title: Tranexamic acid--an alternative to aprotinin in fibrin-based cardiovascular tissue engineering.
abstract: 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 (trans-4-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 microg/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 microg/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.
authors.affiliation: Department of Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Cholewinski
authors.forename: Maren
authors.initials: M
authors.lastname: Dietrich
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Flanagan
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitz-Rode
authors.forename: Stefan
authors.initials: S
authors.lastname: Jockenhoevel
mesh_terms: D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D007611:Aprotinin / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005337:Fibrin; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D013718:Tensile Strength / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D014148:Tranexamic Acid / Q000008:administration & dosage*
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid; D005337:Fibrin; D007611:Aprotinin