a relatively high amount of PRP and exhibited a more uniform distribution of fiber diameters. The bioactivity of the scaffolds was enhanced due to the increased proliferation and migration of bone marrow mesenchymal stem cells (BMSCs). When the cells were inoculated and cultured on the PRP-loaded nanofibrous mats, the expression of collagen type II also increased. Furthermore, new bone formation was also promoted by PRP-NFS after 8 weeks of implantation. In conclusion, this study shows that the incorporation of PRP had positive effects on the bioactivity and osteogenic ability of coaxial nanofibrous mats. Such nanofibrous mats may prove beneficial in various applications of bone tissue engineering.