Benzyloxybenzene, as a novel flexible scaffold without rigid planarity, was synthesized and evaluated as ligand toward Aβ plaques. The binding site calculated for these flexible ligands was the hydrophobic Val18_Phe20 channel on the flat surface of Aβ fiber. Structure-activity relationship analysis generated a common trend that binding affinities declined significantly from para-substituted ligands to ortho-substituted ones, which was also quantitatively illustrated by 3D-QSAR modeling. Autoradiography in vitro further confirmed the high affinities of radioiodinated ligands [125I]4, [125I]24, and [125I]22 (Ki=24.3, 49.4, and 17.6 nM, respectively). In biodistribution, [125I]4 exhibited high initial uptake and rapid washout property in the brain with brain2 min/brain60 min ratio of 16.3. The excellent in vitro and in vivo biostability of [125I]4 enhanced its potential for clinical application in SPECT imaging of Aβ plaques. This approach could also allow the design of a new generation of Aβ targeting ligands without rigid and planar framework.

This study describes an effective strategy to improve pharmacokinetics of Aβ imaging agents, offering a novel class of (R)- and (S)-F-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward Aβ aggregates with K values ranging from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution, and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20. Notably, (S)-[F]28 possessed high binding potency (K = 7.6 nM) and exceptional brain kinetics (9.46% ID/g at 2 min, brain/brain = 27.8) that is superior to well-established [F]AV45. The excellent pharmacokinetics and low nonspecific binding of (S)-[F]28 were testified by dynamic PET/CT scans in monkey brains. In addition, (S)-[F]28 clearly labeled Aβ plaques both in vitro and ex vivo. These results might qualify (S)-[F]28 to detect Aβ plaques with high signal-to-noise ratio.

3D cell printing of gingival fibroblast/acellular dermal matrix/gelatin–sodium alginate scaffolds showed satisfactory biological properties.

Background Stress concentration may cause bone resorption even lead to the failure of implantation. This study was designed to investigate whether a certain sagittal root position could cause stress concentration around maxillary anterior custom-made root-analogue implants via three-dimensional finite element analysis. Methods The von Mises stresses in the bone around implants in different groups were compared by finite element analysis. Six models were constructed and divided into two groups through Geomagic Studio 2012 software. The smooth group included models of unthreaded custom-made implants in Class I, II or III sagittal root positions. The threaded group included models of reverse buttress-threaded implants in the three positions. The von Mises stress distributions and the range of the stresses under vertical and oblique loads of 100 N were analyzed through ANSYS 16.0 software. Results Stress concentrations around the labial lamella area were more prominent in the Class I position than in the Class II and Class III positions under oblique loading. Under vertical loading, the most obvious stress concentration areas were the labial lamella and palatal apical areas in the Class I and Class III positions, respectively. Stress was relatively distributed in the labial and palatal lamellae in the Class II position. The maximum von Mises stresses in the bone around the custom-made root-analogue implants in this study were lower than around traditional implants reported in the literature. The maximum von Mises stresses in this study were all less than 25 MPa in cortical bone and less than 6 MPa in cancellous bone. Additionally, compared to the smooth group, the threaded group showed lower von Mises stress concentration in the bone around the implants. Conclusions The sagittal root position affected the von Mises stress distribution around custom-made root-analogue implants. There was no certain sagittal root position that could cause excessive stress concentration around the custom-made root-analogue implants. Among the three sagittal root positions, the Class II position would be the most appropriate site for custom-made root-analogue implants.