The canonical Wnt/β-catenin signaling pathway is crucial for reparative dentinogenesis following tooth damage, and the modulation of this pathway affects the rate and extent of reparative dentine formation in damaged mice molars by triggering the natural process of dentinogenesis. Pharmacological stimulation of Wnt/β-catenin signaling activity by small-molecule GSK-3 inhibitor drugs following pulp exposure in mouse molars results in reparative dentinogenesis. The creation of similar but larger lesions in rat molars shows that the adenosine triphosphate (ATP)–competitive GSK-3 inhibitor, CHIR99021 (CHIR), and the ATP noncompetitive inhibitor, Tideglusib (TG), can equally enhance reparative dentine formation to fully repair an area of dentine damage up to 10 times larger, mimicking the size of small lesions in humans. To assess the chemical composition of this newly formed dentine and to compare its structure with surrounding native dentine and alveolar bone, Raman microspectroscopy analysis is used. We show that the newly formed dentine comprises equal carbonate to phosphate ratios and mineral to matrix ratios to that of native dentine, both being significantly different from bone. For an effective dentine repair, the activity of the drugs needs to be restricted to the region of damage. To investigate the range of drug-induced Wnt-activity within the dental pulp, RNA of short-term induced (24-h) molars is extracted from separated roots and crowns, and quantitative Axin2 expression is assayed. We show that the activation of Wnt/β-catenin signaling is highly restricted to pulp cells in the immediate location of the damage in the coronal pulp tissue with no drug action detected in the root pulp. These results provide further evidence that this simple method of enhancement of natural reparative dentinogenesis has the potential to be translated into a clinical direct capping approach.
Minimally invasive surgical procedures aiming to repair damaged maxillofacial tissues are hampered by its small, complex structures and difficult surgical access. Indeed, while arthroscopic procedures that deliver regenerative materials and/or cells are common in articulating joints such as the knee, there are currently no treatments that surgically place cells, regenerative factors or materials into maxillofacial tissues to foster bone, cartilage or muscle repair. Here, hyaluronic acid (HA)‐based hydrogels are developed, which are suitable for use in minimally invasive procedures, that can adhere to the surrounding tissue, and deliver cells and potentially drugs. By modifying HA with both methacrylate (MA) and 3,4‐dihydroxyphenylalanine (Dopa) groups using a completely aqueous synthesis route, it is shown that MA‐HA‐Dopa hydrogels can be applied under aqueous conditions, gel quickly using a standard surgical light, and adhere to tissue. Moreover, upon oxidation of the Dopa, human marrow stromal cells attach to hydrogels and survive when encapsulated within them. These observations show that when incorporated into HA‐based hydrogels, Dopa moieties can foster cell and tissue interactions, ensuring surgical placement and potentially enabling delivery/recruitment of regenerative cells. The findings suggest that MA‐HA‐Dopa hydrogels may find use in minimally invasive procedures to foster maxillofacial tissue repair.
The widespread use of transparent conductive films in modern display and solar technologies calls for engineering solutions with tunable light transmission and electrical characteristics. Currently, considerable effort is put into the optimization of indium tin oxide, carbon nanotube-based, metal grid, and nano-wire thin-films. The indium and carbon films do not match the chemical stability nor the electrical performance of the noble metals, and many metal films are not uniform in material distribution leading to significant surface roughness and randomized transmission haze. We demonstrate solution-processed masks for physical vapor-deposited metal electrodes consisting of hexagonally ordered aperture arrays with scalable aperture-size and spacing in an otherwise homogeneous noble metal thin-film that may exhibit better electrical performance than carbon nanotube-based thin-films for equivalent optical transparency. The fabricated electrodes are characterized optically and electrically by measuring transmittance and sheet resistance. The presented methods yield large-scale reproducible results. Experimentally realized thin-films with very low sheet resistance, R sh = 2.01 ± 0.14 Ω/sq, and transmittance, T = 25.7 ± 0.08 %, show good agreement with finite-element method simulations and an analytical model of sheet resistance in thin-films with ordered apertures support the experimental results and also serve to aid the design of highly transparent conductive films. A maximum Haacke number for these 33 nm thin-films, φ H = 10.7 × 10 −3 Ω −1 corresponding to T 80 % and R sh 10 Ω/sq, is extrapolated from the theoretical results. Increased transparency may be realizable using thinner metal films trading off conductivity. Nevertheless, the findings of this article indicate that colloidal lithographic patterned transparent conductive films can serve as vital components in technologies with a demand for transparent electrodes with low sheet resistance.
Falcarindiol (FaDOH) is a cytotoxic and anti-inflammatory polyacetylenic oxylipin found in food plants of the carrot family (Apiaceae). FaDOH has been shown to activate PPARγ and to increase the expression of the cholesterol transporter ABCA1 in cells, both of which play an important role in lipid metabolism. Thus, a common mechanism of action of the anticancer and antidiabetic properties of FaDOH may be due to a possible effect on lipid metabolism. In this study, the effect of sub-toxic concentration (5 μM) of FaDOH inside human mesenchymal stem cells (hMSCs) was studied using white light microscopy and Raman imaging. Our results show that FaDOH increases lipid content in the hMSCs cells as well as the number of lipid droplets (LDs) and that this can be explained by increased expression of PPARγ2 as shown in human colon adenocarcinoma cells. Activation of PPARγ can lead to increased expression of ABCA1. We demonstrate that ABCA1 is upregulated in colorectal neoplastic rat tissue, which indicates a possible role of this transporter in the redistribution of lipids and increased formation of LDs in cancer cells that may lead to endoplasmic reticulum stress and cancer cell death.
Hydrogels are widely used as mimics of the native extracellular matrix as their physical and biological properties can be tuned over a wide range to match those of the native...
M. (2018). Structural basis for a naphthyl end-capped oligothiophene with embedded metallic nanoparticles for organic field-effect transistors. Applied Physics Letters, 113(25), [251903]. https://doi.
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