期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms21093208
关键词
large bone defects; beta-tricalcium phosphate; strontium; NF-kappa B; VEGFR-2; bioluminescence
资金
- Interdisciplinary Centre for Clinical Research (IZKF) [T9-5, T11-3]
- RWTH University of Aachen [OPBF071]
- MSD SHARP DOHME GmbH
It was hypothesized that strontium (Sr)-doped beta-tricalcium phosphate (TCP)-based scaffolds have a positive effect on the regeneration of large bone defects (LBD). Readouts in our mice models were nuclear factor-kappa beta (NF-kappa B) activity and vascular endothelial growth factor receptor-2 (VEGFR-2) promoter activity during the healing process. A 2-mm critical-size femoral fracture was performed in transgenic NF-kappa B- and VEGFR-2-luciferase reporter mice. The fracture was filled with a 3D-printed beta-TCP scaffold with or without Sr. A bioluminescence in-vivo imaging system was used to sequentially investigate NF-kappa B and VEGFR-2 expression for two months. After sacrifice, soft and osseous tissue formation in the fracture sites was histologically examined. NF-kappa B activity increased in the beta-TCP + Sr group in the latter stage (day 40-60). VEGFR-2 activity increased in the + Sr group from days 0-15 but decreased and showed significantly less activity than the beta-TCP and non-scaffold groups from days 40-60. The new bone formation and soft tissue formation in the + Sr group were significantly higher than in the beta-TCP group, whereas the percentage of osseous tissue formation in the beta-TCP group was significantly higher than in the beta-TCP + Sr group. We analyzed longitudinal VEGFR-2 promoter activity and NF-kappa B activity profiles, as respective agents of angiogenesis and inflammation, during LBD healing. The extended inflammation phase and eventually more rapid resorption of scaffold caused by the addition of strontium accelerates temporary bridging of the fracture gaps. This finding has the potential to inform an improved treatment strategy for patients who suffer from osteoporosis.
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