Joanna Stasiak

Evaluation of an aortic valve prosthesis: Fluid-structure interaction or structural simulation?

Bio-inspired polymeric heart valves (PHVs) are excellent candidates to mimic the structural and the fluid dynamic features of the native valve. PHVs can be implanted as prosthetic alternative to currently clinically used mechanical and biological valves or as potential candidate for a minimally invasive treatment, like the transcatheter aortic valve implantation. Nevertheless, PHVs are not currently used for clinical applications due to their lack of reliability. In order to investigate the main features of this new class of prostheses, pulsatile tests in an in-house pulse duplicator were carried out and reproduced in silico with both structural Finite-Element (FE) and Fluid-Structure interaction (FSI) analyses. Valve kinematics and geometric orifice area (GOA) were evaluated to compare the in vitro and the in silico tests. Numerical results showed better similarity with experiments for the FSI than for the FE simulations. The maximum difference between experimental and FSI GOA at maximum opening time was only 5%, as compared to the 46.5% between experimental and structural FE GOA. The stress distribution on the valve leaflets clearly reflected the difference in valve kinematics. Higher stress values were found in the FSI simulations with respect to those obtained in the FE simulation. This study demonstrates that FSI simulations are more appropriate than FE simulations to describe the actual behaviour of PHVs as they can replicate the valve-fluid interaction while providing realistic fluid dynamic results.

Hybrid membrane biomaterials from self-assembly in polysaccharide and peptide amphiphile mixtures: controllable structural and mechanical properties and antimicrobial activity

Macroscopic capsules, with tunable properties based on hierarchical self-assembly on multiple lengthscales, are prepared from the co-operative self-assembly of polysaccharide and peptide amphiphiles. Different formulations can be used to create flexible membrane sacs in solution, soft capsules or rigid free-standing capsules. Samples are prepared by injecting a solution containing sodium alginate, with or without graphene oxide (GO), into a matrix consisting of a solution containing the peptide amphiphile PA C16-KKFF (K: lysine, F: phenylalanine), with or without CaCl2. Graphene oxide is added to the hybrid materials to modulate the mechanical properties of the capsules. Injection of sodium alginate solution into a pure PA matrix provides a flexible membrane sac in solution, while injection of NaAlg/GO solution into a PA matrix gives a soft capsule. Alternatively, a rigid free-standing capsule is made by injecting a NaAlg/GO solution into a PA + CaCl2 matrix solution. A comprehensive insight into the hierarchical order within the capsules is provided through analysis of X-ray scattering data. A novel “Langmuir–Blodgett” mechanism is proposed to account for the formation of the sacs and capsules as the alginate solution is injected at the interface of the PA solution. The capsules show a unique antibacterial effect specific for the Gram positive bacterium Listeria monocytogenes, which is an important human pathogen. The hybrid nanostructured capsules thus have remarkable bioactivity and due to their tunable structural and functional properties are likely to have a diversity of other future applications.

Mechanical strength of sutured block copolymers films for load bearing medical applications.

The mechanical behavior of three styrenic thermoplastic block copolymer elastomers with applied surgical sutures was studied by uniaxial tensile testing. The materials exhibited oriented cylindrical microstructure. Distinct macroscopic deformation mechanisms have been observed upon stretching of samples with vertical and horizontal orientation. Deformation progressed along the axis of the suture in samples with parallel orientation (P), while it in case of normal orientation (N) the whole sample responded to the applied force. Also the analysis of the stress-strain curves showed a significant difference between samples P and N. Greater stress at break was observed for samples P, while samples N showed the capability to tolerate higher strain. The influence of morphology on the tear-out shape has been also observed. The thread made a vertical tear out in samples P while for samples N ripping off the bottom was observed.

ENGINEERING ORIENTATION IN BLOCK COPOLYMERS FOR APPLICATION TO PROSTHETIC HEART VALVES

This study demonstrates how the mechanical performance of polymeric material can be enhanced by morphology and phase orientation of block copolymers to achieve desired anisotropic mechanical properties. The material used was a new Kraton block copolymer consisting of styrene-isoprene-butadiene-styrene blocks having cylindrical morphology. We report a method of achieving long range uniaxial as well as biaxial orientation of block copolymer. Each microstructural organization results in a specific mechanical performance, which depends on the direction of the applied deformation. The method of tailoring mechanical properties by engineering microstructure may be successfully utilized to applications requiring anisotropic mechanical response, such as prosthetic heart valves.

Hemocompatibility of styrenic block copolymers for use in prosthetic heart valves

Certain styrenic thermoplastic block copolymer elastomers can be processed to exhibit anisotropic mechanical properties which may be desirable for imitating biological tissues. The ex-vivo hemocompatibility of four triblock (hard–soft–hard) copolymers with polystyrene hard blocks and polyethylene, polypropylene, polyisoprene, polybutadiene or polyisobutylene soft blocks are tested using the modified Chandler loop method using fresh human blood and direct contact cell proliferation of fibroblasts upon the materials. The hemocompatibility and durability performance of a heparin coating is also evaluated. Measures of platelet and coagulation cascade activation indicate that the test materials are superior to polyester but inferior to expanded polytetrafluoroethylene and bovine pericardium reference materials. Against inflammatory measures the test materials are superior to polyester and bovine pericardium. The addition of a heparin coating results in reduced protein adsorption and ex-vivo hemocompatibility performance superior to all reference materials, in all measures. The tested styrenic thermoplastic block copolymers demonstrate adequate performance for blood contacting applications.

