Wendy C. Crone

Equilibrium swelling and kinetics of pH-responsive hydrogels: models, experiments, and simulations

The widespread application of ionic hydrogels in a number of applications like control of microfluidic flow, development of muscle-like actuators, filtration/separation and drug delivery makes it important to properly understand these materials. Understanding hydrogel properties is also important from the standpoint of their similarity to many biological tissues. Typically, gel size is sensitive to outer solution pH and salt concentration. In this paper, we develop models to predict the swelling/deswelling of hydrogels in buffered pH solutions. An equilibrium model has been developed to predict the degree of swelling of the hydrogel at a given pH and salt concentration in the solution. A kinetic model has been developed to predict the rate of swelling of the hydrogel when the solution pH is changed. Experiments are performed to characterize the mechanical properties of the hydrogel in different pH solutions. The degree of swelling as well as the rate of swelling of the hydrogel are also studied through experiments. The simulations are compared with experimental results and the models are found to predict the swelling/deswelling processes accurately.

Corrosion and wear-corrosion behavior of NiTi modified by plasma source ion implantation

The understanding of corrosion behavior in NiTi is critical for the devices using this shape-memory alloy. In order to improve the surface properties of NiTi such as corrosion resistance, plasma source ion implantation (PSII) technique was employed with oxygen as incident ions at three levels of implantation dose (5x10(16), 1x10(17) and 3x10(17) ions/cm(-2)). Pitting corrosion and wear-corrosion behavior of control and PSII-modified Ti-50.7at% Ni alloy were evaluated by cyclic potentiodynamic polarization and wear-corrosion measurements. Surface characterization was used to interpret the different corrosion behavior observed between control and oxygen-implanted samples. Results showed that corrosion behavior was influenced by both heat treatment and surface modification. The best pitting corrosion resistance was observed for samples with Af=21 degrees C modified by oxygen implantation at a dose of 1x10(17) ions/cm(-2). Better wear-corrosion resistance was observed for oxygen-implanted samples.

Surface characterization of NiTi modified by plasma source ion implantation

Abstract This paper reports the novel application of an oxygen ion plasma for surface modification of a shape memory alloy. The surface characterization of oxygen ion implanted Ti–50.7 at% Ni alloy samples was performed with the assistance of Auger electron spectroscopy, X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy techniques (TEM). TEM identified amorphous TiO 2 and crystalline phases of Ti 11 Ni 14 and Ti 4 Ni 2 O x . XPS results reveal that the surfaces of control samples are covered with predominantly TiO 2 and traces of TiO and NiTi, as well as NiO and Ni 2 O 3 . At the surface of oxygen-implanted samples, however, only TiO 2 and trace amounts of Ni 2 O 3 , NiO and NiTi were observed. TiO and NiO exist in much larger range than other oxides, and TiO extends to the oxide–metal interface. These results are especially noteworthy because of their implications for interpreting corrosion, wear, and biocompatibility behavior.

3D Collagen Alignment Limits Protrusions to Enhance Breast Cancer Cell Persistence

Patients with mammographically dense breast tissue have a greatly increased risk of developing breast cancer. Dense breast tissue contains more stromal collagen, which contributes to increased matrix stiffness and alters normal cellular responses. Stromal collagen within and surrounding mammary tumors is frequently aligned and reoriented perpendicular to the tumor boundary. We have shown that aligned collagen predicts poor outcome in breast cancer patients, and postulate this is because it facilitates invasion by providing tracks on which cells migrate out of the tumor. However, the mechanisms by which alignment may promote migration are not understood. Here, we investigated the contribution of matrix stiffness and alignment to cell migration speed and persistence. Mechanical measurements of the stiffness of collagen matrices with varying density and alignment were compared with the results of a 3D microchannel alignment assay to quantify cell migration. We further interpreted the experimental results using a computational model of cell migration. We find that collagen alignment confers an increase in stiffness, but does not increase the speed of migrating cells. Instead, alignment enhances the efficiency of migration by increasing directional persistence and restricting protrusions along aligned fibers, resulting in a greater distance traveled. These results suggest that matrix topography, rather than stiffness, is the dominant feature by which an aligned matrix can enhance invasion through 3D collagen matrices.

The effects of prolonged ethanol exposure on the mechanical properties of polyurethane and silicone catheters used for intravascular access.

BACKGROUND Products containing alcohol are commonly used with intravascular devices at insertion, to remove lipids from occluded intravascular devices used during parenteral nutrition, and increasingly for the prevention and treatment of intravascular device-related bloodstream infection. The effects of alcohol on the integrity of intravascular devices remain unknown. METHODS Two types of widely used commercial peripherally inserted central catheters, one made of polyetherurethane and one made of silicone, were exposed to a 70% ethanol lock solution for up to 10 weeks. Mechanical testing was performed to identify force-at-break, stress, strain, modulus of elasticity, modulus of toughness, and wall area of ethanol-exposed and control catheters. RESULTS No significant differences between exposed and unexposed catheters were identified for any of the mechanical parameters tested except for a marginal reduction in the modulus of elasticity for both polyetherurethane and silicone catheters and minor increases in the wall area of polyetherurethane catheters. CONCLUSIONS These data indicate that exposure to a 70% ethanol lock solution does not appreciably alter the integrity of selected commercial polyetherurethane and silicone catheters. Given the greatly expanded use of alcoholic solutions with intravascular devices of all types, we believe that manufacturers would be well advised to subject their catheters and other intravascular devices to formal testing of the type employed in this study.

