Transplantation of copper-doped calcium polyphosphate scaffolds combined with copper (II) preconditioned bone marrow mesenchymal stem cells for bone defect repair

Calcium polyphosphate is a bioactive ceramic that possesses similar mineral components to bone and possess good physicochemical properties. However, pure calcium polyphosphate scaffold is brittle, and it is insufficient in promoting vascularization and osteoinductivity. This study was conducted to assess whether copper (Cu) incorporated into calcium polyphosphate could improve the scaffolds' inherent shortcomings. In the experiments, Cu-calcium polyphosphate scaffolds' mechanical strength, biocompatibility, and biodegradability were researched primarily. And then, hypoxia-inducible factor 1-alpha expression along with angiogenesis and osteogenesis potential when the scaffolds treated with the bone marrow mesenchymal stem cells (BMMSCs) were analyzed invitro. In invivo studies, the Cu-calcium polyphosphate scaffolds combined with the liquid extract preconditioned BMMSCs were implanted into animal model to repair the bone defects. Meanwhile, we also evaluate the expression of angiogenic and osteogenic factors. For comparison, Cu-calcium polyphosphate, calcium polyphosphate, and blank control groups were designed. According to the results, proper content of Cu incorporated with calcium polyphosphate (0.1% Cu-calcium polyphosphate) did not significantly change the scaffold's degradation velocity, but it obtained higher compress mechanical strength and Cu-doped scaffolds were less brittle. Besides, these scaffolds incorporated with Cu showed better cytocompatibility and cell proliferation activity. Moreover, after Cu was doped, the hypoxia-inducible factor 1-alpha expression was up-regulated with the angiogenic and osteogenic factors levels increased both in invitro and invivo study. The bone defect healing capacity was accessed, using Cu-calcium polyphosphate combined with preconditioned BMMSCs further enhanced new bone formation and improved hypoxia-inducible factor 1-alpha, alkaline phosphatase, osteocalcin, and vascular endothelial growth factor expression. In conclusion, doped Cu into calcium polyphosphate was an alternative strategy for improving calcium polyphosphate's mechanical property and promoting the osteogenesis and angiogenesis potential. Using Cu-calcium polyphosphate scaffolds combined with Cu preconditioned BMMSCs to treat bone defect could enhance bone defect healing.