An engineered in vitro model of the human myotendinous junction.

The myotendinous junction (MTJ) is a vulnerable region at the interface of skeletal muscle and tendon that forms an integrated mechanical unit. This study presents a technique for the spatially restrictive co-culture of human embryonic stem cell (hESC)-derived skeletal myocytes and primary tenocytes for two-dimensional modeling of the MTJ. Micropatterned lanes of extracellular matrix and a 2-well culture chamber define the initial regions of occupation. On day 1, both lines occupy less than 20 % of the initially vacant interstitial zone, referred to henceforth as the junction. Myocyte-tenocyte interdigitations are observed by day 7. Immunocytochemistry reveals enhanced organization and alignment of patterned myocyte and tenocyte features, as well as differential expression of multiple MTJ markers. On day 24, electrically stimulated junction myocytes demonstrate negative contractile strains, while positive tensile strains are exhibited by mechanically passive tenocytes at the junction. Unpatterned tenocytes distal to the junction experience significantly decreased strains in comparison to cells at the interface. Unpatterned myocytes have impaired organization and uncoordinated contractile behavior. These findings suggest that this platform is capable of inducing myocyte-tenocyte junction formation and mechanical coupling similar to the native MTJ, showing transduction of force across the cell-cell interface. STATEMENT OF SIGNIFICANCE: The myotendinous junction (MTJ) is an integrated structure that transduces force across the muscle-tendon boundary, making the region vulnerable to strain injury. Despite the clinical relevance, previous in vitro models of the MTJ lack the structure and mechanical accuracy of the native tissue and have difficulty transmitting force across the cell-cell interface. This study demonstrates an in vitro model of the MTJ, using spatially restrictive cues to inform human myocyte-tenocyte interactions and architecture. The model expressed MTJ markers and developed anisotropic myocyte-tenocyte integrations that resemble the native tissue and allow for force transduction from contracting myocytes to passive tenocyte regions. As such, this study presents a system capable of investigating development, injury, and pathology in the human MTJ.

Cultivating well-being in engineering graduate students through mindfulness training.

The mental health crisis in graduate education combined with low treatment rates among engineering graduate students underscores the need for engineering graduate programs to provide effective methods to promote well-being. There is an extensive body of neuroscience research showing that contemplative practices, such as mindfulness, produce measurable effects on brain function and overall well-being. We hypothesized that a mindfulness-based training program designed for engineering graduate students would improve emotional well-being and, secondarily, enhance research capacity. An initial pilot study was conducted at a single institution (Phase 1), followed by a larger study conducted at both the original and a second institution (Phase 2) to gather additional data and show the program's transferability. The program comprised eight weekly mindfulness training sessions. Individuals in the study were randomly assigned to either an intervention group or wait-list control group. We administered pre- and post-test surveys with quantitative measures designed to assess emotional and physical well-being, as well as creativity, research satisfaction, and desire to contribute to the betterment of society. Participants also completed a summative survey to evaluate the impact of the program on their well-being and research. Analysis revealed statistically significant findings: improved emotional health, decreased neuroticism, increased positive affect, decreased negative affect, and increased mindfulness in the intervention groups compared to the control groups. Intervention groups in Phase 2 also reported statistically significant improvement in satisfaction with their research. Our findings suggest that mindfulness training has the potential to play a vital professional and personal development role in graduate engineering education.

cMyBP-C ablation in human engineered cardiac tissue causes progressive Ca2+-handling abnormalities.

