Among these, fibrin has been studied extensively to understand the basic mechanisms of viscoelasticity as well as molecular mechanisms of coagulation disorders. Influence of a natural and a synthetic inhibitor of factor xiiia on fibrin clot rheology esther a. Rheological characterization and dissolution kinetics of fibrin gels crosslinked by a microbial transglutaminase article in biopolymers 775. Rheological characterization and dissolution kinetics of. Concentration independent modulation of local micromechanics.
Gel elasticity is proportional to fibrinogen concentration but shows a nonlinear dependence on transglutaminase. Keenera,b departments of mathematicsa and bioengineeringb university of utah 155 south 1400 east, room 233 salt lake city, ut 841120090 received on 16 september 16 2005. Characterization of fibrin and collagen gels for engineering. Because of its regenerative ability and biodegradable nature 42, fibrin gel is. May 19, 2010 fibrin gels are responsible for the mechanical strength of blood clots, which are among the most resilient protein materials in nature. Structurefunction relationships of selfassembled fibrillar gels. We observe that the protein polymorphism in the gel becomes spatially heterogeneous on a micrometer.
A modification of this strategy is to replace the collagen gel with a fibrin gel 16. To enhance the strength of the fibrin gel, a combination strategy can be employed whereby a highly porous synthetic polymer scaffold with appropriate mechanical properties is filled with chondrocytes suspended in a fibrin gel and this whole construct is implanted at the desired junction eyrich et al. A reproducible, high throughput method for fabricating. Caton linking fibrin clot structure, rheology and embolisms 16.
Hydrogels are used for 3d in vitro assays and tissue engineering and regeneration purposes. Hypofibrinolysis is a risk factor for arterial thrombosis at young. Precise placement the duplospray system allows for bleeding to be targeted laparoscopically by getting as close as 25 cm to the tissue. Here we investigate the physical origin of this mechanical behavior by performing rheology measurements on reconstituted fibrin gels. Pdf rheological properties of magnetic biogels researchgate. We find that increasing levels of shear strain induce a succession of distinct elastic responses that reflect stretching. The gels were characterized through their rheological properties. We developed a high throughput method for creating fibrin gels using molds fabricated from polydimethylsiloxane pdms. For a thorough interpretation of this technology, an integral biomechanical characterization of the materials is required. Fibrin gel, polymer fibrils generated from thrombincleaved fibrinogen, is known to trap a variety of angiogenic factors such as bfgf and vegf to accelerate angiogenesis in vivo 40,41.
Fibrin clot structure and function arteriosclerosis. Scaffold architecture and fibrin gels promote meniscal. A twostep fibrinogenfibrin transition in blood coagulation. Apr 05, 2005 various fibrin gels were prepared with a microbial transglutaminase under miscellaneous conditions. Fibrin gels are among the most resilient polymer gels in nature. The uppermost layer has maximum velocity while the bottom layer is stationary. The influence of fibronectin addition and that of covalent bonding on the viscoelastic characteristics were evaluated. Influence of fibrinogen concentration in fibrin gels on youngs modulus department of biomedical enginee ring 2 abstract for tissue engineering a heart valve, the idea has risen to combine the advantages of polycaprolactone and fibrin by using the first as a mechanical backbone and the latter as a celldelivery substance surrounding the backbone. Request pdf structure of high density fibrin networks probed with neutron scattering and rheology the structural and mechanical properties of coarse fibrin networks formed in d2o solutions are. The rigidity of the fibrin gel at the saturation of clotting decreased with the increase of shear rate of measurement above about 0.
Fibrin, the structural component of a blood clot, is formed by polymerization of fibrinogen, a megamonomer molecular weight 340 000 present in blood plasma at a. Thermoresponsive stiffening with microgel particles in a. During the early stages of the wound healing process, a loose platelet plug is stabilized by the formation of a fibrin gel matrix. The fine nanostructure of fibrin clots at and after the gel point has been characterized using precise biophysical techniques that showed dynamic behavior and complex hierarchy at different scales. Local and global deformations in a strainstiffening fibrin gel view the table of contents for this issue, or go to the journal homepage for more. One aspect of fibrin gel rheology that is not observed in most polymeric systems is strain hardening. The loss of this small peptide is not sufficient to make the resulting fibrin molecule insoluble, but it tends to form complexes with adjacent fibrin and fibrinogen molecules. Sep 18, 2008 2005 fibrin gelimmobilized primary osteoblasts in calcium phosphate bone cement. Thrombin generation is a dynamic, localized process, and the formation of fibrin is determined by cellular procoagulant activity, which leads to spatial heterogeneity in clot structure associated with the distance of fibrin from the cell surface. Department of biomedical engineering, northwestern university, evanston, illinois 60208. Because of its regenerative ability and biodegradable nature 42, fibrin gel is widely used in the field of tissue engineering.