A NEWLY DEVELOPED TRI-LEAFLET POLYMERIC HEART VALVE PROSTHESIS

The potential of polymeric heart valves (PHV) prostheses is to combine the hemodynamic performances of biological valves with the durability of mechanical valves. The aim of this work is to design and develop a new tri-leaflet prosthetic heart valve (HV) made from styrenic block copolymers. A computational finite element model was implemented to optimize the thickness of the leaflets, to improve PHV mechanical and hydrodynamic performances. Based on the model outcomes, 8 prototypes of the designed valve were produced and tested in vitro under continuous and pulsatile flow conditions, as prescribed by ISO 5840 Standard. A specially designed pulse duplicator allowed testing the PHVs at different flow rates and frequency conditions. All the PHVs met the requirements specified in ISO 5840 Standard in terms of both regurgitation and effective orifice area (EOA), demonstrating their potential as HV prostheses.

A real time SAXS study of oriented block copolymers during fast cyclical deformation, with potential application for prosthetic heart valves

Simultaneous small angle X-ray scattering (SAXS) and force measurements have been recorded during tensile loading/unloading deformation cycles of three oriented thermoplastic elastomers. SAXS patterns were obtained in only 10 ms, during deformation. Over this timescale, the microstructure of the materials reacted instantly to the applied deformation. Microstructural changes were followed over 10 000 cycles, each cycle period being less than 1 s. Morphological evolution from the initial state as the deformation proceeded has been linked to mechanical properties. The direction of orientation was the most significant parameter determining the mechanical strength of tested materials, followed by styrene weight fraction. Samples oriented parallel to the deformation direction showed greater resistance to applied force and also better microstructural reversibility over the 10 000 cycles.

A SAXS study of flow alignment of thermotropic liquid crystal mixtures

We report on the capillary flow behaviour of thermotropic liquid crystal mixtures containing 4-n-octyl-4′-cyanobiphenyl (8CB) and 4-n-pentyl-4′-cyanobiphenyl (5CB). The liquid crystal mixtures are studied in the Nematic (N) and Smectic (SA) phases at room temperature. Polarised optical microscopy (POM), rheology and simultaneous X-ray diffraction (XRD)/capillary flow experiments are performed to characterise the system. Polarised optical microscopy reveals a dramatic change in optical texture when the 5CB content is increased from 20 to 30% in the mixtures. X-ray diffraction results show that the system goes through a SA–N phase transition, such that the mixtures are smectic for 10–20% 5CB and nematic for 30–90% 5CB. Smectic mixtures flow with the layers aligned along the flow direction (mesogens perpendicular to flow) while nematic mixtures flow with the mesogens aligned in the flow direction. Simultaneous XRD/shear flow experiments show that the SA–N transition is independent of the flow rate in the range 1–6 ml min−1. The correlation length of the liquid crystal order decreases with increasing 5CB content. Rheology is used to prove that the correlation length behaviour is related to a reduction in the viscosity of the mixture.

Shear Alignment of Bola-Amphiphilic Arginine-Coated Peptide Nanotubes

The bola-amphiphilic arginine-capped peptide RFL4RF self-assembles into nanotubes in aqueous solution. The nanostructure and rheology are probed by in situ simultaneous rheology/small-angle scattering experiments including rheo-SAXS, rheo-SANS, and rheo-GISANS (SAXS: small-angle X-ray scattering, SANS: small-angle neutron scattering, GISANS: grazing incidence small-angle neutron scattering). Nematic alignment of peptide nanotubes under shear is observed at sufficiently high shear rates under steady shear in either Couette or cone-and-plate geometry. The extent of alignment increases with shear rate. A shear plateau is observed in a flow curve measured in the Couette geometry, indicating the presence of shear banding above the shear rate at which significant orientation is observed (0.1-1 s-1). The orientation under shear is transient and is lost as soon as shear is stopped. GISANS shows that alignment at the surface of a cone-and-plate cell develops at sufficiently high shear rates, very similar to that observed in the bulk using the Couette geometry. A small isotope effect (comparing H2O/D2O solvents) is noted in the CD spectra indicating increased interpeptide hydrogen bonding in D2O, although this does not influence nanotube self-assembly. These results provide new insights into the controlled alignment of peptide nanotubes for future applications.

Fluid dynamic characterization of a polymeric heart valve prototype (Poli-Valve) tested under continuous and pulsatile flow conditions

Purpose Only mechanical and biological heart valve prostheses are currently commercially available. The former show longer durability but require anticoagulant therapy; the latter display better fluid dynamic behavior but do not have adequate durability. New Polymeric Heart Valves (PHVs) could potentially combine the hemodynamic properties of biological valves with the durability of mechanical valves. This work presents a hydrodynamic evaluation of 2 groups of newly developed supra-annular, trileaflet prosthetic heart valves made from styrenic block copolymers (SBC): Poli-Valves. Methods 2 types of Poli-Valves made of SBC and differing in polystyrene fraction content were tested under continuous and pulsatile flow conditions as prescribed by ISO 5840 Standard. A pulse duplicator designed ad hoc allowed the valve prototypes to be tested at different flow rates and frequencies. Pressure and flow were recorded; pressure drops, effective orifice area (EOA), and regurgitant volume were computed to assess the behavior of the valve. Results Both types of Poli-Valves met the minimum requirements in terms of regurgitation and EOA as specified by the ISO 5840 Standard. Results were compared with 5 mechanical heart valves (MHVs) and 5 tissue heart valves (THVs), currently available on the market. Conclusions Based on these results, PHVs based on styrenic block copolymers, as are Poli-Valves, can be considered a promising alternative for heart valve replacement in the near future.