Angiogenesis in bone tissue engineering via ceramic scaffolds: A review of concepts and recent advancements.

Due to organ donor shortages, long transplant waitlists, and the complications/limitations associated with auto and allotransplantation, biomaterials and tissue-engineered models are gaining attention as feasible alternatives for replacing and reconstructing damaged organs and tissues. Among various tissue engineering applications, bone tissue engineering has become a promising strategy to replace or repair damaged bone. We aimed to provide an overview of bioactive ceramic scaffolds in bone tissue engineering, focusing on angiogenesis and the effect of different biofunctionalization strategies. Different routes to angiogenesis, including chemical induction through signaling molecules immobilized covalently or non-covalently, in situ secretion of angiogenic growth factors, and the degradation of inorganic scaffolds, are described. Physical induction mechanisms are also discussed, followed by a review of methods for fabricating bioactive ceramic scaffolds via microfabrication methods, such as photolithography and 3D printing. Finally, the strengths and weaknesses of the commonly used methodologies and future directions are discussed.

Iterative nanoparticle bioengineering enabled by x-ray fluorescence imaging.

Nanoparticles (NPs) are currently developed for drug delivery and molecular imaging. However, they often get intercepted before reaching their target, leading to low targeting efficacy and signal-to-noise ratio. They tend to accumulate in organs like lungs, liver, kidneys, and spleen. The remedy is to iteratively engineer NP surface properties and administration strategies, presently a time-consuming process that includes organ dissection at different time points. To improve this, we propose a rapid iterative approach using whole-animal x-ray fluorescence (XRF) imaging to systematically evaluate NP distribution in vivo. We applied this method to molybdenum-based NPs and clodronate liposomes for tumor targeting with transient macrophage depletion, leading to reduced accumulations in lungs and liver and eventual tumor detection. XRF computed tomography (XFCT) provided 3D insight into NP distribution within the tumor. We validated the results using a multiscale imaging approach with dye-doped NPs and gene expression analysis for nanotoxicological profiling. XRF imaging holds potential for advancing therapeutics and diagnostics in preclinical pharmacokinetic studies.

Laboratory Liquid-Jet X-ray Microscopy and X-ray Fluorescence Imaging for Biomedical Applications.

Diffraction-limited resolution and low penetration depth are fundamental constraints in optical microscopy and in vivo imaging. Recently, liquid-jet X-ray technology has enabled the generation of X-rays with high-power intensities in laboratory settings. By allowing the observation of cellular processes in their natural state, liquid-jet soft X-ray microscopy (SXM) can provide morphological information on living cells without staining. Furthermore, X-ray fluorescence imaging (XFI) permits the tracking of contrast agents in vivo with high elemental specificity, going beyond attenuation contrast. In this study, we established a methodology to investigate nanoparticle (NP) interactions in vitro and in vivo, solely based on X-ray imaging. We employed soft (0.5 keV) and hard (24 keV) X-rays for cellular studies and preclinical evaluations, respectively. Our results demonstrated the possibility of localizing NPs in the intracellular environment via SXM and evaluating their biodistribution with in vivo multiplexed XFI. We envisage that laboratory liquid-jet X-ray technology will significantly contribute to advancing our understanding of biological systems in the field of nanomedical research.

Magnetically-assisted viral transduction (magnetofection) medical applications: An update.

Gene therapy involves replacing a faulty gene or adding a new gene inside the body's cells to cure disease or improve the body's ability to fight disease. Its popularity is evident from emerging concepts such as CRISPR-based genome editing and epigenetic studies and has been moved to a clinical setting. The strategy for therapeutic gene design includes; suppressing the expression of pathogenic genes, enhancing necessary protein production, and stimulating the immune system, which can be incorporated into both viral and non-viral gene vectors. Although non-viral gene delivery provides a safer platform, it suffers from an inefficient rate of gene transfection, which means a few genes could be successfully transfected and expressed within the cells. Incorporating nucleic acids into the viruses and using these viral vectors to infect cells increases gene transfection efficiency. Consequently, more cells will respond, more genes will be expressed, and sustained and successful gene therapy can be achieved. Combining nanoparticles (NPs) and nucleic acids protects genetic materials from enzymatic degradation. Furthermore, the vectors can be transferred faster, facilitating cell attachment and cellular uptake. Magnetically assisted viral transduction (magnetofection) enhances gene therapy efficiency by mixing magnetic nanoparticles (MNPs) with gene vectors and exerting a magnetic field to guide a significant number of vectors directly onto the cells. This research critically reviews the MNPs and the physiochemical properties needed to assemble an appropriate magnetic viral vector, discussing cellular hurdles and attitudes toward overcoming these barriers to reach clinical gene therapy perspectives. We focus on the studies conducted on the various applications of magnetic viral vectors in cancer therapies, regenerative medicine, tissue engineering, cell sorting, and virus isolation.