Truncation mutations in cardiac myosin binding protein C (cMyBP-C) are common causes of hypertrophic cardiomyopathy (HCM). Heterozygous carriers present with classical HCM, while homozygous carriers present with early onset HCM that rapidly progress to heart failure. We used CRISPR-Cas9 to introduce heterozygous (cMyBP-C+/-) and homozygous (cMyBP-C-/-) frame-shift mutations into MYBPC3 in human iPSCs. Cardiomyocytes derived from these isogenic lines were used to generate cardiac micropatterns and engineered cardiac tissue constructs (ECTs) that were characterized for contractile function, Ca2+-handling, and Ca2+-sensitivity. While heterozygous frame shifts did not alter cMyBP-C protein levels in 2-D cardiomyocytes, cMyBP-C+/- ECTs were haploinsufficient. cMyBP-C-/- cardiac micropatterns produced increased strain with normal Ca2+-handling. After 2 wk of culture in ECT, contractile function was similar between the three genotypes; however, Ca2+-release was slower in the setting of reduced or absent cMyBP-C. At 6 wk in ECT culture, the Ca2+-handling abnormalities became more pronounced in both cMyBP-C+/- and cMyBP-C-/- ECTs, and force production became severely depressed in cMyBP-C-/- ECTs. RNA-seq analysis revealed enrichment of differentially expressed hypertrophic, sarcomeric, Ca2+-handling, and metabolic genes in cMyBP-C+/- and cMyBP-C-/- ECTs. Our data suggest a progressive phenotype caused by cMyBP-C haploinsufficiency and ablation that initially is hypercontractile, but progresses to hypocontractility with impaired relaxation. The severity of the phenotype correlates with the amount of cMyBP-C present, with more severe earlier phenotypes observed in cMyBP-C-/- than cMyBP-C+/- ECTs. We propose that while the primary effect of cMyBP-C haploinsufficiency or ablation may relate to myosin crossbridge orientation, the observed contractile phenotype is Ca2+-mediated.

Challenges and innovation: Disease modeling using human-induced pluripotent stem cell-derived cardiomyocytes.

Disease modeling using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has both challenges and promise. While patient-derived iPSC-CMs provide a unique opportunity for disease modeling with isogenic cells, the challenge is that these cells still demonstrate distinct properties which make it functionally less akin to adult cardiomyocytes. In response to this challenge, numerous innovations in differentiation and modification of hiPSC-CMs and culture techniques have been developed. Here, we provide a focused commentary on hiPSC-CMs for use in disease modeling, the progress made in generating electrically and metabolically mature hiPSC-CMs and enabling investigative platforms. The solutions are bringing us closer to the promise of modeling heart disease using human cells in vitro.

Wavy small-diameter vascular graft made of eggshell membrane and thermoplastic polyurethane.

In this study, a small-diameter, double-layered eggshell membrane/thermoplastic polyurethane (ESM/TPU) vascular graft with a wavy structure was developed. The avian eggshell membrane, a fibrous structure similar to the extracellular matrix (ECM), has the potential to yield rapid endothelialization in vitro. The dopamine and heparin modification of the ESM surface not only promoted human umbilical vein endothelial cell (HUVEC) proliferation via cytocompatibility assessment, but also improved its anticoagulation properties as verified in platelet adhesion tests. The biomimetic mechanical properties of the vascular graft were provided by the elastic TPU fibers via electrospinning using a wavy cross-section rotating collector. The advantage of combining these two materials is to make use of the bioactivity of ESM as the internal membrane and the tunable mechanical properties of TPU as the external layer. The circumferentially wavy structure of the vascular graft produced a toe region in the non-linear section of the stress-strain curve similar to that of natural blood vessels. The ESM/TPU graft's circumferential ultimate strength was 2.57 MPa, its strain was 339% mm/mm, and its toe region was found to be around 20% mm/mm. Cyclical tension tests showed that the vascular graft could maintain good mechanical properties and showed no structural damage under repeated extension tests.

Micropatterned substrates with physiological stiffness promote cell maturation and Pompe disease phenotype in human induced pluripotent stem cell-derived skeletal myocytes.

