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Heart valve replacement or repair has become an increasingly popular surgical intervention for chronic heart valve disease. The mitral valve's complex geometry and integration into the left ventricle make repair to the valve's parts more attractive than total valve replacement. This study investigated the deformations of the mitral valve using mathematical models. The calculated deformation will be used to optimise bioreactors used in the creation of tissue engineered replacement mitral valve parts. The constitutive make up of the valve was investigated at both the micro-scale using histological techniques and at the macro-scale using uniaxial tensile tests. This investigation showed that collagen fibres were mainly aligned circumferentially and that elastin fibres were aligned both radially and circumferentially in the leaflets which had the effect of making the leaflets less extensible in the circumferential direction. The chordae showed axial collagen fibre alignment with thinner chordae exhibiting less extensibility. The leaflet materials were modelled using a strain energy formulation for two fibre families. This formulation showed a better fit to experimental data for biaxial tests (May- Newman & Yin 1995; Grashow et al 2006) when compared to available constitutive models in LSDYNA. The complex 3D geometry of the valve was captured using micro-computed tomography in conjunction with geometry extraction codes written in MATLAB (MathWorks) and computer aided design package SolidWorks (Dassault Systeme). The reconstructed geometry highlighted the asymmetrical nature of chordae origins and insertions, along with the asymmetry of the leaflets free edge. The geometry and the constitutive model was brought together in a finite element model. The annular deformation was then modelled using an elastic boundary method to obtain 15% and 25% saddle height ratios (SVR). With the 25% SVR model showing reduced strains in the anterior leaflet at peak systole. Finally the strains for the central regions of the anterior leaflet were compared to the strains generated in a model of a pericardium patch bioreactor. It was shown that the 5th and 8th bioreactor settings came closest to replicating the strains reported in the mitral valve finite element models.

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Introduction: A third of patients needing arterial bypass grafts lack sufficient autologous vessels. Prosthetic alternatives - principally PTFE and Dacron - have poor patency rates because of compliance mismatch with elastic arteries and inherent surface thrombogenicity. The aim of this research was to develop - for the first time - a hybrid tissue-engineered bypass graft consisting of an elastic scaffold of compliant poly(carbonate-urea)urethane (CPU), incorporated with human smooth muscle cells (SMC) and endothelial cells(EC).;Methods: 1) Methods of human vascular SMC and EC extraction were assessed for both saphenous vein and umbilical cord vessels. 2) Extracted cells were assessed by immunostaining and for SMC the ability to contract collagen gels. 3) Coating CPU with various biomolecules (to make the surface bioactive), cell seeding density and attachment period were assessed for their impact on SMC attachment. 4) Cell growth on CPU was investigated by retroviral transduction of the GFP (Green Fluorescent Protein) gene and assays of cell viability and nucleic acid content. 5) A bioreactor and pulsatile flow circuit was developed for long-term culture of cells on CPU. 6) The impact of shear stress pre-conditioning on cell retention on the hybrid bypass graft was investigated under arterial flow conditions.;Results: 1) SMCs were reliably extracted from umbilical cord and saphenous vein. ECs were only reliably extracted from umbilical cord. 2) Cord SMCs grew faster than saphenous vein SMCs (doubling time of 3.4+0.6 days against 5.6+1.9 days p = 0.0227): all SMCs stained for alpha-actin and contracted collagen gels 3) SMC attachment to CPU was significantly enhanced by Fibronectin-like Engineered Polymer Protein Plus FEPP+ (from 20.7+4.6% to 31.5 5.9%: pO.Ol), higher cell density but not longer attachment period. 4) Transducing SMCs with GFP successfully allowed live cell imaging on CPU and assays of both viable cells and nucleic acid confirmed cell growth on CPU. 5) The flow circuit successfully allowed long-term sterile culture of cells on CPU. 6) Retention of SMCs and ECs on CPU was improved by a period of shear stress pre-conditioning: from 56.7+7.0% to 76.2+6.5% SMC retention and from 45.6+2.3% to 67.4+4.0% EC retention (p < 0.03). Conclusion: Pre-lining CPU with FEPP+ enhances SMC attachment. GFP-transduction allows study of SMC growth on CPU. Pre-conditioning enhances retention of SMCs and ECs onto CPU, probably because the mechanical stimuli orientate the cells and increase the release of matrix proteins and attachment factors. The stage is now set for developing a hybrid graft for in vivo studies.

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