Synthesis and characterization of siloxane poly(urethane-urea)s for cardiovascular applications

Dandeniyage, L 2019, Synthesis and characterization of siloxane poly(urethane-urea)s for cardiovascular applications, Doctor of Philosophy (PhD), Science, RMIT University.

Document type: Thesis
Collection: Theses

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Title Synthesis and characterization of siloxane poly(urethane-urea)s for cardiovascular applications
Author(s) Dandeniyage, L
Year 2019
Abstract Currently there are two types of synthetic heart valves, mechanical and bioprosthetic, each with certain disadvantages. The mechanical valve requires the patient to take anticoagulation drugs regularly and the durability of the bioprosthetic valve is relatively poor. A synthetic heart valve with better durability and biocompatibility is required to overcome the deficiencies of existing valves. Polyurethanes (PU) have been investigated in cardiovascular applications due to their exceptional biocompatibility, stability, and mechanical performance. Elast-EonTM 2A is a siloxane-based PU developed by CSIRO and commercialized by St. Jude medical (Abbott) for cardiac pacemaker lead insulations. Over 4 million pacemaker leads have
been implanted in patients globally since it was introduced in 2006 and there is no reported insulation failure. Although mechanical properties of Elast-EonTM 2A are suitable for a range of medical implants, materials for synthetic heart valves require high tensile strength, high tear strength and low cyclic creep for long term performance. Therefore, this study was aimed at developing a superior material with suitable mechanical properties and biostability for synthetic heart valve applications and understanding their structure-property-biostability relationship. PU are comprised of non-polar soft segment and polar hard segment bonded chemically in alternating sequence. Mechanical properties of PU are influenced by phase separation between soft and hard segments triggered by their incompatibility. This study proceeded by hypothesising that introduction of polar functionality into the soft segment can improve the compatibility with relatively polar hard segment. This improved compatibility would then improve the creep resistance, tensile and tear strengths, while retaining long-term biostability.

At the first stage of this study, a series of linked-macrodiols was synthesised by linking poly(hexamethylene oxide) (PHMO) and α,ω-bis(6-hydroxyethoxypropyl) poly(dimethylsiloxane) (PDMS) individually with different diisocyanates. Incorporation of
diisocyanate in the soft segment increases the polarity and hence improve the compatibility with the hard segment. 4,4’-methylenediphenyl diisocyanate (MDI), isophorone diisocyanate (IPDI) and hexamethylene diisocyanate (HDI) were used to link macrodiols. Those linked macrodiols were used in synthesising a series of mixed macrodiol based siloxane poly(urethaneurea)s (SiPUU). The hard segment was composed of MDI, and a 1:1 mixture of 1,3-bis(4-hydroxybutyl)-1,1,3,3-etramethyldisiloxane (BHTD) and 1,2-ethylenediamine (EDA). It was xxi found that the linking of PHMO with MDI and IPDI produced SiPUU with higher creep resistance and higher tensile and tear strengths compared to Elast-EonTM 2A. These SiPUU were characterized using a suit of analytical methods including Fourier transform infrared spectroscopy, gel permeation chromatography, differential scanning calorimetry, dynamic mechanical analysis, thermogravimetric analysis, X-ray photoelectron spectroscopy, atomic force microscope, small and wide-angle X-ray scattering. The urethane linkages introduced to the soft segment by linking PHMO with MDI and IPDI formed stronger hydrogen bonds with urethane and urea linkages in the hard segment compared to that in Elast-EonTM 2A. These strong interactions enhanced the compatibility between soft and hard segments resulting in improved mechanical properties. Furthermore, PHMO-MDI-PHMO and PHMO-IPDI-PHMO linked macrodiols contributed to the mixedphase of SiPUU together with end groups of PDMS and some parts of hard segment. The linking of PHMO with MDI or IPDI reinforced this interface between soft and hard segments giving rise to better mechanical properties on the resultant SiPUU. All the SiPUU were noncytotoxic and showed siloxane-rich hydrophobic surfaces with negligible water uptake (0.7%/dry mass). Oxidative stability of two SiPUU synthesised with PHMO-MDI-PHMO and PHMOIPDI-PHMO linked macrodiols was evaluated by using accelerated in vitro oxidative method with 20% H2O2 and 0.1 mol/L CoCl2 solution which simulated the environment of human body.

Evaluation of molecular weight, physical and chemical properties of these two materials after the oxidative treatment showed similar degree of resistance to environmental stress cracking (ESC) compared with Elast EonTM 2A. However, they showed improved resistance to ESC compared to polyether-PU. This study confirmed that the chemical modification in the soft segment did not affect the oxidative stability of SiPUU while retaining their high mechanical performance and long-term stability. Another series of SiPUU was synthesised by varying EDA:BHTD ratio. The optimum content of chain extender composition in the hard segment was found to be in the range of 40 to 60-mol% BHTD in terms of higher mechanical properties. The soft segment of this series was comprised of PDMS and PHMO-MDI-PHMO linked macrodiol. This formulation produced SiPUU with high tear and tensile strengths, low modulus, high elongation and good oxidative stability.

This study provides the underpinning science together with optimised process protocols to design and synthesise SiPUU with high mechanical properties and good biostability for cardiovascular applications. Furthermore, this study provides greater insights on the structureproperty-biostability relationship of the synthesised SiPUU. Thus, this study has advanced the science of producing SiPUU polymers which have superior mechanical and biostability performance than those available commercially for heart valve leaflets. The science and technological process developed in this study can also be applied to formulate polymers suitable for other medical devices.
Degree Doctor of Philosophy (PhD)
Institution RMIT University
School, Department or Centre Science
Subjects Food Sciences not elsewhere classified
Chemical Characterisation of Materials
Keyword(s) Poly(urethane urea)
Oxidative stability
Invitro degradation
Medical devices
Linked macrodiol
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Created: Thu, 20 Jun 2019, 08:42:36 EST by Adam Rivett
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