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.

An Injectable Hybrid Gelatin Methacryloyl (GelMA)/Phenyl Isothiocyanate-Modified Gelatin (Gel-Phe) Bioadhesive for Oral/Dental Hemostasis Applications

“…Many studies have shown various materials such as fibrin-/silk- [ 15 ], polysaccharide- [ 16 ], and collagen-based adhesives [ 17 ], which can be used as soft hydrogels for hemostasis. Collagen is one of the essential extracellular matrices in gingival tissues [ 18 ].…”

Silk fibroin photo-lyogels containing microchannels as a biomaterial platform for in situ tissue engineering

“…15,16 A few reports of silk based lyogels have been published and it has been demonstrated that the crosslinked nature of the starting protein network results in unique physicochemical properties compared to lyophilized sponges made by lyophilizing uncrosslinked silk solution. 14,[16][17][18][19] While lyophilized silk sponges have been widely explored and evaluated for applications such as soft tissue, [20][21][22] intervertebral disc, 23 and cardiovascular tissue [24][25][26] augmentation and regeneration, platelet production, 27 and drug delivery, 28,29 silk lyogels are less well characterized. In particular, the properties of silk lyogels made from di-tyrosine crosslinked silk networks have not been explored to date.…”

Cyclic RGD functionalized PLGA nanoparticles loaded with noncovalent complex of indocyanine green with urokinase for synergistic thrombolysis

“…Most reported co-loaded nanoparticles have difficulty controlling the synergistic release of two or more payloads, which has a great impact on the outcomes of synergistic therapies ( Teuschl et al, 2017 ; Zhu et al, 2018 ). Herein, the PLGA nanoparticles loaded with preformed ICG@uPA realized adjustable proportion of components and synchronous release of the payloads, which meant that the NPs could serve as a suitable platform for tunable and synergistic thrombolysis via the administration of ex vivo laser.…”