Effects of substrate mechanics on contractility of cardiomyocytes generated from human pluripotent stem cells.

Human pluripotent stem cell (hPSC-) derived cardiomyocytes have potential applications in drug discovery, toxicity testing, developmental studies, and regenerative medicine. Before these cells can be reliably utilized, characterization of their functionality is required to establish their similarity to native cardiomyocytes. We tracked fluorescent beads embedded in 4.4–99.7 kPa polyacrylamide hydrogels beneath contracting neonatal rat cardiomyocytes and cardiomyocytes generated from hPSCs via growth-factor-induced directed differentiation to measure contractile output in response to changes in substrate mechanics. Contraction stress was determined using traction force microscopy, and morphology was characterized by immunocytochemistry for α-actinin and subsequent image analysis. We found that contraction stress of all types of cardiomyocytes increased with substrate stiffness. This effect was not linked to beating rate or morphology. We demonstrated that hPSC-derived cardiomyocyte contractility responded appropriately to isoprenaline and remained stable in culture over a period of 2 months. This study demonstrates that hPSC-derived cardiomyocytes have appropriate functional responses to substrate stiffness and to a pharmaceutical agent, which motivates their use in further applications such as drug evaluation and cardiac therapies.

Characterization of thermoplastic polyurethane/polylactic acid (TPU/PLA) tissue engineering scaffolds fabricated by microcellular injection molding.

Polylactic acid (PLA) and thermoplastic polyurethane (TPU) are two kinds of biocompatible and biodegradable polymers that can be used in biomedical applications. PLA has rigid mechanical properties while TPU possesses flexible mechanical properties. Blended TPU/PLA tissue engineering scaffolds at different ratios for tunable properties were fabricated via twin screw extrusion and microcellular injection molding techniques for the first time. Multiple test methods were used to characterize these materials. Fourier transform infrared spectroscopy (FTIR) confirmed the existence of the two components in the blends; differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) confirmed the immiscibility between the TPU and PLA. Scanning electron microscopy (SEM) images verified that, at the composition ratios studied, PLA was dispersed as spheres or islands inside the TPU matrix and that this phase morphology further influenced the scaffolds microstructure and surface roughness. The blends exhibited a large range of mechanical properties that covered several human tissue requirements. 3T3 fibroblast cell culture showed that the scaffolds supported cell proliferation and migration properly. Most importantly, this study demonstrated the feasibility of mass producing biocompatible PLA/TPU scaffolds with tunable microstructures, surface roughnesses, and mechanical properties that have the potential to be used as artificial scaffolds in multiple tissue engineering applications.

Shape memory effect in nanoindentation of nickel–titanium thin films

In this study, a series of nanoindentations was made on NiTi shape memory alloy thin films at millinewton loads with a Berkovich indenter. Mapping of the indentation topography using atomic force microscopy reveals direct evidence that the thermally induced martensitic transformation of these films allows for partial indent recovery on the nanoscale. Indeed, recovery is nearly complete at indentation depths of less than 100 nm. A hemispherical cavity model is presented to predict an upper limit to shape memory recovery of sharp indentations.

Measuring the stiffness of bacterial cells from growth rates in hydrogels of tunable elasticity

Although bacterial cells are known to experience large forces from osmotic pressure differences and their local microenvironment, quantitative measurements of the mechanical properties of growing bacterial cells have been limited. We provide an experimental approach and theoretical framework for measuring the mechanical properties of live bacteria. We encapsulated bacteria in agarose with a user‐defined stiffness, measured the growth rate of individual cells and fit data to a thin‐shell mechanical model to extract the effective longitudinal Youngs modulus of the cell envelope of Escherichia coli (50–150 MPa), Bacillus subtilis (100–200 MPa) and Pseudomonas aeruginosa (100–200 MPa). Our data provide estimates of cell wall stiffness similar to values obtained via the more labour‐intensive technique of atomic force microscopy. To address physiological perturbations that produce changes in cellular mechanical properties, we tested the effect of A22‐induced MreB depolymerization on the stiffness of E. coli. The effective longitudinal Youngs modulus was not significantly affected by A22 treatment at short time scales, supporting a model in which the interactions between MreB and the cell wall persist on the same time scale as growth. Our technique therefore enables the rapid determination of how changes in genotype and biochemistry affect the mechanical properties of the bacterial envelope.

Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors

Several studies have reported reprogramming of fibroblasts into induced cardiomyocytes; however, reprogramming into proliferative induced cardiac progenitor cells (iCPCs) remains to be accomplished. Here we report that a combination of 11 or 5 cardiac factors along with canonical Wnt and JAK/STAT signaling reprogrammed adult mouse cardiac, lung, and tail tip fibroblasts into iCPCs. The iCPCs were cardiac mesoderm-restricted progenitors that could be expanded extensively while maintaining multipotency to differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells in vitro. Moreover, iCPCs injected into the cardiac crescent of mouse embryos differentiated into cardiomyocytes. iCPCs transplanted into the post-myocardial infarction mouse heart improved survival and differentiated into cardiomyocytes, smooth muscle cells, and endothelial cells. Lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for drug discovery, disease modeling, and cardiac regenerative therapy.