Two-Photon Polymerization Printing with High Metal Nanoparticle Loading.

Two-photon polymerization (2PP) is an efficient technique to achieve high-resolution, three-dimensional (3D)-printed complex structures. However, it is restricted to photocurable monomer combinations, thus presenting constraints when aiming at attaining functionally active resist formulations and structures. In this context, metal nanoparticle (NP) integration as an additive can enable functionality and pave the way to more dedicated applications. Challenges lay on the maximum NP concentrations that can be incorporated into photocurable resist formulations due to the laser-triggered interactions, which primarily originate from laser scattering and absorption, as well as the limited dispersibility threshold. In this study, we propose an approach to address these two constraints by integrating metallic Rh NPs formed ex situ, purposely designed for this scope. The absence of surface plasmon resonance (SPR) within the visible and near-infrared spectra, coupled with the limited absorption value measured at the laser operating wavelength (780 nm), significantly limits the laser-induced interactions. Moreover, the dispersibility threshold is increased by engineering the NP surface to be compatible with the photocurable resin, permitting us to achieve concentrations of up to 2 wt %, which, to our knowledge, is significantly higher than the previously reported limit (or threshold) for embedded metal NPs. Another distinctive advantage of employing Rh NPs is their role as promising contrast agents for X-ray fluorescence (XRF) bioimaging. We demonstrated the presence of Rh NPs within the whole 2PP-printed structure and emphasized the potential use of NP-loaded 3D-printed nanostructures for medical devices.

Organ uptake, toxicity and skin clearance of ruthenium contrast agents monitored in vivo by x-ray fluorescence.

Aims: To investigate the distribution and toxicity of ruthenium nanoparticles (Ru NPs) injected intravenously in mice. Methods: We synthesized Ru NPs, followed their biodistribution by x-ray fluorescence (XRF) imaging and evaluated organ toxicity by histopathology and gene expression. Results: Ru NPs accumulated, mainly in liver and spleen, where they were phagocyted by tissue macrophages, giving a transient inflammation and oxidative stress response that declined after 2 weeks. Ru NPs gradually accumulated in the skin, which was confirmed by microscopic examination of skin biopsies. Conclusion: Ru NP toxicity in recipient organs is transient. Particles are at least partially excreted by the skin, supporting a role for the skin as a nanoparticle clearing organ.

Silver nanoparticles with excellent biocompatibility block pseudotyped SARS-CoV-2 in the presence of lung surfactant.

Silver (Ag) is known to possess antimicrobial properties which is commonly attributed to soluble Ag ions. Here, we showed that Ag nanoparticles (NPs) potently inhibited SARS-CoV-2 infection using two different pseudovirus neutralization assays. We also evaluated a set of Ag nanoparticles of different sizes with varying surface properties, including polyvinylpyrrolidone (PVP)-coated and poly (ethylene glycol) (PEG)-modified Ag nanoparticles, and found that only the bare (unmodified) nanoparticles were able to prevent virus infection. For comparison, TiO2 nanoparticles failed to intercept the virus. Proteins and lipids may adsorb to nanoparticles forming a so-called bio-corona; however, Ag nanoparticles pre-incubated with pulmonary surfactant retained their ability to block virus infection in the present model. Furthermore, the secondary structure of the spike protein of SARS-CoV-2 was perturbed by the Ag nanoparticles, but not by the ionic control (AgNO3) nor by the TiO2 nanoparticles. Finally, Ag nanoparticles were shown to be non-cytotoxic towards the human lung epithelial cell line BEAS-2B and this was confirmed by using primary human nasal epithelial cells. These results further support that Ag nanoparticles may find use as anti-viral agents.

Thermoelectric Inks and Power Factor Tunability in Hybrid Films through All Solution Process.