Recent advances in bioengineering have enabled cell culture systems that more closely mimic the native cellular environment. Here, we demonstrated that human induced pluripotent stem cell (iPSC)-derived myogenic progenitors formed highly-aligned myotubes and contracted when seeded on two-dimensional micropatterned platforms. The differentiated cells showed clear nuclear alignment and formed elongated myotubes dependent on the width of the micropatterned lanes. Topographical cues from micropatterning and physiological substrate stiffness improved the formation of well-aligned and multinucleated myotubes similar to myofibers. These aligned myotubes exhibited spontaneous contractions specifically along the long axis of the pattern. Notably, the micropatterned platforms developed bundle-like myotubes using patient-derived iPSCs with a background of Pompe disease (glycogen storage disease type II) and even enhanced the disease phenotype as shown through the specific pathology of abnormal lysosome accumulations. A highly-aligned formation of matured myotubes holds great potential in further understanding the process of human muscle development, as well as advancing in vitro pharmacological studies for skeletal muscle diseases.

Epigenetic Priming of Human Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Accelerates Cardiomyocyte Maturation.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) exhibit a fetal phenotype that limits in vitro and therapeutic applications. Strategies to promote cardiomyocyte maturation have focused interventions on differentiated hPSC-CMs, but this study tests priming of early cardiac progenitor cells (CPCs) with polyinosinic-polycytidylic acid (pIC) to accelerate cardiomyocyte maturation. CPCs were differentiated from hPSCs using a monolayer differentiation protocol with defined small molecule Wnt temporal modulation, and pIC was added during the formation of early CPCs. pIC priming did not alter the expression of cell surface markers for CPCs (>80% KDR+/PDGFRα+), expression of common cardiac transcription factors, or final purity of differentiated hPSC-CMs (∼90%). However, CPC differentiation in basal medium revealed that pIC priming resulted in hPSC-CMs with enhanced maturity manifested by increased cell size, greater contractility, faster electrical upstrokes, increased oxidative metabolism, and more mature sarcomeric structure and composition. To investigate the mechanisms of CPC priming, RNAseq revealed that cardiac progenitor-stage pIC modulated early Notch signaling and cardiomyogenic transcriptional programs. Chromatin immunoprecipitation of CPCs showed that pIC treatment increased deposition of the H3K9ac activating epigenetic mark at core promoters of cardiac myofilament genes and the Notch ligand, JAG1. Inhibition of Notch signaling blocked the effects of pIC on differentiation and cardiomyocyte maturation. Furthermore, primed CPCs showed more robust formation of hPSC-CMs grafts when transplanted to the NSGW mouse kidney capsule. Overall, epigenetic modulation of CPCs with pIC accelerates cardiomyocyte maturation enabling basic research applications and potential therapeutic uses. Stem Cells 2019;37:910-923.

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.

Substrate stiffness effect and chromosome missegregation in hIPS cells.

BACKGROUND: Ensuring genetic stability in pluripotent stem cell (PSC) cultures is essential for the development of successful cell therapies. Although most instances lead to failed experiments and go unreported in the literature, many laboratories have found the emergence of genetic abnormalities in PSCs when cultured in vitro for prolonged amounts of time. These cells are primarily cultured in non-physiological stiff substrates like tissue culture polystyrene (TCPS) which raises the possibility that the cause of these abnormalities may be influenced by substrate mechanics. FINDINGS: In order to investigate this, human PSCs were grown on substrates of varying stiffness such as a range of polyacrylamide formulations, TCPS, and borosilicate glass coverslips. These substrates allowed for the testing of a stiffness range from 5kPa to 64GPa. Two human induced PSC (iPSC) lines were analyzed in this study: 19-9-11 iPSCs and 19.7 clone F iPSCs. Centrosome and DNA staining revealed that 19-9-11 iPSCs range from 1-8.5 % abnormal mitoses under the different culture conditions. A range of 4.4-8.1 % abnormal mitoses was found for 19.7 clone F iPSCs. CONCLUSIONS: Abnormal cell division was not biased towards one particular substrate. It was confirmed by Analysis of Variance (ANOVA) and Tukey's Honest Significant Difference test that there was no statistically significant difference between passage numbers, cell lines, or substrates.

