Rheological Assessment for Determining Form Stability of Wound Dressings.

The classification of wound care products as form-stable dressings remains challenging due to the lack of objective and quantitative, material-science-based criteria. This study introduces a rheological testing framework to determine form stability of wound dressing materials. Using dynamic, oscillatory shear rheology, we evaluated the viscoelastic properties and responses of two tube-dispensed model dressings and compared them to those of honey, a high-viscosity liquid used in wound ointments.

Mechanobiological cell adaptations to changing microenvironments determine cancer invasiveness: Experimentally validated finite element modeling.

Metastases are the leading cause of cancer-associated deaths. A key process in metastasis is cell invasiveness, which is driven and controlled by cancer cell interactions with their microenvironment. We have previously shown that invasive cancer cells forcefully push into and indent physiological stiffness gels to cell-scale depths, where the percentage of indenting cells and their attained depths provide clinically relevant predictions of tumor invasiveness and the potential metastatic risk.

Physical confinement and cell proximity increase cell migration rates and invasiveness: A mathematical model of cancer cell invasion through flexible channels.

Cancer cell migration between different body parts is the driving force behind cancer metastasis, which is the main cause of mortality of patients. Migration of cancer cells often proceeds by penetration through narrow cavities in locally stiff, yet flexible tissues. In our previous work, we developed a model for cell geometry evolution during invasion, which we extend here to investigate whether leader and follower (cancer) cells that only interact mechanically can benefit from sequential transmigration through narrow micro-channels and cavities.

Computational modeling reveals a vital role for proximity-driven additive and synergistic cell-cell interactions in increasing cancer invasiveness.

Solid-tumor cell invasion typically occurs by collective migration of attached cell-cohorts, yet we show here that indirect cell-interactions through the substrate can also drive invasiveness. We have previously shown that well-spaced, invasive cancer cells push-into and indent gels to depths of 10 µm, while closely adjacent, non-contacting cancer cells may reach up to 18 µm, potentially relying on cell-cell interactions through the gel-substrate. To test that, we developed finite element models of indenting cells, using experimental gel mechanics, cell mechanostructure, and force magnitudes.

Breast cancer stem cells: mechanobiology reveals highly invasive cancer cell subpopulations.

Cancer stem-like cells (CSCs) are a typically small subpopulation of highly tumorigenic cells that can self-renew, differentiate, drive tumor progression, and may mediate drug resistance and metastasis. Metastasis driving CSCs are expected to be highly invasive. To determine the relative invasiveness of CSCs, we isolate distinct subpopulations in the metastatic, MDA-MB-231 breast-cancer cell line, identified by the stem-cell markers aldehyde dehydrogenase (ALDH) and CD44.

T Cells Promote Metastasis by Regulating Extracellular Matrix Remodeling following Chemotherapy.

Metastasis is the main cause of cancer-related mortality. Despite intense efforts to understand the mechanisms underlying the metastatic process, treatment of metastatic cancer is still challenging. Here we describe a chemotherapy-induced, host-mediated mechanism that promotes remodeling of the extracellular matrix (ECM), ultimately facilitating cancer cell seeding and metastasis.

Mechanical interactions of invasive cancer cells through their substrate evolve from additive to synergistic.

Non-contacting, adjacent cancer cells can mechanically interact through their substrate to increase their invasive and migratory capacities that underly metastases-formation. Such mechanical interactions may induce additive or synergistic enhancement of invasiveness, potentially indicating different underlying force-mechanisms. To identify cell-cell-gel interactions, we monitor the time-evolution of three-dimensional traction strains induced by MDA-MB-231 breast cancer cells adhering on physiological-stiffness (1.

Rapid, quantitative prediction of tumor invasiveness in non-melanoma skin cancers using mechanobiology-based assay.

Non-melanoma skin cancers, including basal and squamous cell carcinomas (BCC and SCC), are the most common malignancies worldwide. BCC/SCC cancers are generally highly localized and can be surgically excised; however, invasive tumors may be fatal. Current diagnosis of skin cancer and prognosis of potential invasiveness are based mainly on clinical-pathological factors of the biopsied lesions.