Thermoelectric (TE) materials can have a strong benefit to harvest thermal energy if they can be applied to large areas without losing their performance over time. One way of achieving large-area films is through hybrid materials, where a blend of TE materials with polymers can be applied as coating. Here, we present the development of all solution-processed TE ink and hybrid films with varying contents of TE Sb2Te3 and Bi2Te3 nanomaterials, along with their characterization. Using (1-methoxy-2-propyl) acetate (MPA) as the solvent and poly (methyl methacrylate) as the durable polymer, large-area homogeneous hybrid TE films have been fabricated. The conductivity and TE power factor improve with nanoparticle volume fraction, peaking around 60-70% solid material fill factor. For larger fill factors, the conductivity drops, possibly because of an increase in the interface resistance through interface defects and reduced connectivity between the platelets in the medium. The use of dodecanethiol (DDT) as an additive in the ink formulation enabled an improvement in the electrical conductivity through modification of interfaces and the compactness of the resultant films, leading to a 4-5 times increase in the power factor for both p- and n-type hybrid TE films, respectively. The observed trends were captured by combining percolation theory with analytical resistive theory, with the above assumption of increasing interface resistance and connectivity with polymer volume reduction. The results obtained on these hybrid films open a new low-cost route to produce and implement TE coatings on a large scale, which can be ideal for driving flexible, large-area energy scavenging technologies such as personal medical devices and the IoT.

Modulation of Conductivity of Alginate Hydrogels Containing Reduced Graphene Oxide through the Addition of Proteins.

Modifying hydrogels in order to enhance their conductivity is an exciting field with applications in cardio and neuro-regenerative medicine. Therefore, we have designed hybrid alginate hydrogels containing uncoated and protein-coated reduced graphene oxide (rGO). We specifically studied the adsorption of three different proteins, BSA, elastin, and collagen, and the outcomes when these protein-coated rGO nanocomposites are embedded within the hydrogels. Our results demonstrate that BSA, elastin, and collagen are adsorbed onto the rGO surface, through a non-spontaneous phenomenon that fits Langmuir and pseudo-second-order adsorption models. Protein-coated rGOs are able to preclude further adsorption of erythropoietin, but not insulin. Collagen showed better adsorption capacity than BSA and elastin due to its hydrophobic nature, although requiring more energy. Moreover, collagen-coated rGO hybrid alginate hydrogels showed an enhancement in conductivity, showing that it could be a promising conductive scaffold for regenerative medicine.

Carbon Quantum Dots Conjugated Rhodium Nanoparticles as Hybrid Multimodal Contrast Agents.

Nanoparticle (NP)-based contrast agents enabling different imaging modalities are sought for non-invasive bio-diagnostics. A hybrid material, combining optical and X-ray fluorescence is presented as a bioimaging contrast agent. Core NPs based on metallic rhodium (Rh) have been demonstrated to be potential X-ray Fluorescence Computed Tomography (XFCT) contrast agents. Microwave-assisted hydrothermal method is used for NP synthesis, yielding large-scale NPs within a significantly short reaction time. Rh NP synthesis is performed by using a custom designed sugar ligand (LODAN), constituting a strong reducing agent in aqueous solution, which yields NPs with primary amines as surface functional groups. The amino groups on Rh NPs are used to directly conjugate excitation-independent nitrogen-doped carbon quantum dots (CQDs), which are synthesized through citrate pyrolysis in ammonia solution. CQDs provided the Rh NPs with optical fluorescence properties and improved their biocompatibility, as demonstrated in vitro by Real-Time Cell Analysis (RTCA) on a macrophage cell line (RAW 264.7). The multimodal characteristics of the hybrid NPs are confirmed with confocal microscopy, and X-ray Fluorescence (XRF) phantom experiments.

Minute-Made, High-Efficiency Nanostructured Bi2Te3 via High-Throughput Green Solution Chemical Synthesis.

