Bioinspired ultra-low fouling coatings on medical devices to prevent device-associated infections and thrombosis.

Addressing thrombosis and biofouling of indwelling medical devices within healthcare institutions is an ongoing problem. In this work, two types of ultra-low fouling surfaces (i.e.

Fabrication of Bacteria- and Blood-Repellent Superhydrophobic Polyurethane Sponge Materials.

Biofilm and thrombus formation on surfaces results in significant morbidity and mortality worldwide, which highlights the importance of the development of efficacious fouling-prevention approaches. In this work, novel highly robust and superhydrophobic coatings with outstanding multiliquid repellency, bactericidal performance, and extremely low bacterial and blood adhesion are fabricated by a simple two-step dip-coating method. The coatings are prepared combining 1,1,2,2-perfluorooctyltriethoxysilane (FAS-17)-coated hydrophobic zinc oxide and copper nanoparticles to construct hierarchical micro/nanostructures on commercial polyurethane (PU) sponges followed by polydimethylsiloxane (PDMS) treatment that is used to improve the binding degree between the nanoparticles and the sponge surface.

Author Correction: Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity.

Direct recognition of invading pathogens by innate immune cells is a critical driver of the inflammatory response. However, cells of the innate immune system can also sense their local microenvironment and respond to physiological fluctuations in temperature, pH, oxygen and nutrient availability, which are altered during inflammation. Although cells of the immune system experience force and pressure throughout their life cycle, little is known about how these mechanical processes regulate the immune response.

Left Ventricular Hemodynamics with an Implanted Assist Device: An In Vitro Fluid Dynamics Study.

Left ventricle assist devices (VADs) aid the heart pumping blood into the systemic circulation and grant the required cardiac output (CO) when the heart itself cannot provide it. However, it is unclear how effective these devices are at restoring not only physiological CO values but also normal intraventricular hemodynamics. In this work, the modified hemodynamics due to a VAD implantation is studied in vitro using an elastic ventricle made of silicone, which is incorporated into a pulse-duplicator setup prescribing a realistic pulsatile flow.

Quantitative Characterization of Aortic Valve Endothelial Cell Viability and Morphology In Situ Under Cyclic Stretch.

Current protocols for mechanical preconditioning of tissue engineered heart valves have focused on application of pressure, flexure and fluid flow to stimulate collagen production, ECM remodeling and improving mechanical performance. The aim of this study was to determine if mechanical preconditioning with cyclic stretch could promote an intact endothelium that resembled the viability and morphology of a native valve. Confocal laser scanning microscopy was used to image endothelial cells on aortic valve strips subjected to static incubation or physiological strain regimens.

Side-specific characterization of aortic valve endothelial cell adhesion molecules under cyclic strain.

Background And Aim Of The Study: Aortic valve ectopic calcification occurs exclusively on the fibrosa surface. This may be due to the distinct mechanical environments on either side of the valve, or to the existence of unique, side-specific endothelial sub-phenotypes. The study aim was to determine if side-specific endothelial cells (ECs) would differentially express cell-cell and cell-matrix adhesion molecules in response to elevated levels of equibiaxial tensile strain.

Cyclic pressure and angiotensin II influence the biomechanical properties of aortic valves.

Hypertension is a known risk factor for aortic stenosis. The elevated blood pressure increases the transvalvular load and can elicit inflammation and extracellular matrix (ECM) remodeling. Elevated cyclic pressure and the vasoactive agent angiotensin II (Ang II) both promote collagen synthesis, an early hallmark of aortic sclerosis.

Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks.

The study aimed to identify mechanosensitive pathways and gene networks that are stimulated by elevated cyclic pressure in aortic valve interstitial cells (VICs) and lead to detrimental tissue remodeling and/or pathogenesis. Porcine aortic valve leaflets were exposed to cyclic pressures of 80 or 120 mmHg, corresponding to diastolic transvalvular pressure in normal and hypertensive conditions, respectively. Linear, two-cycle amplification of total RNA, followed by microarray was performed for transcriptome analysis (with qRT-PCR validation).

Design of a cyclic pressure bioreactor for the ex vivo study of aortic heart valves.

The aortic valve, located between the left ventricle and the aorta, allows for unidirectional blood flow, preventing backflow into the ventricle. Aortic valve leaflets are composed of interstitial cells suspended within an extracellular matrix (ECM) and are lined with an endothelial cell monolayer. The valve withstands a harsh, dynamic environment and is constantly exposed to shear, flexion, tension, and compression.

Live en face imaging of aortic valve leaflets under mechanical stress.

Soft tissues, such as tendons, skin, arteries, or lung, are constantly subject to mechanical stresses in vivo. None more so than the aortic heart valve that experiences an array of forces including shear stress, cyclic pressure, strain, and flexion. Anisotropic biaxial cyclic stretch maintains valve homeostasis; however, abnormal forces are implicated in disease progression.

Introduction to viral vectors.

Viral vector is the most effective means of gene transfer to modify specific cell type or tissue and can be manipulated to express therapeutic genes. Several virus types are currently being investigated for use to deliver genes to cells to provide either transient or permanent transgene expression. These include adenoviruses (Ads), retroviruses (γ-retroviruses and lentiviruses), poxviruses, adeno-associated viruses, baculoviruses, and herpes simplex viruses.

Vasoactive agents alter the biomechanical properties of aortic heart valve leaflets in a time-dependent manner.

