Cytotoxic Effect of Betulinic Acid on Vascular Smooth Muscle Cells

Betulinic Acid (BA) is a widely available plant-derived triterpene reported as a selective cytotoxic activity against cancer cell of neuroectodermal origin and leukaemias. Interestingly, this will be first report to demonstrate the cytotoxic effect of BA in VSMCs. First, MTT cytotoxic assay was used to measure cell viability of VSMCs with predetermined concentrations of BA for 24h, 48h and 72h. The results obtain indicated that BA inhibit the growth and proliferation of VSMCs in a dose dependent manner IC10 of 0.4μg/ml, IC25 of 1μg/ml and IC50 of 3.8 μg/ml significantly (P<0.05). Secondly, the genotoxic potential associated to exposure to BA was assessed on VSMCs in vitro by the comet assay. BA exhibits low level of DNA damage and not likely to increase the level of DNA damage after 24 h exposure. Moreover, Flow cytometric analysis revealed that BA treatment FOR 24 h induced cell cycle arrest at the G1 phase and caused the appearance of a sub-G1 DNA peak at 48 h. Finally, the cell death morphology indicates that the percentage of apoptotic at 24 h were 12.43 ± 1.55% and at 48 h were 23.17 ± 1.73%, the percentage of necrotic cells at 48 h were 14.63 ± 1.45%. An increase percentage of apoptotic cells at 72 h were 45.92 ± 1.45%. In conclusion, exposure of BA to VSMCs initiate early DNA damage, arrest at G1 phase and induce apoptosis

Betulinic Acid Inhibits Growth of Cultured Vascular Smooth Muscle Cells In Vitro

Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC) is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC50 of 3.8 μg/mL significantly (P<0.05). Nevertheless, betulinic acid exhibited G1 cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24 h of treatment. In conclusion, betulinic acid induced G1 cell cycle arrest and dose-dependent DNA damage on VSMC

A Versatile Sacrificial Layer for Transfer Printing of Wide Bandgap Materials for Implantable and Stretchable Bioelectronics

Improving and optimizing the processes for transfer printing have the potential to further enhance capabilities in heterogeneous integration of various sensing materials on unconventional substrates for implantable and stretchable electronic devices in biosensing, diagnostics, and therapeutic applications. An advanced transfer printing method based on sacrificial layer engineering for silicon carbide materials in stretchable electronic devices is presented here. In contrast to the typical processes where defined anchor structures are required for the transfer step, the use of a sacrificial layer offers enhances versatility in releasing complex microstructures from rigid donor substrates to flexible receiver platforms. The sacrificial layer also minimizes twisting and wrinkling issues that may occur in free- standing microstructures, thereby facilitating printing onto flat polymer surfaces (e.g., polydimethylsiloxane). The experimental results demonstrate that transferred SiC microstructures exhibit good stretchability, stable electrical properties, excellent biocompatibility, as well as promising sensing- functions associated with a high level of structural perfection, without any cracks or tears. This transfer printing method can be applied to other classes of wide bandgap semiconductors, particularly group III- nitrides and diamond films epitaxially grown on Si substrates, thereby serving as the foundation for the development and possible commercialization of implantable and stretchable bioelectronic devices that exploit wide bandgap materials.Employing a dissolvable film as a supporting layer for the fabrication of free- standing silicon carbide microstructures, the present work eliminates the wrinkling and twisting phenomena associated with nanomembranes grown at high temperatures. This technique enables transfer- printing of diverse microstructures of wide band gap semiconductors onto a soft substrate, creating a new class of stretchable electronics for biosensing and implanting applications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163418/3/adfm202004655_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163418/2/adfm202004655.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163418/1/adfm202004655-sup-0001-SuppMat.pd

Integrating Oxygen and 3D Cell Culture System: A Simple Tool to Elucidate the Cell Fate Decision of hiPSCs

Oxygen, as an external environmental factor, plays a role in the early differentiation of human stem cells, such as induced pluripotent stem cells (hiPSCs). However, the effect of oxygen concentration on the early-stage differentiation of hiPSC is not fully understood, especially in 3D aggregate cultures. In this study, we cultivated the 3D aggregation of hiPSCs on oxygen-permeable microwells under different oxygen concentrations ranging from 2.5 to 20% and found that the aggregates became larger, corresponding to the increase in oxygen level. In a low oxygen environment, the glycolytic pathway was more profound, and the differentiation markers of the three germ layers were upregulated, suggesting that the oxygen concentration can function as a regulator of differentiation during the early stage of development. In conclusion, culturing stem cells on oxygen-permeable microwells may serve as a platform to investigate the effect of oxygen concentration on diverse cell fate decisions during development

Stretchable Bioelectronics: A Versatile Sacrificial Layer for Transfer Printing of Wide Bandgap Materials for Implantable and Stretchable Bioelectronics (Adv. Funct. Mater. 43/2020)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163481/1/adfm202070287.pd

Transparent crystalline cubic SiC-on-glass electrodes enable simultaneous electrochemistry and optical microscopy

This work presents crystalline SiC-on-glass as a transparent, robust, and optically stable electrode for simultaneous electrochemical characterization and optical microscope imaging. Experimental results show a large potential window, as well as excellent stability and repeatability over multiple cyclic voltammetric scans in common redox biomarkers such as ruthenium hexaammine and methylene blue. The high optical transmittance and biocompatibility of SiC-on-glass were also observed, enabling cell culture, electrical stimulation, and high resolution fluorescence imaging. This new platform opens exciting opportunities in multi-functional biosensing-probes and observation

Long-lived, transferred crystalline silicon carbide nanomembranes for implantable flexible electronics

Implantable electronics are of great interest owing to their capability for real-time and continuous recording of cellular-electrical activity. Nevertheless, as such systems involve direct interfaces with surrounding biofluidic environments, maintaining their long-term sustainable operation, without leakage currents or corrosion, is a daunting challenge. Herein, we present a thin, flexible semiconducting material system that offers attractive attributes in this context. The material consists of crystalline cubic silicon carbide nanomembranes grown on silicon wafers, released and then physically transferred to a final device substrate (e.g., polyimide). The experimental results demonstrate that SiC nanomembranes with thicknesses of 230 nm do not experience the hydrolysis process (i.e., the etching rate is 0 nm/day at 96 degrees C in phosphate-buffered saline (PBS)). There is no observable water permeability for at least 60 days in PBS at 96 degrees C and non-Na+ ion diffusion detected at a thickness of 50 nm after being soaked in 1 x PBS for 12 days. These properties enable Faradaic interfaces between active electronics and biological tissues, as well as multimodal sensing of temperature, strain, and other properties without the need for additional encapsulating layers. These findings create important opportunities for use of flexible, wide band gap materials as essential components of long-lived neurological and cardiac electrophysiological device interfaces