Scalable synthetic strategies for high-quality and reproducible thermoelectric (TE) materials is an essential step for advancing the TE technology. We present here very rapid and effective methods for the synthesis of nanostructured bismuth telluride materials with promising TE performance. The methodology is based on an effective volume heating using microwaves, leading to highly crystalline nanostructured powders, in a reaction duration of two minutes. As the solvents, we demonstrate that water with a high dielectric constant is as good a solvent as ethylene glycol (EG) for the synthetic process, providing a greener reaction media. Crystal structure, crystallinity, morphology, microstructure and surface chemistry of these materials were evaluated using XRD, SEM/TEM, XPS and zeta potential characterization techniques. Nanostructured particles with hexagonal platelet morphology were observed in both systems. Surfaces show various degrees of oxidation, and signatures of the precursors used. Thermoelectric transport properties were evaluated using electrical conductivity, Seebeck coefficient and thermal conductivity measurements to estimate the TE figure-of-merit, ZT. Low thermal conductivity values were obtained, mainly due to the increased density of boundaries via materials nanostructuring. The estimated ZT values of 0.8-0.9 was reached in the 300-375 K temperature range for the hydrothermally synthesized sample, while 0.9-1 was reached in the 425-525 K temperature range for the polyol (EG) sample. Considering the energy and time efficiency of the synthetic processes developed in this work, these are rather promising ZT values paving the way for a wider impact of these strategic materials with a minimum environmental impact.

Investigation of the Heteroepitaxial Process Optimization of Ge Layers on Si (001) by RPCVD.

This work presents the growth of high-quality Ge epilayers on Si (001) substrates using a reduced pressure chemical vapor deposition (RPCVD) chamber. Based on the initial nucleation, a low temperature high temperature (LT-HT) two-step approach, we systematically investigate the nucleation time and surface topography, influence of a LT-Ge buffer layer thickness, a HT-Ge growth temperature, layer thickness, and high temperature thermal treatment on the morphological and crystalline quality of the Ge epilayers. It is also a unique study in the initial growth of Ge epitaxy; the start point of the experiments includes Stranski-Krastanov mode in which the Ge wet layer is initially formed and later the growth is developed to form nuclides. Afterwards, a two-dimensional Ge layer is formed from the coalescing of the nuclides. The evolution of the strain from the beginning stage of the growth up to the full Ge layer has been investigated. Material characterization results show that Ge epilayer with 400 nm LT-Ge buffer layer features at least the root mean square (RMS) value and it's threading dislocation density (TDD) decreases by a factor of 2. In view of the 400 nm LT-Ge buffer layer, the 1000 nm Ge epilayer with HT-Ge growth temperature of 650 °C showed the best material quality, which is conducive to the merging of the crystals into a connected structure eventually forming a continuous and two-dimensional film. After increasing the thickness of Ge layer from 900 nm to 2000 nm, Ge surface roughness decreased first and then increased slowly (the RMS value for 1400 nm Ge layer was 0.81 nm). Finally, a high-temperature annealing process was carried out and high-quality Ge layer was obtained (TDD=2.78 × 107 cm-2). In addition, room temperature strong photoluminescence (PL) peak intensity and narrow full width at half maximum (11 meV) spectra further confirm the high crystalline quality of the Ge layer manufactured by this optimized process. This work highlights the inducing, increasing, and relaxing of the strain in the Ge buffer and the signature of the defect formation.

Quantitative conversion of biomass in giant DNA virus infection.

Bioconversion of organic materials is the foundation of many applications in chemical engineering, microbiology and biochemistry. Herein, we introduce a new methodology to quantitatively determine conversion of biomass in viral infections while simultaneously imaging morphological changes of the host cell. As proof of concept, the viral replication of an unidentified giant DNA virus and the cellular response of an amoebal host are studied using soft X-ray microscopy, titration dilution measurements and thermal gravimetric analysis. We find that virions produced inside the cell are visible from 18 h post infection and their numbers increase gradually to a burst size of 280-660 virions. Due to the large size of the virion and its strong X-ray absorption contrast, we estimate that the burst size corresponds to a conversion of 6-12% of carbonaceous biomass from amoebal host to virus. The occurrence of virion production correlates with the appearance of a possible viral factory and morphological changes in the phagosomes and contractile vacuole complex of the amoeba, whereas the nucleus and nucleolus appear unaffected throughout most of the replication cycle.

Optical and X-ray Fluorescent Nanoparticles for Dual Mode Bioimaging.

