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Heart valve diseases have become one of the main causes for mortality worldwide. To increase the life expectancy of these patients, surgical replacements using mechanical or biological heart valve implants are most commonly used. However, mechanical implants entail the lifelong intake of anticoagulation medication and biological implants exhibit a limited lifetime of 10-20 years. In addition, these implants are limited by their inability to grow with the patient and repair themselves. Hence, the fabrication of tissue engineered heart valve implants that exhibit high mechanical stability while maintaining biocompatibility is strived for. For tissue engineering purposes, hydrogels are a promising candidate for encapsulating cells. In contrast to conventional hydrogels, fibrin hydrogels are auspicious as they are naturally occurring in the human body and provide a three-dimensional environment for cell proliferation and growth. An increase in the mechanical stability of fibrin hydrogels can be achieved through the addition of additives, such as linear reactive copolymers. However, the molecular weight of synthetic copolymers is limited and the long-term degradability and biocompatibility is unknown. Biopolymers such as dextran on the other hand, present a promising option, as they exhibit biocompatible and biodegradable properties combined with tunable molecular weights and affordable production cost.
In this work, we synthesize a hydrogel composed of natural fibrin and dextran hydrogels for the application in tissue engineered heart valve implants. For this purpose, dextran is functionalised with an allyl group using glycidyl methyl ether, which enables hydrogel formation via dithiol addition. The fibrin hydrogel was synthesized through the addition of thrombin and fibrinogen. By varying the concentration of the components and ratio between dextran and fibrin hydrogel, different compositions of fibrin-dextran hydrogels were obtained and analyzed using rheology, scanning electron- and confocal microscopy.
The gelation process and mechanical properties of the fibrin-dextran hydrogel were investigated using rheology. In comparison to the pure fibrin or dextran hydrogel, which only exhibit one gelation point, the rheological data of fibrin-dextran hydrogel mixtures suggests two independent gelation points. Furthermore, a higher storage modulus could be achieved for fibrin-dextran hydrogels in comparison to the pure fibrin hydrogel. The images obtained from Cryo-Scanning Electron Microscopy of the fibrin-dextran hydrogels show a combined structure occurring in typical fibrin and dextran hydrogels. The imaging of stained fibres using confocal microscopy was successful. First experiments on the cell viability of fibrin-dextran hydrogels are currently being conducted.
To conclude, we generated a novel hydrogel composed of fibrin and dextran with excellent mechanical properties and biocompatibility, which shows promising behavior for application in tissue engineered heart valve implants.
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