Effect of cell imprinting on viability and drug susceptibility of breast cancer cells to doxorubicin.

This study demonstrates the effect of substrate's geometrical cues on viability and the efficacy of an anti-cancer drug, doxorubicin (DOX), on breast cancer cells. It is hypothesized that the surface topographical properties can mediate the cellular drug intake. Pseudo-three dimensional (3D) platforms were fabricated using imprinting technique from polydimethylsiloxane (PDMS) and gelatin methacryloyl (GelMA) hydrogel to recapitulate topography of cells' membranes. The cells exhibited higher viability on the cell-imprinted platforms for both PDMS and GelMA materials compared to the plain/flat counterparts. For instance, MCF7 cells showed a higher metabolic activity (11.9%) on MCF7-imprinted PDMS substrate than plain PDMS. The increased metabolic activity for the imprinted GelMA was about 44.2% compared to plain hydrogel. The DOX response of cells was monitored for 24 h. Although imprinted substrates demonstrated enhanced biocompatibility, the cultured cells were more susceptible to the drug compared to the plain substrates. In particular, MCF7 cells on imprinted PDMS and GelMA substrates showed 37% and 50% higher in cell death compared to the corresponding plain PDMS and GelMA, respectively. Interestingly, the drug susceptibility of the cells on the imprinted hydrogel was about 70% higher than the cells cultured on imprinted PDMS substrates. Having MCF7 cell-imprinted substrates, DOX responses of two other breast cancer cell lines, SKBR3 and ZR-75-1, were also evaluated. The results support that cell membrane curvature developed by multiscale topography is able to mediate intracellular signaling and drug intake. STATEMENT OF SIGNIFICANCE: Research in biological sciences and drug discovery mostly rely on two dimensional (2D) cell culture techniques which cannot provide a reliable physiologically relevant environment. Lack of extracellular matrix and a large shift in physicochemical properties of conventional 2D substrates can induce aberrant cellular behaviors. While chemical composition, topographical, and mechanical properties of substrates have remarkable impacts on drug susceptibility, gene expression, and protein synthesis, the most cell culture plates are from rigid and plain substrates. A number of (bio)polymeric 3D-platforms have been introduced to resemble innate cell microenvironment. However, their intricate culture protocols restrain their applications in demanding high-throughput drug screening. To address the above concerns, in the present study, a hydrogel-based pseudo-3D substrate with imprinted cell features has been introduced.

The Correlation of Microstructure and Mechanical Properties of In-Situ Al-Mg2Si Cast Composite Processed by Equal Channel Angular Pressing.

In this paper, the effect of equal channel angular pressing (ECAP) on microstructure and mechanical properties of hypereutectic Al-20%Mg2Si and Al-15%Mg2Si, as well as hypoeutectic Al-10%Mg2Si composites has been investigated. After fabricating the composites by in-situ casting, the composites were processed using the ECAP process up to two passes at room temperature. Microstructural studies have been carried out using a field emission scanning electron microscopy equipped with an energy dispersive X-ray spectrometer. Mechanical properties were also documented using Vickers microhardness and shear punch tests. In the hypereutectic composites, a decrease in the average size of pro-eutectic Mg2Si (Mg2Sip) particles, breakages in eutectic networks, and lengthening of the Al (α) phase in direction of shear bands were observed after the ECAP process. For instance, the average size of Mg2Sip Particles in Al-20%Mg2Si composite reduced from 40 to 17 µm after 2 passes of ECAP. Furthermore, a uniform distribution of Mg2Sip particles was developed in the matrix. In hypoeutectic composite, the ECAP process caused a uniform distribution of eutectic Mg2Si (Mg2SiE) in the matrix that considered a favorable microstructure. Microhardness measurements and shear punch results showed an ascending trend after each pass of ECAP for all specimens. For example, microhardness and shear strength of Al-20%Mg2Si increased from 88 HV and 109 MPa to 119 HV and 249 MPa after two passes indicating 35% and 34% increments, respectively. Density and porosity calculations by Archimedes principle revealed that the density of the composites increased after two passes of ECAP due to the reduction of porosity.

Microstructure, Texture, Electrical and Mechanical Properties of AA-6063 Processed by Multi Directional Forging.

In current research, the effect of the multi-directional forging (MDF) process on the microstructure, texture, mechanical and electrical properties of AA-6063 under different heat treatment conditions at various MDF temperatures was studied. The annealed AA-6063 alloy was processed up to three passes of MDF at ambient temperature. Three passes of this process were also applied to the solution-treated AA-6063 at ambient temperature and 177 °C. Microstructural investigations demonstrated that the MDF process led to a significant reduction in the average grain size as well as a considerable increase in the fraction of low angle grain boundaries. Texture analysis revealed that copper and Goss textures were mainly developed within the annealed and solution-treated samples of AA-6063, respectively. The hardness and shear strength values of all processed samples also showed a sizeable improvement compared to the initial heat-treated samples. For example, the hardness and shear yield strength value of the solution-treated sample MDFed for three passes showed more than 100 and 70% increase, respectively. The effect of the MDF process on the electrical conductivity of AA-6063 under different heat treatment conditions at various temperatures was negligible. So, it can be concluded that the MDF process increased the mechanical properties without an appreciable decrease in electrical conductivity.