title: Silk fibroin based carrier system for delivery of fibrinogen and thrombin as coagulant supplements.
abstract: The control of bleeding is one of the most important interventions after a traumatic injury. Hemostatic devices delivering blood clotting accelerating agents such as fibrinogen are increasingly used due to their efficacy and their ease of application. In the present study, we describe a method to incorporate the coagulant supplements fibrinogen and thrombin in silk protein sponges by mixing the coagulants with an aqueous silk solution, followed by molding, freeze-drying, and water annealing. In this combination system, we demonstrate the delivery of fibrinogen while maintaining its hemostatic potential. Concentration ratios of silk to fibrinogen of 1.0%/2.8%, 2.3%/1.5%, and 3.0%/0.8% were used. The thrombin-induced fibrin polymeric network filled the space in and next to the silk spongy structure but also remained interconnected to the silk, providing an intact network. The mechanical characterization of the fibrinogen-releasing silk sponges before and after the induction of the fibrinogen polymerization demonstrated that the fibrin network resulted in reduced permanent deformation from 21.1% to 6.5%, 19.6% to 5.7%, and 12.7% to 9.4% for the 2.8%, 1.5%, and 0.8% fibrinogen-containing silk sponges, respectively. Moreover, the fibrin formation lead to a more linear elastic behavior over longer strain ranges. In combination, the Calcein-AM/PI staining and MTT assay results indicate uniform cell adhesion on the surface and cytocompatibility of the silk/fibrin sponges, respectively. Moreover, the co-delivery of thrombin with fibrinogen via silk as carrier material is described, offering a more mechanically robust and durable system while preserving hemostatic features of the coagulant substances for the generation of hemostatic devices. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 687-696, 2017.
authors.affiliation: Department of Biochemical Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria.|Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, 02155, USA.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Andreas H
authors.identifier: 0000-0002-3817-1572
authors.initials: AH
authors.lastname: Teuschl
authors.affiliation: Austrian Cluster for Tissue Regeneration, Vienna, Austria.|Ludwig Boltzmann Institute for Experimental and Clinical Traumatology/AUVA Research Center, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zipperle
authors.affiliation: Department of Biochemical Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Carina
authors.initials: C
authors.lastname: Huber-Gries
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, 02155, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D005340:Fibrinogen / Q000737:chemistry / Q000494:pharmacology; D005349:Fibroins / Q000737:chemistry / Q000494:pharmacology; D006490:Hemostatics / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D013917:Thrombin / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D006490:Hemostatics; D005340:Fibrinogen; D005349:Fibroins; D013917:Thrombin
keywords: fibrinogen; hemostatic device; silk; thrombin