Nanoparticle (NP) based contrast agents detectable via different imaging modalities (multimodal properties) provide a promising strategy for noninvasive diagnostics. Core-shell NPs combining optical and X-ray fluorescence properties as bioimaging contrast agents are presented. NPs developed earlier for X-ray fluorescence computed tomography (XFCT), based on ceramic molybdenum oxide (MoO2) and metallic rhodium (Rh) and ruthenium (Ru), are coated with a silica (SiO2) shell, using ethanolamine as the catalyst. The SiO2 coating method introduced here is demonstrated to be applicable to both metallic and ceramic NPs. Furthermore, a fluorophore (Cy5.5 dye) was conjugated to the SiO2 layer, without altering the morphological and size characteristics of the hybrid NPs, rendering them with optical fluorescence properties. The improved biocompatibility of the SiO2 coated NPs without and with Cy5.5 is demonstrated in vitro by Real-Time Cell Analysis (RTCA) on a macrophage cell line (RAW 264.7). The multimodal characteristics of the core-shell NPs are confirmed with confocal microscopy, allowing the intracellular localization of these NPs in vitro to be tracked and studied. In situ XFCT successfully showed the possibility of in vivo multiplexed bioimaging for multitargeting studies with minimum radiation dose. Combined optical and X-ray fluorescence properties empower these NPs as effective macroscopic and microscopic imaging tools.

Recent advances in the modification of carbon-based quantum dots for biomedical applications.

Carbon-based quantum dots (CDs) are mainly divided into two sub-groups; carbon quantum dots (CQDs) and graphene quantum dots (GQDs), which exhibit outstanding photoluminescence (PL) properties, low toxicity, superior biocompatibility and facile functionalization. Regarding these features, they have been promising candidates for biomedical science and engineering applications. In this work, we reviewed the efforts made to modify these zero-dimensional nano-materials to obtain the best properties for bio-imaging, drug and gene delivery, cancer therapy, and bio-sensor applications. Five main surface modification techniques with outstanding results are investigated, including doping, surface functionalization, polymer capping, nano-composite and core-shell structures, and the drawbacks and challenges in each of these methods are discussed.

Synthesis, Physicochemical Characterization, and Cytotoxicity Assessment of Rh Nanoparticles with Different Morphologies-as Potential XFCT Nanoprobes.

Morphologically controllable synthesis of Rh nanoparticles (NPs) was achieved by the use of additives during polyol synthesis. The effect of salts and surfactant additives including PVP, sodium acetate, sodium citrate, CTAB, CTAC, and potassium bromide on Rh NPs morphology was investigated. When PVP was used as the only additive, trigonal NPs were obtained. Additives containing Br- ions (CTAB and KBr) resulted in NPs with a cubic morphology, while those with carboxyl groups (sodium citrate and acetate) formed spheroid NPs. The use of Cl- ions (CTAC) resulted in a mixture of polygon morphologies. Cytotoxicity of these NPs was evaluated on macrophages and ovarian cancer cell lines. Membrane integrity and cellular activity are both influenced to a similar extent, for both the cell lines, with respect to the morphology of Rh NPs. The cells exposed to trigonal Rh NPs showed the highest viability, among the NP series. Particles with a mixed polygon morphology had the highest cytotoxic impact, followed by cubic and spherical NPs. The Rh NPs were further demonstrated as contrast agents for X-ray fluorescence computed tomography (XFCT) in a small-animal imaging setting. This work provides a detailed route for the synthesis, morphology control, and characterization of Rh NPs as viable contrast agents for XFCT bio-imaging.

Nitric oxide-dependent biodegradation of graphene oxide reduces inflammation in the gastrointestinal tract.

Understanding the biological fate of graphene-based materials such as graphene oxide (GO) is crucial to assess adverse effects following intentional or inadvertent exposure. Here we provide first evidence of biodegradation of GO in the gastrointestinal tract using zebrafish as a model. Raman mapping was deployed to assess biodegradation. The degradation was blocked upon knockdown of nos2a encoding the inducible nitric oxide synthase (iNOS) or by pharmacological inhibition of NOS using l-NAME, demonstrating that the process was nitric oxide (NO)-dependent. NO-dependent degradation of GO was further confirmed in vitro by combining a superoxide-generating system, xanthine/xanthine oxidase (X/XO), with an NO donor (PAPA NONOate), or by simultaneously producing superoxide and NO by decomposition of SIN-1. Finally, by using the transgenic strain Tg(mpx:eGFP) to visualize the movement of neutrophils, we could show that inhibition of the degradation of GO resulted in increased neutrophil infiltration into the gastrointestinal tract, indicative of inflammation.

Longitudinal In-Vivo X-Ray Fluorescence Computed Tomography With Molybdenum Nanoparticles.

