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Objectives To test the hypotheses that (a) the chairside/handheld dental scanner combined with a metrology software will measure clinical wear in vivo in agreement with measurements from X‐ray computed microtomography and; (b) polished monolithic zirconia does not cause accelerated wear of opposing enamel. Materials and methods Thirty single crowns were randomized to receive a monolithic zirconia or metal‐ceramic crown. Two non‐restored opposing teeth in the same quadrants were identified to serve as enamel controls. After cementation, quadrants were scanned using an intraoral dental scanner. Patients were recalled at 6‐months and 1‐year for re‐scanning. Scanned images were compared using a metrology software to determine maximum vertical wear of teeth. The accuracy of the scanning measurements from this new method was compared with X‐ray computed microtomography (micro‐CT) measurements. Statistical analysis was performed using Mann–Whitney U test to determine significant differences between wear of enamel against zirconia, metal‐ceramic or enamel. Linear regression analysis determined agreement between measurements obtained using intraoral scanning and micro‐CT. Results Regression analysis demonstrated that there is a quantitative agreement between depth and volume measurements produced using intraoral scanning and the micro‐CT methodologies. There was no significant difference between the wear of enamel against polished monolithic zirconia crowns and enamel against enamel. Conclusions Intraoral scanning combined with a matching software can accurately quantify clinical wear to verify that monolithic zirconia exhibited comparable wear of enamel compared with metal‐ceramic crowns and control enamel. Agreement between the intraoral scanner and the micro‐CT was 99.8%. Clinical Trials.gov NCT02289781.

Background Brainstem gliomas are aggressive and difficult to treat. Growth of these tumors may be characterized with MRI methods. Purpose To visualize longitudinal changes in tumor volume, vascular leakiness, and tissue microstructure in an animal model of brainstem glioma. Study type Prospective animal model. Animal model Male Sprague-Dawley rats (n = 9) were imaged with 9L gliosarcoma cells infused into the pontine reticular formation of the brainstem. The MRI tumor microenvironment was studied at 3 and 10 days postimplantation of tumor cells. Field strength/sequence Diffusion tensor imaging (DTI) and dynamic contrast-enhanced (DCE)-MRI were performed at 4.7T using spin-echo multislice echo planar imaging and gradient echo multislice imaging, respectively. Assessment Tumor leakiness was assessed by the forward volumetric transfer constant, Ktrans , estimated from DCE-MRI data. Tumor structure was evaluated with fractional anisotropy (FA) obtained from DTI. Tumor volumes, delineated by a T1 map, T2 -weighted image, FA, and DCE signal enhancement were compared. Statistical tests Changes in the assessed parameters within and across the groups (ie, rats 3 and 10 days post tumor cell implantation) were evaluated with Wilcoxon rank-sum tests. Results Day 3 tumors were visible mainly on contrast-enhanced images, while day 10 tumors were visible in both contrast-enhanced and diffusion-weighted images. Mean Ktrans at day 10 was 41% lower than at day 3 (P = 0.23). In day 10 tumors, FA was regionally lower in the tumor compared to normal tissue (P = 0.0004), and tumor volume, segmented based on FA map, was significantly smaller (P ≤ 0.05) than that obtained from other contrasts. Data conclusion Contrast-enhanced MRI was found to be more sensitive in detecting early-stage tumor boundaries than other contrasts. Areas of the tumor outlined by DCE-MRI and DTI were significantly different. Over the observed period of tumor growth, average vessel leakiness decreased with tumor progression. Level of evidence 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:1322-1332.

Novel magnetite-ammonium bisphosphonate graft ionic copolymer nanocomplexes (MGICs) have been developed for potential drug delivery, magnetic resonance imaging, and hyperthermia applications. The complexes displayed relatively uniform sizes with narrow size distributions upon self-assembly in aqueous media, and their sizes were stable under simulated physiological conditions for at least 7 days. The anticancer drugs, cisplatin and carboplatin, were loaded into the complexes, and sustained release of both drugs was observed. The transverse NMR relaxivities (r2s) of the complexes were 244 s−1 (mM Fe)−1 which is fast compared to either the commercial T2-weighted MRI agent Feridex IV® or our previously reported magnetite-block ionomer complexes. Phantom MRI images of the complexes demonstrated excellent negative contrast effects of such complexes. Thus, the bisphosphonate-bearing MGICs could be promising candidates for dual drug delivery and magnetic resonance imaging. Moreover, the bisphosphonate MGICs generate heat under an alternating magnetic field of 30 kA·m−1 at 206 kHz. The temperature of the MGIC dispersion in deionized water increased from 37 to 41°C after exposure to the magnetic field for 10 minutes, corresponding to a specific absorption rate of 77.0 W·g−1. This suggests their potential as hyperthermia treatment agents as well as the possibility of temperature-dependent drug release, making MGICs more versatile in potential drug delivery applications.

Growth factors or cytokines have demonstrated the potential to alter and manipulate the biological activity of cells via binding and activation of cell surface receptors. Changes induced by cytokines can range from simple changes in the cellular motility and proliferation to more complex biological actions, such as stem-cell differentiation. Transforming growth factor beta (TGF-β) exhibits the typical functionality of a growth factor, as it is pleiotropic and causes myriad responses in a number of cell types. This multifunctional nature gives the TGF-β a great potential for therapeutic applicationsparticularly in regenerative medicine. However, this multifunctionality till now has limited its usage in vivo, since upon injection, the cytokine may activate nefarious signaling pathways, such as those associated with tumor formation. In addition to this problem, the short half-lives of cytokines also places constraints on their delivery, as the majority of the injected biomolecule will not have a sufficient biological lifetime to reach the desired target location. Therefore, the methods of targeting the growth factors to specific sites in the body will prove crucial to their successful clinical implementation. Here, we describe a novel growth-factor targeting and activation strategy based on the delivery of energy from external alternating magnetic fields to magnetic nanoparticles to which a latent TGF-β has been conjugated. We demonstrate the successful conjugation of a latent TGF-β to the surface of poly(ethylene glycol)-coated iron oxide nanoparticles, and subsequent triggered release of an active TGF-β from its latent complex on the application of an external radio frequency magnetic field. This preliminary study highlights the potential of magnetic activation to remotely control the TGF-β activity in vivo, reducing the dangerous off-target side effects and offering a path to clinical implementation of this growth factor for regenerative medicine applications.

It is currently believed that magnetic nanoparticle heaters (MNHs) can kill cancer cells only when the temperature is raised above 43 °C due to energy dissipation in an alternating magnetic field. On the other hand, simple heat conduction arguments indicate that in small tumors or single cells the relative rates of energy dissipation and heat conduction result in a negligible temperature rise, thus limiting the potential of MNHs in treating small tumors and metastatic cancer. Here we demonstrate that internalized MNHs conjugated to epidermal growth factor (EGF) and which target the epidermal growth factor receptor (EGFR) do result in a significant (up to 99.9%) reduction in cell viability and clonogenic survival in a thermal heat dose dependent manner, without the need for a perceptible temperature rise. The effect appears to be cell type specific and indicates that magnetic nanoparticles in alternating magnetic fields may effectively kill cancer cells under conditions previously considered as not possible.