In this article, pH-responsive near-infrared emitting conjugated polymer nanoparticles (CPNs) are prepared, characterized, and their stabilities are investigated under various conditions. These nanoparticles have capacity to be loaded with water insoluble, anticancer drug, camptothecin (CPT), with around 10% drug loading efficiency. The in vitro release studies demonstrate that the release of CPTs from CPNs is pHdependent such that significantly faster drug release at mildly acidic pH of 5.0 compared with physiological pH 7.4 is observed. Time and dose-dependent in vitro cytotoxicity tests of blank and CPT-loaded nanoparticles are performed by realtime cell electronic sensing (RT-CES) assay with hepatocellular carcinoma cells (Huh7). The results indicate that CPNs can be effectively utilized as vehicles for pH-triggered release of anticancer drugs.
Magnetic fields with different frequency and intensity parameters exhibit a wide range of effects on different biological models. Extremely low frequency magnetic field (ELF MF) exposure is known to augment or even initiate neuronal differentiation in several in vitro and in vivo models. This effect holds potential for clinical translation into treatment of neurodegenerative conditions such as autism, Parkinson's disease and dementia by promoting neurogenesis, non-invasively. However, the lack of information on underlying mechanisms hinders further investigation into this phenomenon. Here, we examine involvement of glutamatergic Ca 2+ channel, N-methyl-d-aspartate (NMDA) receptors in the process of human neuronal differentiation under ELF MF exposure. We show that human neural progenitor cells (hNPCs) differentiate more efficiently under ELF MF exposure in vitro, as demonstrated by the abundance of neuronal markers. Furthermore, they exhibit higher intracellular Ca 2+ levels as evidenced by c-fos expression and more elongated mature neurites. We were able to neutralize these effects by blocking NMDA receptors with memantine. As a result, we hypothesize that the effects of ELF MF exposure on neuronal differentiation originate from the effects on NMDA receptors, which sequentially triggers Ca 2+-dependent cascades that lead to differentiation. Our findings identify NMDA receptors as a new key player in this field that will aid further research in the pursuit of effect mechanisms of ELF MFs. Keywords Extremely low frequency magnetic field (ELF MF) • Neuronal differentiation • N-methyl-d-aspartate (NMDA) receptor • Human neural progenitor cells (hNPCs) Abbreviations ADAM10 A disintegrin and metalloproteinase AMPA Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid CREB Cyclic AMP-responsive element-binding protein DAPI 4-6-diamidino-2-phenylindole-dihydrochloride EGFR Epidermal growth factor receptor ELF MF Extremely low frequency magnetic field hNPCs Human neural progenitor cells mT MilliTesla NMDA N-methyl-d-aspartate
Corneal endothelial cells (CECs) have limited proliferation ability leading to corneal endothelium (CE) dysfunction and eventually vision loss when cell number decreases below a critical level. Although transplantation is the main treatment method, donor shortage problem is a major bottleneck. The transplantation of in vitro developed endothelial cells with desirable density is a promising idea. Designing cell substrates that mimic the native CE microenvironment is a substantial step to achieve this goal. In the presented study, we prepared polyacrylamide (PA) cell substrates that have a microfabricated topography inspired by the dimensions of CECs. Hydrogel surfaces were prepared via two different designs with small and large patterns. Small patterned hydrogels have physiologically relevant hexagon densities (∼2000 hexagons/mm2), whereas large patterned hydrogels have sparsely populated hexagons (∼400 hexagons/mm2). These substrates have similar elastic modulus of native Descemet's membrane (DM; ∼50 kPa) and were modified with Collagen IV (Col IV) to have biochemical content similar to native DM. The behavior of bovine corneal endothelial cells on these substrates was investigated and results show that cell proliferation on small patterned substrates was significantly (p = 0.0004) higher than the large patterned substrates. Small patterned substrates enabled a more densely populated cell monolayer compared to other groups (p = 0.001 vs. flat and p < 0.0001 vs. large patterned substrates). These results suggest that generating bioinspired surface topographies augments the formation of CE monolayers with the desired cell density, addressing the in vitro development of CE layers.
This review provides a comprehensive compendium of commonly used biomaterials as well as the different fabrication techniques employed for the design of 3D neural tissue models.
Electrospinning (ES) of gelatin often requires cytotoxic organic solvents or acidic environments, which deteriorate cell recognition sites. In this study, aqueous, non-toxic, co-solvent ES was performed to obtain core-shell poly(vinyl alcohol) (PVA)/gelatin nanofiber scaffolds. Effects of the core/shell feed rate ratio (FRR) were investigated on a morphological and mechanical basis. PVA:gelatin ratio of 1:4 was the limiting ratio for specific voltage and electrode distance parameters to obtain uniform fibers. Core-shell bead-free structures were obtained at 8% PVA and gelatin aqueous solutions. A mean diameter of 280 nm was obtained for 1:1 FRR at 15 kV and 15 cm of electrode distance. Crosslinking resulted in slight improvement in tensile strengths and severe decrease in ductility. Fourier transform infrared spectra revealed retention and improvement of stable secondary structures of gelatin after ES. The scaffolds almost degraded more than 60% in 14 days. Based on the results, present scaffolds hold great promise as suitable candidates for biomedical applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.