X-ray fluorescence computed tomography (XFCT) with nanoparticles (NPs) as contrast agents shows potential for molecular biomedical imaging with higher spatial resolution than present methods. To date the technique has been demonstrated on phantoms and mice, however, parameters such as radiation dose, exposure times and sensitivity have not yet allowed for high-spatial-resolution in vivo longitudinal imaging, i.e., imaging of the same animal at different time points. Here we show in vivo XFCT with spatial resolution in the 200- [Formula: see text] range in a proof-of-principle longitudinal study where mice are imaged five times each during an eight-week period following tail-vein injection of NPs. We rely on a 24 keV x-ray pencil-beam-based excitation of in-house-synthesized molybdenum oxide NPs (MoO2) to provide the high signal-to-background x-ray fluorescence detection necessary for XFCT imaging with low radiation dose and short exposure times. We quantify the uptake and clearance of NPs in vivo through imaging, and monitor animal well-being over the course of the study with support from histology and DNA stability analysis to assess the impact of x-ray exposure and NPs on animal welfare. We conclude that the presented imaging arrangement has potential for in vivo longitudinal studies, putting emphasis on designing biocompatible NPs as the future focus for active-targeting preclinical XFCT.

On the Effect of Modified Carbohydrates on the Size and Shape of Gold and Silver Nanostructures.

Gold (Au) and silver (Ag) nanostructures have widespread utilization from biomedicine to materials science. Therefore, their synthesis with control of their morphology and surface chemistry have been among the hot topics over the last decades. Here, we introduce a new approach relying on sugar derivatives that work as reducing, stabilizing, and capping agents in the synthesis of Au and Ag nanostructures. These sugar derivatives are utilized alone and as mixture, resulting in spherical, spheroid, trigonal, polygonic, and star-like morphologies. The synthesis approach was further tested in the presence of acetate and dimethylamine as size- and shape-directing agents. With the use of transmission electron microscopy (TEM), selected area electron diffraction (SAED), x-ray diffraction (XRD), scanning electron microscopy (SEM), and ultraviolet-visible (UV-vis) absorption spectroscopy techniques, the particle size, shape, assembly, aggregation, and film formation characteristics were evaluated. NPs' attributes were shown to be tunable by manipulating the sugar ligand selection and sugar ligand/metal-ion ratio. For instance, with an imine side group and changing the sugar moiety from cellobiose to lactose, the morphology of the Ag nanoparticles (NPs) transformed from well dispersed cubic to rough and aggregated. The introduction of acetate and dimethylamine further extended the growth pattern and morphological properties of these NPs. As examples, L5 AS, G5AS, and S5AS ligands formed spherical or sheet-like structures when used alone, which upon the use of these additives transformed into larger multicore and rough NPs, revealing their significant effect on the NP morphology. Selected samples were tested for their stability against protein corona formation and ionic strength, where a high chemical stability and resistance to protein coating were observed. The findings show a promising, benign approach for the synthesis of shape- and size-directed Au and Ag nanostructures, along with a selection of the chemistry of carbohydrate-derivatives that can open new windows for their applications.

Synthesis and Cytotoxicity Studies on Ru and Rh Nanoparticles as Potential X-Ray Fluorescence Computed Tomography (XFCT) Contrast Agents.

X-ray fluorescence computed tomography (XFCT) is an emerging biomedical imaging technique, which demands the development of new contrast agents. Ruthenium (Ru) and rhodium (Rh) have spectrally attractive Kα edge energies, qualifying them as new XFCT bio-imaging probes. Metallic Ru and Rh nanoparticles are synthesized by polyol method, in the presence of a stabilizer. The effect of several reaction parameters, including reaction temperature time, precursor and stabilizer concentration, and stabilizer molecular weight, on the size of particles, were studied. Resultant materials were characterized in detail using XRD, TEM, FT-IR, DLS-zeta potential and TGA techniques. Ru particles in the size range of 1-3 nm, and Rh particles of 6-9 nm were obtained. At physiological pH, both material systems showed agglomeration into larger assemblies ranging from 12-104 nm for Ru and 25-50 nm for Rh. Cytotoxicity of the nanoparticles (NPs) was evaluated on macrophages and ovarian cancer cells, showing minimal toxicity in doses up to 50 µg/mL. XFCT performance was evaluated on a small-animal-sized phantom model, demonstrating the possibility of quantitative evaluation of the measured dose with an expected linear response. This work provides a detailed route for the synthesis, size control and characterization of two materials systems as viable contrast agents for XFCT bio-imaging.