Using rheology to characterize flow and viscoelastic. Fibrin gels are responsible for the mechanical strength of blood clots, which are among the most resilient protein materials in nature. The scaffold consists of naturally occurring biomaterials composed of a crosslinked fibrin network and has a broad use in biomedical applications. The application of large amplitude oscillatory stress in a.
Influence of fibrinogen concentration on the youngs. Thrombin then cleaves a second peptide fibrinopeptide b, from fibrin and the fibrin monomers formed then polymerize spontaneously to form an insoluble gel. A reproducible, high throughput method for fabricating fibrin. Low density fibrin gels have a straindependent rheology characterized by several elastic regimes. Factin, fibrin, collagen, vimentin, and polyacrylamide.
Most studies of fibrin gel rheology have been conducted on gels derived. Fibrin gel as an injectable biodegradable scaffold and. Current meniscal tissue engineering is inadequate, as the signals for increasing meniscal cell proliferation have not been established. Fibrin gel exhibits excellent biocompatibility, promotes cell attachment, and can degrade in a controllable manner. Sol gel transition represents the transformation from liquid state sol to the solid state gel and the gel point is the critical transition point. It is advantageous opposed to synthetic polymers and collagen gels when cost, inflammation, immune response, toxicity and cell adhesion are concerned. Fibrin gels are a promising biomaterial for tissue engineering. Influence of fibrinogen concentration on the youngs modulus. Based on this structural evidence, we study the rheology of fibrin gels with the aim. Characterization of rheological properties and degradation of. Pdf we report an experimental and theoretical study of the rheological.
The origins of clot rheological behavior associated with network morphology and factor xiiiainduced crosslinking were studied in fibrin clots. It has been foung that if the measuring shear rate is lower than about 0. An important tool for studying cellmatrix interactions is the cell populated collagen gel 1,2. In situ neutron scattering study of structural transitions in fibrin networks under shear deformation summer school on the fundamentals of neutron scattering sans team nist center for neutron research jun 1823, 2012 abstract fibrin is the major protein component of blood clots, forming a crosslinked network of fibers and is important in the. Biological macromolecules have unique rheological properties that distinguish them from common synthetic polymers. Coagulation culminates in the production of thrombin, which converts fibrinogen into fibrin, forming the blood clot, to stop bleeding. Production of clots with abnormal structure and stability has been demonstrated in plasma samples from patients with increased cardiovascular disease risk. Liard jet instability of a shearthickening concentrated. The gel provides a 3d environment that is closer to the in vivo character of the tissue and better suited for understanding cell behavior than is offered by traditional 2d cultures 3. For shear flow to take place a shear force must act on the fluid. Winner rheological and turbidimetric characterization of. Native fibrin gel networks and factors influencing their formation in health and disease.
May 19, 2010 fibrin is the main structural protein in blood clots, which stop bleeding and serve as scaffolds to promote wound repair. Shear modulus, creep, and creep recovery of fine unligated clots. To maintain gel hydration, 2 ml of pbs or media were added to the dish after gelation. Bottom inset the local rheology is measured by microrheology. Fibrin gel, a biopolymeric material, provides numerous advantages over synthetic materials in functioning as a tissue engineering scaffold and a cell carrier. We incorporated colorectal cancer sw620 and gastric cancer mkn74 cells within a bonemimicking microfluidic platform consisting of an ha fibrin composite and investigated their viability. It is produced naturally by the body after injury, but also can be engineered as a tissue substitute to speed healing. Fibrin gel is able to function as both twodimensional and threedimensional cell culture scaffold. There is a pressing need to develop new and consistent approaches for producing fibrinbased hydrogels for examination.
Stability of the knee relies on the meniscus, a complex connective tissue with poor healing ability. Rheological measurements of fibrin gels during clotting. Fibrin hydrogels prepared from different fibrinogen concentrations 12. Over time the fibrin is degraded and replaced with cellsynthesized ecm that follows the initial fibrin fiber alignment pattern. Implantation of fibrin gel on mouse lung to study lung. Rheological and turbidity study of fibrin hydrogels. Quantitative measurements of network features fiber lengths. Structure and rheology of fibrin networks springerlink.
