scholarly journals GSK3 Inhibitor-Induced Dentinogenesis Using a Hydrogel

2021 ◽  
pp. 002203452110206
Author(s):  
A. Alaohali ◽  
C. Salzlechner ◽  
L.K. Zaugg ◽  
F. Suzano ◽  
A. Martinez ◽  
...  

Small-molecule drugs targeting glycogen synthase kinase 3 (GSK3) as inhibitors of the protein kinase activity are able to stimulate reparative dentine formation. To develop this approach into a viable clinical treatment for exposed pulp lesions, we synthesized a novel, small-molecule noncompetitive adenosine triphosphate (ATP) drug that can be incorporated into a biodegradable hydrogel for placement by syringe into the tooth. This new drug, named NP928, belongs to the thiadiazolidinone (TDZD) family and has equivalent activity to similar drugs of this family such as tideglusib. However, NP928 is more water soluble than other TDZD drugs, making it more suitable for direct delivery into pulp lesions. We have previously reported that biodegradable marine collagen sponges can successfully deliver TDZD drugs to pulp lesions, but this involves in-theater preparation of the material, which is not ideal in a clinical context. To improve surgical handling and delivery, here we incorporated NP928 into a specifically tailored hydrogel that can be placed by syringe into a damaged tooth. This hydrogel is based on biodegradable hyaluronic acid and can be gelled in situ upon dental blue light exposure, similarly to other common dental materials. NP928 released from hyaluronic acid–based hydrogels upregulated Wnt/β-catenin activity in pulp stem cells and fostered reparative dentine formation compared to marine collagen sponges delivering equivalent concentrations of NP928. This drug-hydrogel combination has the potential to be rapidly developed into a therapeutic procedure that is amenable to general dental practice.

2020 ◽  
Vol 85 (9) ◽  
pp. 1197-1221 ◽  
Author(s):  
Ilinka Mirkovic ◽  
Marija Nikolic ◽  
Sanja Ostojic ◽  
Jelena Maletaskic ◽  
Zoran Petrovic ◽  
...  

Semi-interpenetrating polymer networks (SIPN) based on thermoresponsive poly(N-isopropylacrylamide) (PNIPA) and water-soluble sodium salts of linear hyaluronic acid (Na-HA) were physically cross-linked with synthetic nanoclay (laponite XLG). PNIPA hydrogels with different cross-linking densities and Na-HA concentrations were synthesized by in situ free-radical redox polymerization. The structure and heterogeneity of the semi-IPN hydrogels were examined by SEM and XRD. The content of clay incorporated in the gel was determined by TGA. DSC measurements showed that volume phase transition temperature and its enthalpy varied with the clay and hyaluronic acid content. SIPN hydrogels containing negatively charged polyelectrolyte, Na- HA, exhibited higher Qe and faster deswelling rates than the corresponding PNIPA NC hydrogels. The presence of the anionic Na-HA polymer reduced the storage modulus, indicating a weakening of the hydrogel network structure, especially at lower clay contents. The nanocomposite hydrogels exhibited high tan ? values, which increased with increasing Na-HA content.


2018 ◽  
Author(s):  
Roshna Vakkeel ◽  
Aleeza Farrukh ◽  
Aranzazu del Campo

In order to study how dynamic changes of α5β1 integrin engagement affect cellular behaviour, photoactivatable derivatives of α5β1 specific ligands are presented in this article. The presence of the photoremovable protecting group (PRPG) introduced at a relevant position for integrin recognition, temporally inhibits ligand bioactivity. Light exposure at cell-compatible dose efficiently cleaves the PRPG and restores functionality. Selective cell response (attachment, spreading, migration) to the activated ligand on the surface is achieved upon controlled exposure. Spatial and temporal control of the cellular response is demonstrated, including the possibility to in situ activation. Photoactivatable integrin-selective ligands in model microenvironments will allow the study of cellular behavior in response to changes in the activation of individual integrins as consequence of dynamic variations of matrix composition.


Author(s):  
Ain Uddin ◽  
Weifan Sang ◽  
Yong Gao ◽  
Kyle Plunkett

The synthesis of poly(p-xylylene)s (PPXs) with sidechains containing alkyl bromide functionality, and their post-polymer modification, is described. The PPXs were prepared by a diimide hydrogenation of poly(p-phenylene vinylene)s (PPVs) that were originally synthesized by a Gilch polymerization. The polymer backbone reduction was carried out with hydrazine hydrate in toluene at 80 °C to provide polymers with the sidechain-containing bromide functionality intact. To demonstrate post-polymer modification of the sidechains, the resulting PPX polymers were modified with trimethylamine to form tetraalkylammonium ion functionality and were evaluated as anion conducting membranes. While PPX homopolymers containing tetralkylammonium ions were completely water soluble and not able to form valuable films, PPX copolymers containing mixed tetraalkylammonium ions and hydrophobic chains were capable of film formation and alkaline stability. In addition, an in situ crosslinking process that used N,N,N',N'-tetramethyl-1,6-hexanediamine during the tetraalkylammonium formation of brominated PPX polymers was also evaluated and gave reasonable films with conductivities of ~10 mS-cm-1.