Stretch calculated from grip distance accurately approximates mid-specimen stretch in large elastic arteries in uniaxial tensile tests.

The mechanical properties of vascular tissues affect hemodynamics and can alter disease progression. The uniaxial tensile test is a simple and effective method for determining the stress-strain relationship in arterial tissue ex vivo. To enable calculation of strain, stretch can be measured directly with image tracking of markers on the tissue or indirectly from the distance between the grips used to hold the specimen. While the imaging technique is generally considered more accurate, it also requires more analysis, and the grip distance method is more widely used. The purpose of this study is to compare the stretch of the testing specimen calculated from the grip distance method to that obtained from the imaging method for canine descending aortas and large proximal pulmonary arteries. Our results showed a significant difference in stretch between the two methods; however, this difference was consistently less than 2%. Therefore, the grip distance method is an accurate approximation of the stretch in large elastic arteries in the uniaxial tensile test.

Preliminary in vivo evaluation of a novel intrasaccular cerebral aneurysm occlusion device.

OBJECTIVE: Current endovascular technology does not offer a perfect solution for all cerebral aneurysms. Our group has built two versions of a novel aneurysm intrasaccular occlusion device (AIOD) to address the drawbacks associated with current occlusion devices. The objective of the present study was to perform pilot proof of concept in vivo testing of this new AIOD in swine and canines. METHODS: Two configurations of the AIOD, termed 'coil-in-shell' and 'gel-in-shell', were implanted in surgically created sidewall aneurysms (n=4) in swine for acute occlusion studies, as well as sidewall (n=8) and bifurcation aneurysms (n=3) in canines to assess long term occlusion efficacy. Occlusion at all time points (immediate, 6 weeks, and 12 weeks) was evaluated by angiography. Neointimal healing at 12 weeks post-implantation in canines was examined histologically. RESULTS: Angiographic analysis showed that both the coil-in-shell and gel-in-shell devices achieved complete aneurysm occlusion immediately following device delivery in sidewall aneurysms in swine. In longer term canine studies, initial occlusion ranged from 71.3% to 100%, which was stable with no recurrence in any of the sidewall aneurysms at 6 or 12 weeks. Histological analysis at 12 weeks showed mature fibromuscular tissue at the neck of all aneurysms and no significant inflammatory response. CONCLUSIONS: The AIOD tested in this study showed promise in terms of acute and chronic occlusion of aneurysms. Our findings suggest that these devices have the potential to promote robust tissue healing at the aneurysm neck, which may minimize aneurysm recurrence. Although proof of principle has been shown, further work is needed to deliver this device through an endovascular route.

Electrospinning of unidirectionally and orthogonally aligned thermoplastic polyurethane nanofibers: fiber orientation and cell migration.

Unidirectionally and orthogonally aligned thermoplastic polyurethane (TPU) nanofibers were electrospun using a custom-built electrospinning device. The unidirectionally aligned fibers were collected using two parallel copper plates, and the orthogonally aligned fibers were collected using two orthogonal sets of parallel copper plates with alternate negative connections. Carbon nanotubes (CNT) and polyacrylic acid (PAA) were added to modify the polymer solution. It was found that both CNT and PAA were capable of increasing solution conductivity. The TPU/PAA fiber showed the highest degree of fiber orientation with more than 90% of the fibers having an orientation angle between -10° and 10° for unidirectionally aligned fibers, and for orthogonally aligned fibers, the orientation angle of 50% fibers located between -10° and 10° and 48% fibers located between 80° and 100°. Viability assessment of 3T3 fibroblasts cultured on TPU/PAA fibers suggested that the material was cytocompatible. The cells' orientation and migration direction closely matched the fibers' orientation. The cell migration velocity and distance were both enhanced with the guidance of fibers compared with cells cultured on random fibers and common tissue culture plastic. Controlling cell migration velocity and directionality may provide ways to influence differentiation and gene expression and systems that would allow further exploration of wound repair and metastatic cell 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.

