Structure-Function Relationship of Heart Valves in Health and Disease

The heart valves allow unidirectional and unobstructed passage of blood without regurgitation, trauma to blood elements, thromboembolism, and excessive stress concentrations in the leaflet and supporting tissue. In order to achieve this, the heart valves rely of their unique macroscale anatomy, histoarchitecture and ultrastructural features that allow them to accommodate repetitive changes in shape and dimension throughout the cardiac cycle. This chapter is focused on the structure-function relationship of the heart valves, with particular focus on the aortic and mitral valves, discussing how the biochemical, histoarchitectural and anatomical features influence valvular function during the cardiac cycle and how valvular function dictates valvular architecture and ECM constitution. The chapter examines the structure-function relationship of valvular tissue by correlating its microscale histoarchitecture and biochemical constitution to its mesoscale biomechanics and macroscale function during the cardiac cycle. Moreover, the chapter examines the influence of pathological alterations on the histoarchitectural and biochemical characteristics of the valves on their biomechanical behavior

Regional biomechanical and histological characterisation of the passive porcine urinary bladder: Implications for augmentation and tissue engineering strategies

The aim of this study was to identify and quantify potential regional and directional variations in the quasistatic uniaxial mechanical properties of the passive urinary bladder wall. Overall, the lower body and trigone regions demonstrated the highest degree of directional anisotropy, whereas the ventral region demonstrated the least directional anisotropy. Significant regional anisotropy was found only along the apex-to-base direction. The dorsal and ventral regions demonstrated a significantly increased distensibility along the apex-to-base direction compared to the other bladder regions, whereas the trigone and lower body regions demonstrated the least distensibility. The trigone, lower body and lateral regions also demonstrated the highest tensile Strength both at regional and directional levels. The study detected significant regional and directional anisotropy in the mechanical properties of the bladder and correlated this anisotropy to the distended and non-distended tissue histioarchitecture and whole organ mechanics. By elucidating the inhomogeneous nature of the bladder, the results from this study will aid the regional differentiation of bladder treatments in terms of partial bladder replacement with suitable natural or synthetic biomaterials, as well as the development of more realistic constitutive models of bladder wall biomechanics and improved computational simulations to predict deformations in the natural and augmented bladder. (c) 2008 Elsevier Ltd. All rights reserved

Development of a dual-component infection-resistant arterial replacement for small-caliber reconstructions: A proof-of-concept study

Introduction: Synthetic vascular grafts perform poorly in small-caliber (<6mm) anastomoses, due to intimal hyperplasia and thrombosis, whereas homografts are associated with limited availability and immunogenicity, and bioprostheses are prone to aneurysmal degeneration and calcification. Infection is another important limitation with vascular grafting. This study developed a dual-component graft for small-caliber reconstructions, comprising a decellularized tibial artery scaffold and an antibiotic-releasing, electrospun polycaprolactone (PCL)/polyethylene glycol (PEG) blend sleeve.Methods: The study investigated the effect of nucleases, as part of the decellularization technique, and two sterilization methods (peracetic acid and γ-irradiation), on the scaffold’s biological and biomechanical integrity. It also investigated the effect of different PCL/PEG ratios on the antimicrobial, biological and biomechanical properties of the sleeves. Tibial arteries were decellularized using Triton X-100 and sodium-dodecyl-sulfate.Results: The scaffolds retained the general native histoarchitecture and biomechanics but were depleted of glycosaminoglycans. Sterilization with peracetic acid depleted collagen IV and produced ultrastructural changes in the collagen and elastic fibers. The two PCL/PEG ratios used (150:50 and 100:50) demonstrated differences in the structural, biomechanical and antimicrobial properties of the sleeves. Differences in the antimicrobial activity were also found between sleeves fabricated with antibiotics supplemented in the electrospinning solution, and sleeves soaked in antibiotics.Discussion: The study demonstrated the feasibility of fabricating a dual-component small-caliber graft, comprising a scaffold with sufficient biological and biomechanical functionality, and an electrospun PCL/PEG sleeve with tailored biomechanics and antibiotic release

Development and characterization of acellular porcine pulmonary valve scaffolds for tissue engineering.

Currently available replacement heart valves all have limitations. This study aimed to produce and characterize an acellular, biocompatible porcine pulmonary root conduit for reconstruction of the right ventricular outflow tract e.g. during Ross procedure. A process for the decellularization of porcine pulmonary roots was developed incorporating trypsin treatment of the adventitial surface of the scraped pulmonary artery and sequential treatment with: hypotonic Tris buffer (HTB; 10mM Tris pH 8.0, 0.1% (w/v) EDTA, 10KIU aprotinin), 0.1% (w/v) SDS in HTB, two cycles of DNase and RNase, and sterilisation with 0.1% (v/v) peracetic acid. Histology confirmed an absence of cells and retention of the gross histoarchitecture. Immunohistochemistry further confirmed cell removal and partial retention of the extra cellular matrix, but a loss of collagen type IV. DNA levels were reduced by more than 96 % throughout all regions of the acellular tissue and no functional genes were detected using PCR. Total collagen levels were retained but there was a significant loss of glycosaminoglycans following decellularization. The biomechanical, hydrodynamic and leaflet kinematics properties were minimally affected by the process. Both immunohistochemical labelling and antibody absorption assay confirmed a lack of α-gal epitopes in the acellular porcine pulmonary roots and in vitro biocompatibility studies indicated that acellular leaflets and pulmonary arteries were not cytotoxic. Overall the acellular porcine pulmonary roots have excellent potential for development of a tissue substitute for right ventricular out flow tract reconstruction e.g. during the Ross procedure

