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

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

Polymeric Scaffolds for Bioartificial Cardiovascular Prostheses

The reconstruction or replacement of diseased heart valves, the revascularisation of coronary arteries by coronary artery bypass grafting, the replacement of the central or peripheral blood vessels, and the reconstruction of the irreversibly damaged heart muscle represent the most common fields of application of cardiovascular surgery. In such cases, the diseased tissue is replaced by either a synthetic (metallic or polymeric) or a biological (xenograft, homograft, or autograft) prosthesis, or tissue engineered constructs. The aim of this book chapter is to give an overview over the most frequently used synthetic and biologic polymers as scaffold material in cardiovascular surgery

Proteomics Characterization of Extracellular Space Components in the Human Aorta

The vascular extracellular matrix (ECM) is essential for the structural integrity of the vessel wall and also serves as a substrate for the binding and retention of secreted products of vascular cells as well as molecules coming from the circulation. Although proteomics has been previously applied to vascular tissues, few studies have specifically targeted the vascular ECM and its associated proteins. Thus, its detailed composition remains to be characterized. In this study, we describe a methodology for the extraction of extracellular proteins from human aortas and their identification by proteomics. The approach is based on (a) effective decellularization to enrich for scarce extracellular proteins, (b) successful solubilization and deglycosylation of ECM proteins, and (c) relative estimation of protein abundance using spectral counting. Our three-step extraction approach resulted in the identification of 103 extracellular proteins of which one-third have never been reported in the proteomics literature of vascular tissues. In particular, three glycoproteins (podocan, sclerostin, and agrin) were identified for the first time in human aortas at the protein level. We also identified extracellular adipocyte enhancer-binding protein 1, the cartilage glycoprotein asporin, and a previously hypothetical protein, retinal pigment epithelium (RPE) spondin. Moreover, our methodology allowed us to screen for proteolysis in the aortic samples based on the identification of proteolytic enzymes and their corresponding degradation products. For instance, we were able to detect matrix metalloproteinase-9 by mass spectrometry and relate its presence to degradation of fibronectin in a clinical specimen. We expect this proteomics methodology to further our understanding of the composition of the vascular extracellular environment, shed light on ECM remodeling and degradation, and provide insights into important pathological processes, such as plaque rupture, aneurysm formation, and restenosis

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

Metabolic assessment of therapies for the development of drug-eluting stents

Metabolic assessment of therapies for the development of drug-eluting stent

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

Coaxial electrospinning as a process to engineer biodegradable polymeric scaffolds as drug delivery systems for anti-inflammatory and anti- thrombotic pharmaceutical agents

Objective: Blend electrospinning has been acknowledged as a cost-effective technique for the production of fibrous scaffolds, suitable for various biomedical applications. Coaxial electrospinning is a method variant that results in core-shell structures with advantages, such as delayed diffusion and protection of sensitive biomolecules. The aim of this work was to evaluate how different process and solution parameters affect the structural, mechanical and physical properties of the fibers, created by polycaprolactone (PCL). In addition, acetylsalicylic acid (ASA) that was used as a model anti-inflammatory and anti-thrombotic agent, was loaded within the fiber meshes in order to compare release kinetics between fibers produced by conventional blend and coaxial electrospinning. Methods: Scanning electron microscopy (SEM) was used to investigate the structural and morphological characteristics of the fibers. The fibers’ hydrophilicity was investigated using contact angle measurements while the electrical conductivity of the polymeric solutions and the thermal properties of the fibers were also evaluated. Differential scanning calorimetry (DSC) was used to determine the fibers’ melting point and mechanical tensile tests were performed in order to study the mechanical properties of the fibers. Moreover, UV-vis spectroscopy was used to determine the release kinetics of ASA. Results: The results indicated that increasing the concentration of PCL led to thicker and less aligned fibers. Furthermore, the physicochemical characterization did not reveal significant changes during the process. Coaxially electrospun fibers that were loaded with ASA exhibited a slower and sustained, biphasic release profile compared to blend electrospun fibers with 34% of ASA released during the first 8h and 97% in total after 3 months. Conclusion: Taken together, fibrous meshes created by coaxial electrospinning using PCL, can be tailor-made by a careful optimization of all the process and solution parameters, in order to fit the scope of specific applications in the fields of biomedical engineering and drug delivery