In osteoporosis research, strontium ions (Sr 2+ ) have emerged as promising therapeutic agent in modified bone cements for better fracture healing. Modeling of Sr 2+ dispersion in bone could be used as a predictive tool for the evaluation of functionalized biomaterials in future. Therefore, determination of experimental parameters for Sr 2+ transport in bone is essential. In this study, we focus on the determination of Sr 2+ diffusion in viscous bovine bone marrow by time-of-flight secondary ion mass spectrometry (ToF-SIMS).Methods: 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 timedependent experimental series. Furthermore, 2D and 3D mass spectrometric imaging analysis was used to study Sr 2+ surface and bulk distribution within bovine bone marrow.Results: Detailed 2D and 3D mass spectrometric imaging analysis revealed that Sr 2+ diffusion is slower in bone marrow areas with high intensity of lipid and fatty acid signals than in areas with less lipid content. The Sr 2+ transport within this passive model can be described by Fickian diffusion. Average diffusion coefficients of Sr 2+ in bovine bone marrow were obtained from diffusion profiles in FD areas (D bovine,FD = [2.09 ± 2.39]Á10 À9 cm 2 s À1 ), slow diffusion areas (D bovine,SD = [1.52 ± 1.80]Á10 À10 cm 2 s À1 ), and total area diffusion (D bovine,TA = [1.94 ± 2.40]Á10 À9 cm 2 s À1 ). Conclusions: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 Sr 2+ diffusion in bovine bone marrow.

Next-generation bone implants will be functionalized with drugs for stimulating bone growth. Modelling of drug release by such functionalized biomaterials and drug dispersion into bone can be used as predicting tool for biomaterials testing in future. Therefore, the determination of experimental parameters to describe and simulate drug release in bone is essential. Here, we focus on Sr 2+ transport and quantification in cortical rat bone. Sr 2+ dose-dependently stimulates bone-building osteoblasts and inhibits bone-resorbing osteoclasts. It should be preferentially applied in the case of bone fracture in the context of osteoporotic bone status. Transport properties of cortical rat bone were investigated by dipping experiments of bone sections in aqueous Sr 2+ solution followed by time-of-flight secondary ion mass spectrometry (ToF-SIMS) depth profiling. Data evaluation was carried out by fitting a suitable mathematical diffusion equation to the experimental data. An average diffusion coefficient of D = (1.68 ± 0.57) · 10 −13 cm 2 s −1 for healthy cortical bone was obtained. This value differed only slightly from the value of D = (4.30 ± 1.43) · 10 −13 cm 2 s −1 for osteoporotic cortical bone. Transmission electron microscopy investigations revealed a comparable nano- and ultrastructure for both types of bone status. Additionally, Sr 2+ -enriched mineralized collagen standards were prepared for ToF-SIMS quantification of Sr 2+ content. The obtained calibration curve was used for Sr 2+ quantification in cortical and trabecular bone in real bone sections. The results allow important insights regarding the Sr 2+ transport properties in healthy and osteoporotic bone and can ultimately be used to perform a simulation of drug release and mobility in bone.

The development and characterization of biomaterials for bone replacement in case of large defects in preconditioned bone (e.g., osteoporosis) require close cooperation of various disciplines. Of particular interest are effects observed in vitro at the cellular level and their in vivo representation in animal experiments. In the present case, the material-based alteration of the ratio of osteoblasts to osteoclasts in vitro in the context of their co-cultivation was examined and showed equivalence to the material-based stimulation of bone regeneration in a bone defect of osteoporotic rats. Gelatin-modified calcium/strontium phosphates with a Ca:Sr ratio in their precipitation solutions of 5:5 and 3:7 caused a pro-osteogenic reaction on both levels in vitro and in vivo. Stimulation of osteoblasts and inhibition of osteoclast activity were proven during culture on materials with higher strontium content. The same material caused a decrease in osteoclast activity in vitro. In vivo, a positive effect of the material with increased strontium content was observed by immunohistochemistry, e.g., by significantly increased bone volume to tissue volume ratio, increased bone morphogenetic protein-2 (BMP2) expression, and significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. In addition, material degradation and bone regeneration were examined after 6 weeks using stage scans with ToF-SIMS and µ-CT imaging. The remaining material in the defects and strontium signals, which originate from areas exceeding the defect area, indicate the incorporation of strontium ions into the surrounding mineralized tissue. Thus, the material inherent properties (release of biologically active ions, solubility and degradability, mechanical strength) directly influenced the cellular reaction in vitro and also bone regeneration in vivo. Based on this, in the future, materials might be synthesized and specifically adapted to patient-specific needs and their bone status.

The present work focuses on the application of time-of-flight secondary ion mass spectrometry (ToF-SIMS) in osteoporotic bone research. In order to demonstrate the benefit, the authors present concrete application examples of ToF-SIMS in three different areas of bone research. ToF-SIMS as a mass spectrometric imaging technique allows simultaneous visualization of mineralized and nonmineralized bone tissue as well as implanted biomaterials and bone implant interphases. In the first example, the authors show that it is possible to study the incorporation and distribution of different components released from bone filler materials into bone with a single mass spectrometric measurement. This not only enables imaging of nonstained bone cross sections but also provides further insights beyond histologically obtained information. Furthermore, they successfully identified several mass fragments as markers for newly formed cartilage tissue and growth joint in bone. Different modes of ToF-SIMS as well as different SIMS instruments (IONTOF's TOF.SIMS 5 and M6 Hybrid SIMS, Ionoptika's J105) were used to identify these mass signals and highlight the high versatility of this method. In the third part, bone structure of cortical rat bone was investigated from bone sections embedded in technovit (polymethyl methacrylate, PMMA) and compared to cryosections. In cortical bone, they were able to image different morphological features, e.g., concentric arrangement of collagen fibers in so-called osteons as well as Haversian canals and osteocytes. In summary, the study provides examples of application and shows the strength of ToF-SIMS as a promising analytical method in the field of osteoporotic bone research.

Microplastics and their effects on the environment and food chain have become increasingly important in recent years. These polymer particles, which are only few millimeters in size or smaller, accumulate in the environment and can enter the human food chain via animals that ingest them. Moreover, they can accumulate impurities such as heavy metals. Therefore, this study focuses on the indiffusion behavior of metal ions into semicrystalline polypropylene (PP) applying time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) at cryo‐conditions. Diffusion coefficients of Cu2+ and Ni2+ in PP are determined by classical SIMS depth profiling in frozen state (T <−130°C) and subsequent data analysis according to Fick's second law of diffusion. The results show that diffusion of Cu2+ ions in dry PP (DPP,Cu = [2.21 ± 0.15]·10−12 cm2/s) is faster compared to Ni2+ ion diffusion of dry PP (DPP,Ni = [4.43 ± 0.55]·10−13 cm2/s). Interestingly, the diffusion of Cu2+ ions in water‐saturated PP (DPP,H2O,Cu = [1.91 ± 0.28]·10−13 cm2/s) is slower compared to Cu2+ ion diffusion in dry PP. Furthermore, high‐lateral resolution ToF‐SIMS analysis shows that metal ions only diffuse in certain areas of PP, which are most likely amorphous.