To develop a hybrid scaffold that enhances bone regeneration and preventing infections by integrating polycaprolactone (PCL) scaffolds for mechanical support with bacterial cellulose (BC) membranes for psoralen (Pso) delivery,aiming to improve open bone defect treatment. PCL scaffolds were fabricated via 3D printing, and BC was extracted from fungi to prepare three types of scaffolds: PCL, BC-PCL, and BC-Pso-PCL. The scaffolds were characterized through scanning electron microscopy (SEM), contact angle measurement, and infrared spectroscopy. Biocompatibility was assessed by cytotoxicity (CCK-8) assay, cell migration assay, live/dead cell staining, and cell proliferation experiments. Antibacterial effects were tested under a simulated bacterial environment. Osteogenic performance was evaluated by alkaline phosphatase (ALP) activity, Alizarin red staining(ARS), and immunofluorescence after osteogenic induction. Quantitative PCR (qPCR) and Western blotting (WB) were performed to analyze bone regeneration and angiogenesis markers. Bone regeneration efficacy was assessed in vivo using a 5 mm critical-sized cranial bone defect model in rats(Figure 1A-C). Biocompatibility studies demonstrated that all three scaffolds showed good biocompatibility. Under Staphylococcus aureus exposure, BC-Pso-PCL effectively inhibited bacterial growth. The ALP and ARS results following osteogenic induction indicated that the BC-Pso-PCL group exhibited superior ALP activity and mineralized nodule formation compared to other groups. Subsequent immunofluorescence, qPCR and Western blot further confirmed the outstanding osteogenic performance of BC-Pso-PCL. In vivo experiments demonstrated that the BC-Pso-PCL scaffold achieved the highest level of new bone formation in rat cranial defects. The BC-Pso-PCL scaffold not only demonstrated superior biocompatibility in cytotoxicity, cell migration, live/dead staining, and proliferation assays, but also promoted bone regeneration and angiogenesis. The in vivo study further confirmed the superior bone formation achieved by BC-Pso-PCL. These findings highlight the potential of BC-Pso-PCL as an implantable scaffold for the treatment of open bone defects, providing a promising solution for future clinical applications.