Modeling force application configurations and morphologies required for cancer cell invasion.

We show that cell-applied, normal mechanical stresses are required for cells to penetrate into soft substrates, matching experimental observations in invasive cancer cells, while in-plane traction forces alone reproduce observations in non-cancer/noninvasive cells. Mechanobiological interactions of cells with their microenvironment drive migration and cancer invasion. We have previously shown that invasive cancer cells forcefully and rapidly push into impenetrable, physiological stiffness gels and indent them to cell-scale depths (up to 10 μm); normal, noninvasive cells indent at most to 0.

Machine-Learning Provides Patient-Specific Prediction of Metastatic Risk Based on Innovative, Mechanobiology Assay.

Cancer mortality is mostly related to metastasis. Metastasis is currently prognosed via histopathology, disease-statistics, or genetics; those are potentially inaccurate, not rapidly available and require known markers. We had developed a rapid (~ 2 h) mechanobiology-based approach to provide early prognosis of the clinical likelihood for metastasis.

Actin as a Target to Reduce Cell Invasiveness in Initial Stages of Metastasis.

We demonstrate the relative roles of the cell cytoskeleton, and specific importance of actin in facilitating mechanical aspects of metastatic invasion. A crucial step in metastasis, the typically lethal spread of cancer to distant body-sites, is cell invasion through dense tissues composed of extracellular matrix and various non-cancerous cells. Cell invasion requires cell-cytoskeleton remodeling to facilitate dynamic morphological changes and force application.

Two- and three-dimensional de-drifting algorithms for fiducially marked image stacks.

Traction force microscopy has been established as the accepted method for evaluating cell-induced mechanical stresses to their microenvironments, typically using two-dimensional (2D) elastic, synthetic gel-substrates. As cells naturally experience 3D environments in vivo, traction microscopy has been adapted to 3D gels; cells can be tracked over time in 3D. Microscopy images acquired in several fields-of-view e.

Lung mechanics modifications facilitating metastasis are mediated in part by breast cancer-derived extracellular vesicles.

Tumor microenvironment-mechanics greatly affect tumor-cell characteristics such as invasion and proliferation. We and others have previously shown that after chemotherapy, tumor cells shed more extracellular vesicles (EVs), leading to tumor growth and even spread, via angiogenesis and the mobilization of specific bone-marrow-derived cells contributing to metastasis. However, physical, mechanobiological and mechanostructural changes at premetastatic sites that may support tumor cell seeding, have yet to be determined.

Finite element analysis reveals an important role for cell morphology in response to mechanical compression.

Mechanical loading naturally controls cell phenotype, development, motility and various other biological functions; however, prolonged or substantial loading can cause cell damage and eventual death. Loading-induced mechanobiological and mechanostructural responses of different cell types affect their morphology and the internal architecture and the mechanics of the cellular components. Using single, mesenchymal stem cells, we have developed a cell-specific three-dimensional finite-element model; cell models were developed from phase-contrast microscopy images.

Micropatterned topographies reveal measurable differences between cancer and benign cells.

During metastasis, cancer cells migrate away from the primary tumor-site, encountering different microenvironment topographies that may facilitate or inhibit cancer cell adherence and growth; those relate to sites of invasion and seeding. To evaluate topography effects, poly-lactic-poly-glycolic (PLGA) gels are generated as flat substrates, porous, or with rectangular microchannels of varying widths (5-100 µm) and depths (10/20 µm). The topography effect on time-dependent adherence, proliferation, morphology, alignment and long-term structural development of metastatic breast-cancer and benign cells are evaluated; adherence at short time-scales (3 h) is compared to developed morphologies and multicellular structures (>2 days) indicating function.

Computational modeling of therapy on pancreatic cancer in its early stages.

More than eighty percent of pancreatic cancer involves ductal adenocarcinoma with an abundant desmoplastic extracellular matrix surrounding the solid tumor entity. This aberrant tumor microenvironment facilitates a strong resistance of pancreatic cancer to medication. Although various therapeutic strategies have been reported to be effective in mice with pancreatic cancer, they still need to be tested quantitatively in wider animal-based experiments before being applied as therapies.

