Abstract: BACKGROUND: The clinical success of bone grafts depends not only on osteogenesis, but also on angiogenesis, and the ability to inhibit osteoclast-mediated bone resorption. Therefore, it is particularly important to develop bio-scaffold materials with multiple functions. 
OBJECTIVE: To improve various problems of traditional bone repair materials, such as low mechanical strength, poor vascular promoting ability, and insufficient osteoinductive ability through the doping of trace elements. 
METHODS: A series dose of Eu (0%, 1%, 3%, 5% and 7%, molar ratio) was incorporated into calcium polyphosphate scaffolds by high temperature sintering to achieve a multifunctional europium-doped calcium polyphosphate. Infrared spectroscopy, X-ray diffraction analysis, X-ray photoelectron spectroscopy, scanning electron microscopy, mercury intrusion method and compressive strength test were used to characterize its structure, crystal form, element composition, pore size distribution, and mechanical properties. The europium-doped calcium polyphosphate scaffold was co-cultured with mouse embryonic osteoblast precursor cells and human umbilical vein endothelial cells. Biological performance was evaluated through cell proliferation detection, scanning electron microscope, laser scanning confocal microscope, and enzyme-linked immunosorbent assay.  
RESULTS AND CONCLUSION: (1) The doping of Eu3+ did not change the main chain structure and crystal form of calcium polyphosphate, but it could stabilize the pore size distribution within 200-400 μm, which was conducive to bone ingrowth. (2) Compared to pure calcium polyphosphate materials, the crystal grains of europium-doped calcium polyphosphate scaffolds were bonded more closely and ranged well-ordered, which were beneficial to improve mechanical strength of materials. (3) The surface roughness of europium-doped calcium polyphosphate scaffolds was conducive to cell adhesion and spreading. Mouse embryonic osteoblast precursor cells and human umbilical vein endothelial cells seeded on europium-doped calcium polyphosphate scaffolds presented better proliferation and migration, especially 5% group. (4) The secretion of four growth factors (alkaline phosphatase and osteopontin, and human umbilical vein endothelial cells secreted vascular endothelial growth factor and matrix metalloproteinase 9) from co-cultured cells seeded on europium-doped calcium polyphosphate scaffolds was enhanced, which was conducive to the proliferation and differentiation of osteoblasts, especially 5% group. (5) 5% europium-doped calcium polyphosphate significantly up-regulated the ratio of osteoprotegerin/nuclear factor kappa B receptor activator ligand from osteoblast so that it had a potential efficacy to inhibit bone resorption, thus acted as an effect of alleviating aseptic loosening. (6) The above results show that the 5% europium-doped calcium polyphosphate scaffold has the potential to accelerate angiogenesis/osteogenesis and inhibit bone resorption, which is a promising multifunctional biomaterial. 

Key words: bone repair materials, europium-doped calcium polyphosphate, biocompatibility, osteogenesis, angiogenesis, aseptic loosening