Antibacterial and Biocompatible Coating for Cardiovascular Grafts
In chapter 1: Polyethylene terephthalate (PET) is considered as the gold standard cardiovascular graft to restore the function of damaged vessels and heart valves. However, the post implantation complications essentially distract the long-term patency of PET grafts resulting in prolonged hospitaliza...
Pharmazeutische Technologie und Biopharmazie
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|Summary:||In chapter 1: Polyethylene terephthalate (PET) is considered as the gold standard cardiovascular graft to restore the function of damaged vessels and heart valves. However, the post implantation complications essentially distract the long-term patency of PET grafts resulting in prolonged hospitalization, graft failure, and patient death. Most of the prominent shortcomings of PET are the substantial thrombogenic property and the associated infections as well as the biocompatibility issues. Therefore, in this thesis, the improvement of the biocompatibility and the infection-resistance properties of PET grafts were our foremost perspective. We fundamentally minimized the bacterial adhesion and enhanced the biocompatibility of woven and knitted forms of crimped PET cardiovascular grafts. Our results proved an effective strategy for graft surface modification in terms of biocompatible and infection-resistant. In chapter 2: the initial bacterial adhesion was minimized by a multifunctional network-structured film coat using a newly synthesized amphiphilic SD-PHA-b-MPEO diblock copolymer. A versatile coating technique was described based on the repulsion forces between the surface and the used polymer to preserve the flexibility and tensile ability of crimped PET grafts. The surface modified graft was confirmed by Fourier transform infrared spectroscopy (FTIR) and by scanning electron microscope (SEM). The employed polymer manifested suitable biocompatibility to host cell as established using mouse L929 fibroblast cell line. Importantly, the negative charge and the hydrophobic properties of the polymer augmented the bactericidal effect of the sulfadimethoxine moiety as reported by the significant bacterial anti-adhesion efficiency for Gram-positive S. aureus and Gram-negative E. coli bacteria, and for the previously vein isolated Gram-positive S. epidermidis. In chapter 3: Unlike previous studies, the bacterial adhesion was enzymatically inhibited using a bacterial lytic enzyme, lysozyme. Accordingly, graft with broad-spectrum bacteria-resistant was developed. The lysozyme enzyme was covalently immobilized on PET graft by end-point method and proved by FTIR and X-ray photoelectron spectroscopy (XPS). The activity of immobilized enzyme against M. lysodeikticus cells displayed a significant reduction as compared to the free enzyme. However, the remaining activity remarkably decreased the adhesion of Gram-positive S. epidermidis and S. aureus bacteria and to less extent of Gram-negative E.coli. The anti-adhesion efficiency showed bacterial cells specificity while, showed no significant effect on L929 cells adhesion and growth. This indicated the utility of the employed strategy to modulate the initial bacteria adhesion to inhibit the graft-associated infection. In chapter 4: FITC-dextran loaded Poly lactic-glycolic acid (PLGA) nanoparticles were covalently immobilized onto two different cardiovascular prostheses namely; woven crimped PET and expanded polytetrafluoroethylene (ePTFE, Teflon®). The grafts surface was modified by introduction of amino groups on the surface. The surface modified graft was characterized by electro kinetic analyzer, and FTIR before the covalent coupling to the carboxyl group of PLGA Nanoparticles was performed. The prepared model manifested homogenous monolayer of nanoparticles on grafts surface and displayed a satisfactory stability under appropriate human-mimic continuous flow conditions for 24h. Additionally, the established biocompatibility of nano-coated grafts highlighted the utility of the immobilized nanoparticles on the graft’s surface as an attractive strategy for local drug delivery to treat the common complications after graft’s implantation, and hence increasing the grafts long-term patency. In chapter 5: A thrombus-resistant graft was developed by covalent immobilization of heparin. Additionally, the host cell compatibility of PET grafts was enhanced by co-immobilization of collagen. Heparin and collagen were immobilized by end-point method into previously functionalized PET grafts and characterized using FTIR and XPS. The modified grafts manifested a significant biological activity in-vitro under human-mimic conditions mainly, substantial resistance of the graft to clot and fibrin formation. Importantly, the co-immobilization of heparin and collagen supported the host cell adhesion and growth, and showed synergistic inhibition effect of platelets deposition after continuous flow for 30 minutes to simulate the massive blood flow conditions. Consequently, this approach minimized the inherent thrombogenicity of the PET grafts and the corresponding host response, hence ensuring a rapid coating of grafts with host cells required for the grafts biocompatibility.|
|Physical Description:||150 Pages|