Adhesion strength and anti-tumor agents regulate vinculin of breast cancer cells.

The onset and progression of cancer are strongly associated with the dissipation of adhesion forces between cancer cells, thus facilitating their incessant attachment and detachment from the extracellular matrix (ECM) to move toward metastasis. During this process, cancer cells undergo mechanical stresses and respond to these stresses with membrane deformation while inducing protrusions to invade the surrounding tissues. Cellular response to mechanical forces is inherently related to the reorganization of the cytoskeleton, the dissipation of cell-cell junctions, and the adhesion to the surrounding ECM. Moreover, the role of focal adhesion proteins, and particularly the role of vinculin in cell attachment and detachment during migration, is critical, indicating the tight cell-ECM junctions, which favor or inhibit the metastatic cascade. The biomechanical analysis of these sequences of events may elucidate the tumor progression and the potential of cancer cells for migration and metastasis. In this work, we focused on the evaluation of the spreading rate and the estimation of the adhesion strength between breast cancer cells and ECM prior to and post-treatment with anti-tumor agents. Specifically, different tamoxifen concentrations were used for ER+ breast cancer cells, while even concentrations of trastuzumab and pertuzumab were used for HER2+ cells. Analysis of cell stiffness indicated an increased elastic Young's modulus post-treatment in both MCF-7 and SKBR-3 cells. The results showed that the post-treatment spreading rate was significantly decreased in both types of breast cancer, suggesting a lower metastatic potential. Additionally, treated cells required greater adhesion forces to detach from the ECM, thus preventing detachment events of cancer cells from the ECM, and therefore, the probability of cell motility, migration, and metastasis was confined. Furthermore, post-detachment and post-treatment vinculin levels were increased, indicating tighter cell-ECM junctions, hence limiting the probability of cell detachment and, therefore, cell motility and migration.

Recent Advancements in 3D Printing and Bioprinting Methods for Cardiovascular Tissue Engineering.

Recent decades have seen a plethora of regenerating new tissues in order to treat a multitude of cardiovascular diseases. Autografts, xenografts and bioengineered extracellular matrices have been employed in this endeavor. However, current limitations of xenografts and exogenous scaffolds to acquire sustainable cell viability, anti-inflammatory and non-cytotoxic effects with anti-thrombogenic properties underline the requirement for alternative bioengineered scaffolds. Herein, we sought to encompass the methods of biofabricated scaffolds via 3D printing and bioprinting, the biomaterials and bioinks recruited to create biomimicked tissues of cardiac valves and vascular networks. Experimental and computational designing approaches have also been included. Moreover, the in vivo applications of the latest studies on the treatment of cardiovascular diseases have been compiled and rigorously discussed.

The Impact of Anti-tumor Agents on ER-Positive MCF-7 and HER2-Positive SKBR-3 Breast Cancer Cells Biomechanics.

Studying human cancer from a biomechanical perspective may contribute to pathogenesis understanding which leads to the malignancy. In this study, biomechanics of suspended and adhered breast cancer cells were investigated via the micropipette aspiration method with special emphasis on comparing the cell stiffness and viscoelastic parameters of estrogen receptor positive, ER+, MCF-7 and human epidermal growth factor receptor 2 positive, HER2 +, SKBR-3 cancer cell lines prior to and post treatment with tamoxifen and trastuzumab, respectively. Alterations of mechanical parameters included significant increase in cell stiffness, especially after treatment with trastuzumab and changes in viscoelastic parameters, in both cancer cell lines post treatment. According to immunofluorescence analysis, the raised cell stiffness was corresponded to remodeling of F-actin, which peripherally located in tamoxifen treated and perinuclear accumulated in trastuzumab treated cancer cell cytoskeleton, implying a reduced potential for cell deformation and motility. Additionally, these results were in line with the study of single and collective cell migration through Boyden chamber and wound healing assays respectively, where the potential for migration was significantly decreased after treatment. Consequently, these findings lead to an increased interest in biomechanics of cancer progression after treatment with anti-tumor agents, importantly in understanding the effect of the alterations of mechanical properties upon the possibility for change in metastatic potential.

Insights into the alteration of osteoblast mechanical properties upon adhesion on chitosan.

