title: Non-invasive in vivo tracking of fibrin degradation by fluorescence imaging.
abstract: Fibrin-based sealants consist of natural coagulation factors involved in the final phase of blood coagulation, during which fibrinogen is enzymatically converted by thrombin to form a solid-phase fibrin clot. For applications in tissue regeneration, a controlled process of matrix degradation within a certain period of time is essential for optimal wound healing. Hence, it is desirable to follow the kinetics of fibrinolysis at the application site. Non-invasive molecular imaging systems enable real-time tracking of processes in the living animal. In this study, a non-invasive fluorescence based imaging system was applied to follow and quantify site-specific degradation of fibrin sealant. To enable non-invasive tracking of fibrin in vivo, fibrin-matrix was labelled by incorporation of a fluorophore-conjugated fibrinogen component. Protein degradation and release of fluorescence were, in a first step, correlated in vitro. In vivo, fluorophore-labelled fibrin was subcutaneously implanted in mice and followed throughout the experiment using a multispectral imaging system. For the fluorescent fibrin, degradation correlated with the release of fluorescence from the clots in vitro. In vivo it was possible to follow and quantify implanted fibrin clots throughout the experiment, demonstrating degradation kinetics of approximately 16 days in the subcutaneous compartment, which was further confirmed by histological evaluation of the application site.
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology/AUVA Research Centre, Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wolbank
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology/AUVA Research Centre, Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Austria.
authors.forename: Valentin
authors.initials: V
authors.lastname: Pichler
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology/AUVA Research Centre, Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Austria.
authors.forename: James Crawford
authors.initials: JC
authors.lastname: Ferguson
authors.affiliation: Austrian Cluster for Tissue Regeneration, Austria.|Bernhard Gottlieb University School of Dentistry, Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Meinl
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology/AUVA Research Centre, Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Austria.
authors.forename: Martijn
authors.identifier: http://orcid.org/0000-0001-5104-9881
authors.initials: M
authors.lastname: van Griensven
authors.affiliation: Baxter Innovations GmbH, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Goppelt
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology/AUVA Research Centre, Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D004492:Edetic Acid / Q000737:chemistry; D005260:Female; D005337:Fibrin / Q000737:chemistry*; D005342:Fibrinolysis; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence / Q000379:methods*; D008962:Models, Theoretical; D055095:Optics and Photonics; D023822:Tissue Engineering / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D005337:Fibrin; D004492:Edetic Acid
keywords: biomaterial degradation; fibrin; fluorescence; non-invasive imaging