Micropattern width dependent sarcomere development in human ESC-derived cardiomyocytes.

In this study, human embryonic stem cell-derived cardiomyocytes were seeded onto controlled two-dimensional micropatterned features, and an improvement in sarcomere formation and cell alignment was observed in specific feature geometries. High-resolution photolithography techniques and microcontact printing were utilized to produce features of various rectangular geometries, with areas ranging from 2500 µm(2) to 160,000 µm(2). The microcontact printing method was used to pattern non-adherent poly(ethylene glycol) regions on gold coated glass slides. Matrigel and fibronectin extracellular matrix (ECM) proteins were layered onto the gold-coated glass slides, providing a controlled geometry for cell adhesion. We used small molecule-based differentiation and an antibiotic purification step to produce a pure population of immature cardiomyocytes from H9 human embryonic stem cells (hESCs). We then seeded this pure population of human cardiomyocytes onto the micropatterned features of various sizes and observed how the cardiomyocytes remodeled their myofilament structure in response to the feature geometries. Immunofluorescence was used to measure α-actinin expression, and phalloidin stains were used to detect actin presence in the patterned cells. Analysis of nuclear alignment was also used to determine how cell direction was influenced by the features. The seeded cells showed clear alignment with the features, dependent on the width rather than the overall aspect ratio of the features. It was determined that features with widths between 30 µm and 80 µm promoted highly aligned cardiomyocytes with a dramatic increase in sarcomere alignment relative to the long axis of the pattern. This creation of highly-aligned cell aggregates with robust sarcomere structures holds great potential in advancing cell-based pharmacological studies, and will help researchers to understand the means by which ECM geometries can affect myofilament structure and maturation in hESC-derived cardiomyocytes.

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 scaffold's 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.

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.

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 Young's 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 Young's 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.

Polyurethane/dermatan sulfate copolymers as hemocompatible, non-biofouling materials.

The range of application of polyurethanes has been limited by their poor hemocompatibility and inability to resist non-specific binding of biomolecules and cells. In this work, a non-adhesive PU-based material was synthesized via the copolymerization of PU with dermatan sulfate. Incorporation of DS into the PU backbone dramatically increased material hydrophilicity and decreased protein adsorption. The in vitro adhesion of several cell types, including platelets, also significantly decreased with increasing DS content. Both the physical and biological properties of the DS contributed to the anti-adhesive properties of the PU/DS copolymer, and this anti-adhesive nature of PU/DS renders this new biomaterial attractive for blood-contacting or non-fouling applications.

The haemocompatibility of polyurethane-hyaluronic acid copolymers.

Despite decades of research into haemocompatible biomaterials, there remain surprisingly few materials that can be used in blood-contacting applications. We have synthesized copolymers of polyurethane (PU) with hyaluronic acid (HA) with the goal of creating materials that incorporate an inherently non-thrombogenic, biological component into the bulk polymer structure. HA was incorporated into the polymer backbone as a chain extender during PU synthesis, and the physical and biological properties of the resulting copolymer were directly controlled by the HA content. Increases in HA content led to a linear increase in hydrophilicity (R(2)=0.993) and corresponding increase in surface energy compared to PU controls. Elastic modulus also increased with HA content (p<0.001), while surface roughness did not significantly differ from PU controls for most PU-HA formulations. Incorporation of HA resulted in negligible platelet adhesion to the PU-HA (p<0.001), representing a 20-fold decrease in platelet adhesion compared to PU. Red blood cell adhesion also decreased with increasing HA content (p<0.001). The PU-HA materials were cytocompatible and supported endothelial cell adhesion and viability. Thus, we have demonstrated the synthesis of a copolymer whose physical and biological properties are easily tailored, and whose potent anti-thrombogenic properties demonstrate its great promise for use in vascular applications.

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.