Animals are commonly used for pharmacokinetic studies which are the most frequent events tested during ocular drug development and preclinical evaluation. Inaccuracy, cost, and ethical criticism in these tests have created a need to construct an in vitro model for studying corneal constraints. In this work, a porous membrane embedded microfluidic platform is fabricated that separates a chip into an apical and basal side. After functionalizing the membrane surface with fibronectin, the membrane's mechanical and surface properties are measured to ensure correct modeling of in vivo characteristics. Immortalized human corneal epithelial cells are cultured on the membrane to create a microengineered corneal epithelium-on-a-chip (cornea chip) that is validated with experiments designed to test the barrier properties of the human corneal epithelium construct using model drugs. A pulsatile flow model is used that closely mimics the ocular precorneal constraints and is reasonable for permeability analysis that models in vivo conditions. This model can be used for preclinical evaluations of potential therapeutic drugs and to mimic the environment of the human cornea.
This research focuses on the design of biocompatible materials/scaffold suitable for use for tissue engineering. Porous fiber mats were produced through electrospinning of polythiophene phenylene (PThP) conducting polymers blended with poly(lactide- co-glycolic acid) (PLGA). A peptide containing an arginylglycylaspartic acid (RGD) fragment was synthesized using solid phase peptide synthesis and subsequently grafted onto a PThP polymer using azide-alkyne "click" chemistry. The obtained RGD functionalized PThP was also electrospun into a fiber mat. The electrospun mats' morphology, roughness and stiffness were studied by means of scanning electron microscopy (SEM) and atomic force microscopy (AFM) and their electroactivity by cyclic voltammetry. The fibers show excellent cytocompatibility in culture assays with human dermal fibroblasts-adult (HDFa) and human epidermal melanocytes-adult (HEMa) cells. The electrospun fibers' roughness and stiffness changed after exposing the fiber mats to the cell culture medium (measured in dry state), but these changes did not affect the cell proliferation. The cytocompatibility of our porous scaffolds was established for their applicability as cell culture scaffolds by means of investigating mitochondrial activity of HDFa and HEMa cells on the scaffolds. The results revealed that the RGD moieties containing PThP scaffolds hold a promise in biomedical applications, including skin tissue engineering.
1. Electrolyte imbalance is a common complication in cancer that mainly involves sodium, potassium, and calcium alterations. 2. If the individual at risk is not monitored and hydrated, it leads to severe complications.3. Hydration status assessed in various indices; plasma, sweat, saliva, urine, interstitial fluid, and skin interface have been widely used, but no unified (de)hydration monitoring technologies exist for different populations.
This Article describes an unprecedented, simple, and real-time in vitro analytical tool to measure the luminous effect on the time responses function of retinal ganglion cells (RGC-5) by electric cell substrate impedance sensing (ECIS) system. The ECIS system was used for the continuous measurement of different color light-induced effects on the response of cells that exposed to protective drugs. The measurement suggests that the association of photo-oxidative stress was mediated by reactive oxygen species (ROS), which plays a critical role that leads to cell stress, damages, and retinopathy, resulting in eye degenerative diseases. Continuous light radiation caused time-dependent decline of RGC-5 response and resulted in photodamage within 10 h due to adenosine 5'-triphosphate depletion and increased ROS level, which is similar to in vivo photodamage. The ECIS results were correlated with standard cell viability assay. ECIS is very helpful to determine the protective effects of analyzed drugs such as β-carotene, quercetin, agmatine, and glutathione in RGC-5 cells, and the maximum drug activity of nontoxic safer drug concentrations was found to be 0.25, 0.25, 0.25, and 1.0 mM, respectively. All drugs show protection against light radiation toxicity in a dose-dependent manner; the most effective drug was found to be glutathione. The proposed system identifies the phototoxic effects in RGC-5 and provides high throughput drug screening for photo-oxidative stress during early stages of drug discovery. This study is convenient and potential enough for the direct measurements of the photoprotective effect in vitro and would be of broad interest in the field of therapeutics.
Glucosamine (GlcN), an amino-monosaccharide, is known to be a safe and efficient drug for the treatment of various inflammatory diseases, including osteoarthritis and rheumatoid arthritis. In this current study, the main issues of high hydrophilicity and poor permeability of GlcN for its use as a transdermal delivery system were overcome by conjugation with the hydrophobic polymer poly(D,L-lactic-co-glycolic acid) (PLGA) and its self-assembly into nanostructures containing nanoparticles (NPs). The self-assembly of the PLGA-GlcN nanostructure was facilitated by probe sonication, which was based on the cavitation and nucleation concept, followed by reversible locking. Hydrophobic PLGA assembly onto the outer surface and hydrophilic GlcN into the inner core helps the nanostructure more flexibly permeate through the skin lipid membrane and release GlcN in a sustained manner for 48 h. Ex vivo transdermal permeation of PLGA-GlcN nanostructures through human cadaver skin exhibited a better permeation profile, which demonstrated the shortest lag time with a higher flux value than the other formulations, such as the GlcN solution, GlcN NPs and PLGA-GlcN solution.
The aim of this study was to analyze photo-dynamic and photo-pathology changes of different color light radiations on human adult skin cells. We used a real-time biophysical and biomechanics monitoring system for light-induced cellular changes in an in vitro model to find mechanisms of the initial and continuous degenerative process. Cells were exposed to intermittent, mild and intense (1-180 min) light with On/Off cycles, using blue, green, red and white light. Cellular ultra-structural changes, damages, and ECM impair function were evaluated by up/down-regulation of biophysical, biomechanical and biochemical properties. All cells exposed to different color light radiation showed significant changes in a time-dependent manner. Particularly, cell growth, stiffness, roughness, cytoskeletal integrity and ECM proteins of the human dermal fibroblasts-adult (HDF-a) cells showed highest alteration, followed by human epidermal keratinocytes-adult (HEK-a) cells and human epidermal melanocytes-adult (HEM-a) cells. Such changes might impede the normal cellular functions. Overall, the obtained results identify a new insight that may contribute to premature aging, and causes it to look aged in younger people. Moreover, these results advance our understanding of the different color light-induced degenerative process and help the development of new therapeutic strategies.
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