Sodium pyruvate pre-treatment prevents cell death due to localised, damaging mechanical strains in the context of pressure ulcers.

We demonstrate sodium pyruvate (NaPy) pre-treatment as a successful approach for pressure ulcer (PU) prevention by averting their aetiological origin-cell-level damage and death by large, sustained mechanical loads. We evaluated the NaPy pre-treatment effect on permeability changes in the cell's plasma membrane (PM) following application of in vitro damaging-level strains. Fibroblasts or myoblasts, respectively, models for superficial or deep-tissue damage were grown in 0 or 1 mM NaPy, emulating typical physiological or cell culture conditions.

Non-damaging stretching combined with sodium pyruvate supplement accelerate migration of fibroblasts and myoblasts during gap closure.

Background: Sustained, low- and mid-level (3-6%), radial stretching combined with varying concentrations of sodium pyruvate (NaPy) supplement increase the migration rate during microscale gap closure following an in vitro injury; NaPy is a physiological supplement often used in cell-culture media. Recently we showed that low-level tensile strains accelerate in vitro kinematics during en masse cell migration; topically applied mechanical deformations also accelerate in vivo healing in larger wounds. The constituents and nutrients at injury sites change.

A phenomenological model for cell and nucleus deformation during cancer metastasis.

Cell migration plays an essential role in cancer metastasis. In cancer invasion through confined spaces, cells must undergo extensive deformation, which is a capability related to their metastatic potentials. Here, we simulate the deformation of the cell and nucleus during invasion through a dense, physiological microenvironment by developing a phenomenological computational model.

Control of cell proliferation by a porous chitosan scaffold with multiple releasing capabilities.

The aim of this study was to develop a porous chitosan scaffold with long-acting drug release as an artificial dressing to promote skin wound healing. The dressing was fabricated by pre-freezing at different temperatures (-20 and -80 °C) for different periods of time, followed by freeze-drying to form porous chitosan scaffolds with different pore sizes. The chitosan scaffolds were then used to investigate the effect of the controlled release of fibroblast growth factor-basic (bFGF) and transforming growth factor-β1 (TGFβ1) on mouse fibroblast cells (L929) and bovine carotid endothelial cells (BEC).

A model for cell migration in non-isotropic fibrin networks with an application to pancreatic tumor islets.

Cell migration, known as an orchestrated movement of cells, is crucially important for wound healing, tumor growth, immune response as well as other biomedical processes. This paper presents a cell-based model to describe cell migration in non-isotropic fibrin networks around pancreatic tumor islets. This migration is determined by the mechanical strain energy density as well as cytokines-driven chemotaxis.

Complex, Dynamic Behavior of Extremely Asymmetric Di-n-Alkylphosphate-Anion Aggregates, the Long-Chain Effect and the Role of a Limiting Size: Cryo-TEM, SANS, and X-Ray Diffraction Studies.

For extremely asymmetric n-hexyl(n-decyl)phosphate (HDeP), n-hexyl(n-dodecyl)phosphate (HDoP), and n-hexyl(n-cetyl)phosphate (HCeP), the effect of the long-chains on the dynamic behavior of their aggregate structures in water was examined by cryo-TEM imaging, SANS, and X-ray diffraction techniques. The cryo-TEM images demonstrated the complex and dynamic behavior of the aggregates, and its dependence on the length of the long-chain. Application of the one-dimensional aggregate theory to the SANS results led to the conclusion that the existence of a limiting size also depended on the length of the main long-hydrocarbon chain and affected strongly the dynamic behavior of the aggregates, causing breakage of thread-like micelles or ribbon-like aggregates.

Proximity of Metastatic Cells Enhances Their Mechanobiological Invasiveness.

A critical step in metastases formation is cancer-cell invasion through tissue. During invasion, cells change morphology and apply forces to their surroundings. We have previously shown that single, metastatic breast-cancer cells will mechanically indent a synthetic, impenetrable polyacrylamide gel with physiological-stiffness in attempted invasion; benign breast cells do not indent the gels.