Background And Aim Of The Study: Although the vasoactive agents, angiotensin II (Ang II) and 5-hydroxytryptamine (5-HT) are implicated in aortic heart valve disease, it is unclear how these compounds alter the biomechanical properties of valve leaflet tissue. The study aim was to characterize temporal changes in the elastic modulus of tissues incubated with these compounds.

Methods: Valve leaflets were excised from fresh porcine aortic heart valves.

Cyclic strain inhibits acute pro-inflammatory gene expression in aortic valve interstitial cells.

Mechanical in vitro preconditioning of tissue engineered heart valves is viewed as an essential process for tissue development prior to in vivo implantation. However, a number of pro-inflammatory genes are mechanosensitive and their elaboration could elicit an adverse response in the host. We hypothesized that the application of normal physiological levels of strain to isolated valve interstitial cells would inhibit the expression of pro-inflammatory genes.

Cell culture processes for the production of viral vectors for gene therapy purposes.

Gene therapy is a promising technology for the treatment of several acquired and inherited diseases. However, for gene therapy to be a commercial and clinical success, scalable cell culture processes must be in place to produce the required amount of viral vectors to meet market demand. Each type of vector has its own distinct characteristics and consequently its own challenges for production.

Cyclic strain regulates pro-inflammatory protein expression in porcine aortic valve endothelial cells.

Background And Aim Of The Study: The endothelium of diseased heart valves is known to express the adhesion molecules VCAM-1, ICAM-1 and E-selectin, while healthy valves lack these pro-inflammatory proteins. The study aim was to determine if mechanical forces were responsible for the pro-inflammatory reaction in aortic valve endothelial cells.

Methods: Isolated porcine aortic valve endothelial cells (PAVEC) were cultured and seeded onto BioFlexTM culture plates.

Influence of hydrostatic and distortional stress on chondroinduction.

Undifferentiated connective tissue that arises during embryonic development and some healing processes contains pluripotent mesenchymal stem cells. It is becoming increasingly evident that the mechanical environment is an important differentiation factor for these cells. In our laboratory, we have focused on the potential for mechanical signals to induce chondrogenic differentiation of mesenchymal stem cells.

Mechanobiology of the aortic heart valve.

The aortic heart valve is a complex and sophisticated structure that functions in a mechanically challenging environment. With each cardiac cycle, blood flow exerts shear stresses, bending stress and tensile and compressive forces on the valve tissue. These forces determine a plethora of biological responses, including gene expression, protein activation and cell phenotype.

Evaluation of porcine aortic valve interstitial cell activity using different serum types in two- and three-dimensional culture.

Unlike established cell lines used in the biotechnology industry, primary cells used in tissue engineering require culture media to be supplemented with serum. The most common serum is fetal bovine serum (FBS); however, FBS is expensive, negatively affecting process economics. Less-costly alternative sera are commercially available, but their efficacy has not been documented.

Bioreactor systems for the production of biopharmaceuticals from animal cells.

The demand for biopharmaceutical products is set to see a significant increase over the next few years. As a consequence, the processes used to produce these products must be able to meet market requirements. The present paper reviews the current technologies available for animal cell culture and highlights the advantages and disadvantages of each method, while also providing details of recent case studies.

Cyclic aortic pressure affects the biological properties of porcine pulmonary valve leaflets.

Background And Aim Of The Study: Native pulmonary valve leaflets (PVL) are exposed to lower pressures compared to aortic valve leaflets. Knowledge of the biology of PVL exposed to aortic pressures is limited. Hence, the study's aim was to investigate the biological properties of PVL subjected to normal aortic pressures.

Flow and thrombosis at orifices simulating mechanical heart valve leakage regions.

Background: While it is established that mechanical heart valves (MHVs) damage blood elements during leakage and forward flow, the role in thrombus formation of platelet activation by high shear flow geometries remains unclear. In this study, continuously recalcified blood was used to measure the effects of blood flow through orifices, which model MHVs, on the generation of procoagulant thrombin and the resulting formation of thrombus. The contribution of platelets to this process was also assessed.

Differential immediate-early gene responses to elevated pressure in porcine aortic valve interstitial cells.

Background And Aim Of The Study: Cardiovascular risk factors are believed to play a role in the pathogenesis of aortic valve disease. In the present study the hypothesis was proposed that elevated pressure would cause a change in the expression of prototypical pro-inflammatory genes. Hence, the expression of MCP-1, osteopontin (OPN), VCAM-1, GM-CSF and PAI-1 was examined using semi-quantitative real-time RT-PCR.

Design of a sterile organ culture system for the ex vivo study of aortic heart valves.

The biological response of valves to mechanical forces is not well understood. The aim of this study was to design a pulsatile system to enable the ex vivo study of aortic valves when subjected to various hemodynamic conditions. A bioreactor was designed to subject porcine aortic valves to physiological and pathophysiological pressure and flow conditions, while maintaining viability and sterility.

Normal physiological conditions maintain the biological characteristics of porcine aortic heart valves: an ex vivo organ culture study.

The aortic valve functions in a complex mechanical environment which leads to force-dependent cellular and tissue responses. Characterization of these responses provides a fundamental understanding of valve pathogenesis. The aim of this work was to study the biological characteristics of native porcine aortic valves cultured in an ex vivo pulsatile organ culture system capable of maintaining physiological pressures (120/80 mmHg) and cardiac output (4.