A Comprehensive Comparison of Bovine and Porcine Decellularized Pericardia: New Insights for Surgical Applications

Xenogeneic pericardium-based substitutes are employed for several surgical indications after chemical shielding, limiting their biocompatibility and therapeutic durability. Adverse responses to these replacements might be prevented by tissue decellularization, ideally removing cells and preserving the original extracellular matrix (ECM). The aim of this study was to compare the mostly applied pericardia in clinics, i.e. bovine and porcine tissues, after their decellularization, and obtain new insights for their possible surgical use. Bovine and porcine pericardia were submitted to TRICOL decellularization, based on osmotic shock, detergents and nuclease treatment. TRICOL procedure resulted in being effective in cell removal and preservation of ECM architecture of both species' scaffolds. Collagen and elastin were retained but glycosaminoglycans were reduced, significantly for bovine scaffolds. Tissue hydration was varied by decellularization, with a rise for bovine pericardia and a decrease for porcine ones. TRICOL significantly increased porcine pericardial thickness, while a non-significant reduction was observed for the bovine counterpart. The protein secondary structure and thermal denaturation profile of both species' scaffolds were unaltered. Both pericardial tissues showed augmented biomechanical compliance after decellularization. The ECM bioactivity of bovine and porcine pericardia was unaffected by decellularization, sustaining viability and proliferation of human mesenchymal stem cells and endothelial cells. In conclusion, decellularized bovine and porcine pericardia demonstrate possessing the characteristics that are suitable for the creation of novel scaffolds for reconstruction or replacement: differences in water content, thickness and glycosaminoglycans might influence some of their biomechanical properties and, hence, their indication for surgical use

Multiphysics simulation of the effect of leaflet thickness inhomogeneity and material anisotropy on the stress-strain distribution on the aortic valve

This study developed a realistic 3D FSI computational model of the aortic valve using the fixed-grid method, which was eventually employed to investigate the effect of the leaflet thickness inhomogeneity and leaflet mechanical nonlinearity and anisotropy on the simulation results. The leaflet anisotropy and thickness inhomogeneity were found to significantly affect the valve stress-strain distribution. However, their effect on valve dynamics and fluid flow through the valve were minor. Comparison of the simulation results against in-vivo and in-vitro data indicated good agreement between the computational models and experimental data. The study highlighted the importance of simulating multi-physics phenomena (such as fluid flow and structural deformation), regional leaflet thickness inhomogeneity and anisotropic nonlinear mechanical properties, to accurately predict the stress-strain distribution on the natural aortic valve

Investigation of the suitability of decellularized porcine pericardium in mitral valve reconstruction

International audienceBACKGROUND AND AIM OF THE STUDY: Autologous and glutaraldehyde-treated xenogeneic and homogeneic pericardium has been used extensively in mitral valve repair, but there are a number of limitations associated with its use. These include calcification, limited durability and lack of in vivo regeneration with glutaraldehyde-treated xenografts, as well as the sacrifice of the patient's own pericardium in the case of repair with autologous pericardium. The study aim was to investigate the suitability of decellularized porcine pericardium for heterotopic repair of the mitral valve leaflets, and its potential to regenerate through endogenous cell repopulation in vivo, or in vitro cell seeding prior to implantation. METHODS: Fresh porcine anterior and posterior mitral valve leaflets, together with fresh and decellularized porcine pericardium, were tested histologically, biochemically and biomechanically to investigate potential similarities and differences between the different types of tissue. Subsequently, the decellularized pericardial scaffolds were tested both in terms of biocompatibility, using contact and extract cytotoxicity assays, and in terms of regenerative capacity through porcine mesenchymal stem cell (pMSC) seeding. RESULTS: Histological examination of fresh pericardium and leaflets showed the typical trilaminar and quadlaminar structures of the two tissues, respectively. No cell remnants were observed in the decellularized pericardium, whereas the histoarchitecture of the collagen, elastin and glycosaminoglycan (GAG) matrix appeared well preserved. Significant differences were found in the GAG and hydroxyproline contents and the biomechanics between the leaflet and the pericardial groups. No indication of cytotoxicity was observed with the decellularized pericardial scaffolds. The optimum cell seeding density of pMSCs was 1 x 10(5) cells per cm2, which represented the lowest density at which the cells were capable of repopulating the scaffold by migrating through its full thickness. CONCLUSION: Porcine mitral valve leaflets and porcine fresh/decellularized pericardium shared similar histoarchitectures, but had different biochemical compositions and biomechanics. Decellularized pericardium was shown to be an optimum material for cell repopulation, delivering the necessary biological and biomechanical cues to seeded or migrating cells, and representing a plausible scaffold option for the regeneration of the mitral leaflets in vitro or in vivo, respectively