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BACKGROUND: Psoralen is a plant estrogen, and a large number of studies have confirmed its role in promoting cell proliferation and differentiation. OBJECTIVE: To construct a cell-scaffold composite bone using psoralen, rabbit endosteal mesenchymal stem cells and polycaprolactone and to explore its effect on the treatment of rabbit nonunion. METHODS: (1) Rabbit endosteal mesenchymal stem cells were cultured and cultured until the third generation for each experiment. Passage 3 cells were seeded onto culture plates containing 50 mg/L bone morphogenetic protein 2 (positive control), 10-8, 10-7 and 10-6 mol/L psoralen (low-, middle-, and high-concentration psoralen groups) or the same volume of purified water (control group). The cell proliferation of each group was detected on the 3rd, 5th and 7th days after intervention using MTT method. (2) The three-dimensional polycaprolactone scaffold was added to the bottom of the cell culture plate, and rabbit endosteal mesenchymal stem cells were seeded into the scaffold at a density of 1×10³ per well. Then, 10-6 mol/L of psoralen was added. Cell-scaffold composite bone was taken after 21 days of culture. (3) Animal models of radial nonunion were established in 27 New Zealand white rabbits, and were then randomized into experimental, scaffold and control groups followed by implantation of cell-scaffold composite bone, simple scaffold, and nothing, respectively. Pathological hematoxylin-eosin staining for observation of bone healing was performed at the 2nd, 4th, and 8th weeks after surgery. Healing of nonunion was observed on the X-ray films that were taken at the 4th week after surgery. RESULTS AND CONCLUSION: (1) Three concentrations of psoralen could induce the proliferation of rabbit endosteal mesenchymal stem cells. Compared with the control group, 10-6 mol/L psoralen exerted the strongest stimulation effect on rabbit endosteal mesenchymal stem cells (P < 0.05), whereas there was no significant difference between high-concentration psoralen group positive control group (P > 0.05). (2) Pathological hematoxylin-eosin staining of radial nonunion showed that the number of osteoblasts in the experimental group was higher than that in the scaffold and control groups (P < 0.05). (3) The X-ray films revealed bone healing in the experimental group, partial healing in the scaffold group and non-healing in the control group. Overall findings indicate that psoralen can promote the proliferation of rabbit endostealmesenchymal stem cells, and the effect is certainly related to the concentration of psoralen. Psoralen can be combined with rabbit endosteal mesenchymal stem cells and polycaprolactone scaffold to form composite bone, achieving good outcomes in the treatment of nonunion in animals. [ABSTRACT FROM AUTHOR]