Cell adhesion on substrates is accompanied by significant changes in shape and cytoskeleton organization, which affect subsequent cellular and tissue responses, determining the long-term success of an implant. Alterations in osteoblast stiffness upon adhesion on orthopaedic implants with different surface chemical composition and topography are, thus, of central interest in the field of bone implant research. This work aimed to study the mechanical response of osteoblasts upon adhesion on chitosan-coated glass surfaces and to investigate possible correlations with the level of adhesion, spreading, and cytoskeleton reorganization. Using the micropipette aspiration technique, the osteoblast elastic modulus was found higher on chitosan-coated than on uncoated control substrates, and it was found to increase in the course of spreading for both substrates. The cell-surface contact area was measured throughout several time points of adhesion to quantify cell spreading kinetics. Significant differences were found between chitosan and control surfaces regarding the response of cell spreading, while both groups displayed a sigmoidal kinetical behavior with an initially elevated spreading rate which stabilizes in the second hour of attachment. Actin filament structural changes were confirmed after observation with confocal microscope. Biomaterial surface modification can enhance osteoblast mechanical response and induce favorable structural organization for the implant integration.

Attachment, spreading, and adhesion strength of human bone marrow cells on chitosan.

The successful integration of an orthopedic implant into bone depends on the mechanisms at the tissue-implant interface and mostly on the osteoblast attachment phenomenon. Chitosan has emerged as an attractive biomacromolecule favoring osseointegration. In this study highly deacetylated chitosan coatings, with roughness of about 1 nm, were bonded to glass surfaces via silane-glutaraldehyde molecules. Human osteoblasts were used to study the development of attachment during the first 60 min. Chitosan favored the number of the attached cells compared to the uncoated surfaces for 30 min seeding time (t (s)). For t (s) up to 60 min the attached cell area was almost 210% significantly higher on the chitosan surfaces, indicating an enhanced spreading process. To determine the cell attachment strength, a micropipette aspiration method was used, where the value of the term I = ∫Fdt is representative of the single cell attachment-adhesion procedure and quantitatively reflects the strength evolution during attachment: F equals the detaching force applied on the cell. The results showed higher strength values on the chitosan surfaces. The findings reinforce the favorable environment of the biomacromolecule for the osteoblast and the new approach regarding the quantitatively evaluation of adhesion provides important contribution for the study of cell-material interaction, especially during the crucial first phase of cell attachment.

Factors attributed to fatal occupational accidents in a period of 5 years preceding the Athens 2004 Olympic Games.

This study aimed to determine the factors attributed to occupational fatalities occurring in the region of East Attica, Greece, in all industry types over a 5-year period preceding the 2004 Olympic Games. Questionnaires, based on the attribution theory, were completed by labor inspectors and were analyzed with principal component analysis. The results showed that most accidents occurred in the construction industry due to large-scale civil works, which took place in East Attica prior to the 2004 Olympic Games. Poor work practices arising from lack of orientation and job training, performance pressure and workers' inexperience associated with knowledge- and skill-based errors were revealed by the questionnaire as the most common factors attributed to occupational fatalities. Our findings help to identify areas where prevention efforts should be directed to effectively manage safety in Greece.

Red blood cell deformability in patients with sepsis: a marker for prognosis and monitoring of severity.

Sepsis in different states of severity (sepsis, severe sepsis, septic shock and adult respiratory distress syndrome (ARDS)) is associated with microcirculatory blood flow abnormalities leading to decreased red blood cell's (RBC's) deformability, impaired oxygen delivery to tissues and organs failure. The main goal of the present study, was to first determine the values of RBC's deformability, in the course of patients treated in an Intensive Care Unit (ICU) for basically sepsis and then deteriorated states and secondly to establish the prognostic efficiency of the test. For this purpose a filtration method and the hemorheometer, was used to determine experimentally the RBC's deformability, by measuring the RBC's Index of Rigidity (IR). Our results indicated that the IR was significantly increased in all patient groups and it was found to be approximately 51% higher in patients with sepsis, 229% in patients with severe sepsis, 1285% in patients with septic shock and 923% in patients with ARDS than in the healthy donors. The relationships between IR and Simplified Acute Physiology Score II (SAPS) and IR and Projected Mortality (PM) were found to be IR = 2.0237(SAPS) - 58.807 (r=0.731) and IR = 1.0671(PM) - 5.9829 (r=0.726) respectively. Our findings imply a significant impairment of the membrane's deformability possibly due to changes in its structure. It seems that the RBC's deformability is a useful mechanical parameter to estimate the prognosis and monitor patients suffering from different severity levels of sepsis.