Oyster Shell Powder/PCL Composite Scaffolds Loaded with Psoralen Nanospheres Promote Large Bone Defect Repair

Research on bone substitutes for repairing bone defects has drawn increasing attention, and the efficacy of three-dimensional (3D) printed bioactive porous scaffolds for bone defect repair has been well documented. Our previous studies have shown that psoralen can promote osteogenesis by activating the Wnt/β-catenin and BMP/Smad signaling pathways and their crosstalk effects, and psoralen nanospheres have a good osteogenesis-promoting effect <i>in vitro</i> with low cytotoxicity. The Chinese medicine oyster shell powder, characterized by its porous structure, strong adsorption, and unique bioactivity, has potential in fracture-promoting repair materials. However, the effect of loading psoralen nanospheres onto oyster shell powder/polycaprolactone (OSP/PCL) scaffolds to repair bone defects is unclear. In this study, composite scaffolds consisting of OSP PCL were prepared by 3D printing, and psoralen nanospheres were adhered to the scaffolds. The characterization features of the composite scaffold system were investigated <i>in vitro</i> concerning the biocompatibility of bone mesenchymal stem cells (BMSCs). The efficacy of the composite scaffolds for repairing bone defects was explored <i>in vivo</i> through a rat cranial bone defect model. The results showed that the composite scaffolds were homogeneous porous structures with high mechanical strength and could be adhered well by the psoralen-loaded nanospheres. <i>In vitro</i> studies showed that the scaffolds had good biocompatibility with BMSCs and positively affected the expression of osteogenic differentiation-related proteins. <i>In vivo</i> studies showed that the composite scaffolds could more effectively promote the formation of new bone in the defect area (Φ5 mm) compared to the pure PCL scaffolds. At the same time, the composite scaffolds containing psoralen had a more significant stimulating effect on the healing of the cranial defects compared with the OSP/PCL scaffolds without psoralen.