Determination of Sr2+ mobility in viscous bovine bone marrow by cryo-time-of-flight secondary ion mass spectrometry.

Abstract

In osteoporosis research, strontium ions (Sr2+ ) have emerged as promising therapeutic agent in modified bone cements for better fracture healing. Modeling of Sr2+ dispersion in bone could be used as a predictive tool for the evaluation of functionalized biomaterials in future. Therefore, determination of experimental parameters for Sr2+ transport in bone is essential. In this study, we focus on the determination of Sr2+ diffusion in viscous bovine bone marrow by time-of-flight secondary ion mass spectrometry (ToF-SIMS). For this comparatively fast diffusion (FD) experiment, a specific experimental protocol of ToF-SIMS depth profiling under cryogenic conditions was developed. The validity of our experimental approach is proven by a time-dependent experimental series. Furthermore, 2D and 3D mass spectrometric imaging analysis was used to study Sr2+ surface and bulk distribution within bovine bone marrow. Detailed 2D and 3D mass spectrometric imaging analysis revealed that Sr2+ diffusion is slower in bone marrow areas with high intensity of lipid and fatty acid signals than in areas with less lipid content. The Sr2+ transport within this passive model can be described by Fickian diffusion. Average diffusion coefficients of Sr2+ in bovine bone marrow were obtained from diffusion profiles in FD areas (Dbovine,FD = [2.09 ± 2.39]·10-9 cm2 s-1 ), slow diffusion areas (Dbovine,SD = [1.52 ± 1.80]·10-10 cm2 s-1 ), and total area diffusion (Dbovine,TA = [1.94 ± 2.40]·10-9 cm2 s-1 ). We were able to show that cryo-ToF-SIMS is a useful tool for the characterization of rapid diffusion in water-containing highly viscous media. To the best of our knowledge, this is the first reported experimental approach for the investigation of the distribution of low concentrated therapeutic agents in bone marrow. Overall, our results provide important insights about Sr2+ diffusion in bovine bone marrow.