Journal
TISSUE ENGINEERING PART A
Volume 15, Issue 11, Pages 3645-3653Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2009.0235
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Funding
- Fordergemeinschaft Deutsche Kinderherzzentren e.V
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Recent clinical trials have led to the worldwide suspension of aprotinin, the most commonly used antifibrinolytic agent in fibrin-based tissue engineering. For future clinical applications of fibrin-based scaffolds, a suitable, alternative fibrinolysis inhibitor must be identified. The present study aimed to evaluate tranexamic acid (trans4-aminomethyl-cyclohexane-1-carboxylic acid [t-AMCA]) as an alternative fibrinolysis inhibitor to aprotinin for cardiovascular tissue engineering applications. The effects of various concentrations of t-AMCA (30-160 mu g/mL) and aprotinin on fibrin gel-lysis were spectrophotometrically quantified in vitro. Cytotoxic effects of t-AMCA and aprotinin on carotid artery-derived cells, in addition to their influence on fibrin gel mechanical strength, were examined. Further, the influence of t-AMCA versus aprotinin on three-dimensional fibrin-based constructs was analyzed using light microscopy, scanning electron microscopy, and transmission electron microscopy. The results demonstrated that neither t-AMCA (30-160 mu g/mL) nor aprotinin elicited cytotoxic effects on cultured cells. Although aprotinin showed reduced fibrinolysis in the presence of plasmin compared to t-AMCA, no significant difference was obtained under standard culture conditions. Additionally, t-AMCA had no negative influence on the mechanical stability of fibrin gels, which also demonstrated excellent cell morphology, tissue development, and ultrastructure. The results from the present study demonstrate that t-AMCA may be a suitable alternative to aprotinin for controlling the in vitro degradation rate of fibrin-based tissue-engineered constructs.
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