2019 ◽  
Author(s):  
Ain Uddin ◽  
Weifan Sang ◽  
Yong Gao ◽  
Kyle Plunkett

The synthesis of poly(p-xylylene)s (PPXs) with sidechains containing alkyl bromide functionality, and their post-polymer modification, is described. The PPXs were prepared by a diimide hydrogenation of poly(p-phenylene vinylene)s (PPVs) that were originally synthesized by a Gilch polymerization. The polymer backbone reduction was carried out with hydrazine hydrate in toluene at 80 °C to provide polymers with the sidechain-containing bromide functionality intact. To demonstrate post-polymer modification of the sidechains, the resulting PPX polymers were modified with trimethylamine to form tetraalkylammonium ion functionality and were evaluated as anion conducting membranes. While PPX homopolymers containing tetralkylammonium ions were completely water soluble and not able to form valuable films, PPX copolymers containing mixed tetraalkylammonium ions and hydrophobic chains were capable of film formation and alkaline stability. In addition, an in situ crosslinking process that used N,N,N',N'-tetramethyl-1,6-hexanediamine during the tetraalkylammonium formation of brominated PPX polymers was also evaluated and gave reasonable films with conductivities of ~10 mS-cm-1.


2019 ◽  
Vol 43 (24) ◽  
pp. 9458-9465
Author(s):  
Xiquan Yue ◽  
Lihong Su ◽  
Xu Chen ◽  
Junfeng Liu ◽  
Longpo Zheng ◽  
...  

The strategy is based on small molecule-mediated hybridization chain reaction.


2021 ◽  
Vol 7 (2) ◽  
pp. eabe3097
Author(s):  
Hongwei Sheng ◽  
Jingjing Zhou ◽  
Bo Li ◽  
Yuhang He ◽  
Xuetao Zhang ◽  
...  

It has been an outstanding challenge to achieve implantable energy modules that are mechanically soft (compatible with soft organs and tissues), have compact form factors, and are biodegradable (present for a desired time frame to power biodegradable, implantable medical electronics). Here, we present a fully biodegradable and bioabsorbable high-performance supercapacitor implant, which is lightweight and has a thin structure, mechanical flexibility, tunable degradation duration, and biocompatibility. The supercapacitor with a high areal capacitance (112.5 mF cm−2 at 1 mA cm−2) and energy density (15.64 μWh cm−2) uses two-dimensional, amorphous molybdenum oxide (MoOx) flakes as electrodes, which are grown in situ on water-soluble Mo foil using a green electrochemical strategy. Biodegradation behaviors and biocompatibility of the associated materials and the supercapacitor implant are systematically studied. Demonstrations of a supercapacitor implant that powers several electronic devices and that is completely degraded after implantation and absorbed in rat body shed light on its potential uses.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 637
Author(s):  
Nicholas S. Moore ◽  
Robert A. Mans ◽  
Mackenzee K. McCauley ◽  
Colton S. Allgood ◽  
Keri A. Barksdale

Evidence from human and animal studies indicate that disrupted light cycles leads to alterations of the sleep state, poor cognition, and the risk of developing neuroinflammatory and generalized health disorders. Zebrafish exhibit a diurnal circadian rhythm and are an increasingly popular model in studies of neurophysiology and neuropathophysiology. Here, we investigate the effect of alterations in light cycle on the adult zebrafish brain: we measured the effect of altered, unpredictable light exposure in adult zebrafish telencephalon, homologous to mammalian hippocampus, and the optic tectum, a significant visual processing center with extensive telencephalon connections. The expression of heat shock protein-70 (HSP70), an important cell stress mediator, was significantly decreased in optic tectum of adult zebrafish brain following four days of altered light exposure. Further, pSer473-Akt (protein kinase B) was significantly reduced in telencephalon following light cycle alteration, and pSer9-GSK3β (glycogen synthase kinase-3β) was significantly reduced in both the telencephalon and optic tectum of light-altered fish. Animals exposed to five minutes of environmental enrichment showed significant increase in pSer473Akt, which was significantly attenuated by four days of altered light exposure. These data show for the first time that unpredictable light exposure alters HSP70 expression and dysregulates Akt-GSK3β signaling in the adult zebrafish brain.


2021 ◽  
Author(s):  
Gregory M. Su ◽  
Han Wang ◽  
Brandon R. Barnett ◽  
Jeffrey R. Long ◽  
David Prendergast ◽  
...  

In situ near edge X-ray absorption fine structure spectroscopy directly probes unoccupied states associated with backbonding interactions between the open metal site in a metal–organic framework and various small molecule guests.


2021 ◽  
Vol 14 (4) ◽  
pp. 301
Author(s):  
Yayoi Kawano ◽  
Viorica Patrulea ◽  
Emmanuelle Sublet ◽  
Gerrit Borchard ◽  
Takuya Iyoda ◽  
...  

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.


2021 ◽  
Vol 22 (9) ◽  
pp. 4398
Author(s):  
Ana Coelho ◽  
Inês Amaro ◽  
Ana Apolónio ◽  
Anabela Paula ◽  
José Saraiva ◽  
...  

Some authors have been proposing the use of cavity disinfectants in order to reduce, or even eliminate, the effect of the microorganisms present in a dental cavity before a restoration is placed. The aim of this study was to evaluate the effect of different cavity disinfectants on bond strength and clinical success of composite and glass ionomer restorations on primary teeth. The research was conducted using Cochrane Library, PubMed/MEDLINE, SCOPUS, and Web of Science for articles published up to February 2021. The search was performed according to the PICO strategy. The evaluation of the methodological quality of each in vitro study was assessed using the CONSORT checklist for reporting in vitro studies on dental materials. Sixteen in vitro studies and one in situ study fulfilled the inclusion criteria and were analyzed. Chlorhexidine was the most studied cavity disinfectant, and its use does not compromise dentin bonding. Sodium hypochlorite is a promising alternative, but more research on its use is required to clearly state that it can safely be used as a cavity disinfectant for primary teeth. Although other disinfectants were studied, there is a low-level evidence attesting their effects on adhesion, therefore their use should be avoided.


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