Anticalcification potential of heparin hydrogel on glutraldehyde fixed bovine pericardial tissues

Valvular heart disease remains common in industrialized countries, because of the decrease in prevalence of rheumatic heart diseases has been accompanied by an increase in that of degenerative valve diseases. Different current available prostheses are being introduced as treatment mainly categorized...

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Bibliographic Details
Main Author: Badria, Adel
Other Authors: Μαυρίλας, Δημοσθένης
Format: Thesis
Language:English
Published: 2019
Subjects:
Online Access:http://hdl.handle.net/10889/12496
Description
Summary:Valvular heart disease remains common in industrialized countries, because of the decrease in prevalence of rheumatic heart diseases has been accompanied by an increase in that of degenerative valve diseases. Different current available prostheses are being introduced as treatment mainly categorized into mechanical or bioprosthetic replacement valves. Both show different pros and cons. A relatively newly proposed treatment for such diseases is tissue engineered heart valves, which still shows some drawbacks mainly calcification. The calcification process consists in the development of calcific deposits on the tissues because of the fact that blood serum is highly supersaturated with respect to calcium phosphate mineral phases. Calcification of tissues may thus be minimized or prevented by the use of anticalcifying agents, i.e. molecules that have the ability to regulate nucleation and/or crystal growth processes. Among different possible anticalcification treatments heparin hydrogel has been selected as the one for our work. Heparin hydrogel offers good space filling material for biological application, charge neutralization of the scaffold in addition to this, cardiologists have a good experience with different effects of heparin for such kind of heart valve replacement surgeries. The work was divided into two main parts: a) Heparin was tested for its effect on the growth of hydroxyapatite (HAP) crystals using Ca/P corresponding to those for supersaturation of HAP. The mechanism of action was further investigated using isotherm adsorption experiment to understand the nature of this inhibition mechanism. b) Heparin was functionalized with thiol group and used to prepare hydrogel, the successfully prepared hydrogel was used as treatment for glutaraldehyde bovine pericardial tissues and calcification potential was tested using constant composition model. The experiments were run under octacalcium phosphate (OCP) supersaturation physiological conditions and the results were analysed histologically, mechanically and using constant composition (CC) model For the first part of the work, Heparin in calcium phosphate solutions showed a clear retardation for the crystal growth process. The inhibition was attributed to adsorption and blockage of the active crystal growth sites and was confirmed by quantitative measurements of the respective adsorption isotherms. For the second part, stable heparin hydrogel was successfully prepared and characterized. Also, the heparin hydrogel treated-glutaraldehyde bovine pericardial tissues (GBPT) showed a clear retardation for the inhibition. Results were confirmed using histological techniques.