Timely delivery of bone marrow mesenchymal stem cells based on the inflammatory pattern of bone injury environment to promote the repair of calvarial bone defects in rats: An optimized strategy for bone tissue engineering

Stem cell-based therapy plays a significant role in the repair of bone defects. However, traditional stem cell transplantation strategies in bone tissue engineering are characterized by low survival rates and unstable treatment outcomes. In this study, we propose a timely delivery strategy for inflammatory changes in the setting of bone injury to improve the survival rate of transplanted cells and bone repair. The results of cell tracing in vivo showed that this strategy could effectively improve the survival rate of low-dose exogenous transplanted cells in bone defect areas, and CD31 immunofluorescence and histological sections suggested that this strategy effectively promoted vascularization and new bone formation in the calvarial defect area. Subsequently, we analyzed the mechanism of action of the "Two-step" strategy from the perspective of inflammatory microenvironment regulation, and the results suggested that the first batch transplanted stem cells caused localized and transient increases in tissue apoptosis levels and inflammatory factors, and recruited macrophage chemotaxis, and the second batch of cells may promote pro-inflammatory - anti-inflammatory transformation of the tissue. Finally, mRNA sequencing results suggest that the first batch cells in the "Two-step" strategy are important initiators in bone repair, which not only actively regulate the immune microenvironment at the bone defect, but also guide richer cellular activity and more positive biochemical responses. Therefore, the "Two-step" strategy leads to efficient inflammatory environment regulation and superior bone repair effects, which may provide an alternative option for the treatment of bone defects in the future. Graphical abstract