In this study, collagen scaffold structure, isotropic or aligned, and fibrin gel addition were tested. The fibrin gel develops a similar alignment pattern as a collagen gel during compaction. A polymeric gel is a 3d network generating from flexible chains through physical or chemical interactions. Thrombin and fibrinogen impact clot structure by marked. Fibrin networks strainstiffen both in shear and tension before investigating the structural properties of fibrin hydrogels using bcars, we measured the viscoelastic properties of our hydrogels with shear rheometry and tensile testing. Precise placement the duplospray system allows for bleeding to be targeted laparoscopically by getting as. Structurefunction relationships of selfassembled fibrillar gels kathleen m. Upon vascular injury, fibrin polymerizes to form a fibrous gel that can withstand the forces exerted by flowing blood and by embedded cells 2, 3. Incubate with the lid facing up in the hood for a minimum of 20 minutes. Previous studies have shown that a genipin cross linked fibrin hydrogel satisfies the three basic requirements for a good af sealant. Using rheology to characterize flow and viscoelastic properties of hydrogels, adhesives and biopolymers tianhong terri chen phd senior applications scientist. Fibrin gel as an injectable biodegradable scaffold and cell. Structural origins of fibrin clot rheology esther a.
In situ neutron scattering study of structural transitions in. In this study, we analyzed the gel rheology of an hafibrin composite to assess the influence of the mechanical properties of the ecm on the tme. Fibrin gels are among the most resilient polymer gels in nature 4, 5. Fibrinogen and fibrin in hemostasis and thrombosis. Parallel plate rheology curing and mechanical characterization of. Fibrin gel rheology 53 figure 5 shows our recent results for the shear rate dependence of the saturated values of rigidity, g and gs, which have been obtained by ver. Local and global deformations in a strainstiffening.
There is a pressing need to develop new and consistent approaches for producing fibrin based hydrogels for examination. Treatment of dermal wounds and development of new techniques by which dermal wound healing can be accelerated with minimal scarring are of global interest. Ewoldt 1,4,5 1 department of mechanical science and engineering, university of illinois at urbanachampaign, urbana, il, 61801 2 department of chemistry, university of. After the gelation of fibrin gel, isolated cells are seeded into the surface of fibrin gel. Applications of injectable fibrin gel as scaffolds in tissue engineering. Villone computational oscillatory rheometry of rigid particle suspensions at finite inertia nf11 m. Fibrin scaffold is an important element in tissue engineering approaches as a scaffold material. The suitability of controlled stress large amplitude oscillatory shear laostress for the characterisation of the nonlinear viscoelastic properties of fully formed fibrin clots is investigated. In situ neutron scattering study of structural transitions.
Fibrin hydrogels can support large macroscopic strains owing to the unfolding transition of. Structural origins of fibrin clot rheology sciencedirect. Structural origins of fibrin clot rheology pubmed central pmc. Structure of high density fibrin networks probed with. Prestrain sweeps on both partially crosslinked fibrin samples defined here as fibrin gels polymerized.
Weigandt a dissertation submitted in partial fulfillment of the requirement for the degree of doctor of philosophy university of washington 2012 reading committee. Network morphology was manipulated by varying the concentrations of fibrinogen, thrombin, and calcium ion, and crosslinking was controlled by a synthetic, activecenter inhibitor of fxiiia. Blomback b, banerjee d, carlsson k, hamsten a, hessel b, procyk r, silveira a, zacharski l. Local and global deformations in a strainstiffening fibrin gel. Strain hardening of fibrin gels and plasma clots springerlink. A fibrin scaffold is a network of protein that holds together and supports a variety of living tissues. Fibrin gels are responsible for the mechanical strength of blood clots, which are. Observing and quantifying fibroblastmediated fibrin gel. Solgel transition represents the transformation from liquid state sol to the. We incorporated colorectal cancer sw620 and gastric cancer mkn74 cells within a bonemimicking microfluidic platform consisting of an hafibrin composite and investigated their viability. Regarding altered fibrin clot structure and function in individuals with intermittent claudication.
In this work, we characterize the mechanical and functional behavior of two specific hydrogels that play critical roles in wound healing, collagen and fibrin. As shown in figure 3a, the traditional twodimensional scaffold is fabricated before cell seeding. A twostep fibrinogen fibrin transition in blood coagulation. Fibrin is the main structural protein in blood clots, which stop bleeding and serve as scaffolds to promote wound repair. Keywords fibrin polymer magnetic gels structural transformations.
However, current fabrication methods are time intensive with inherent variation. Using rheology to characterize flow and viscoelastic properties of hydrogels, adhesives. Local hemostatic blood products in hemophilia care. Various fibrin gels were prepared with a microbial transglutaminase under miscellaneous conditions.
Structural hierarchy governs fibrin gel mechanics ncbi nih. Early studies in which fibroblasts were homogenously distributed within a collagen gel found that the cells rapidly. Microscale spatial heterogeneity of protein structural. In this study, we analyzed the gel rheology of an ha fibrin composite to assess the influence of the mechanical properties of the ecm on the tme. Tisseel is the only fibrin sealant to offer a complete portfolio of drip and spray applicators, allowing surgeons to select the right tools to address individual patient needs. A fibrin gel is formed when the protein fibrinogen is enzymatically cleaved by thrombin and crosslinked by. Capturing the rich nonlinear viscoelastic behaviour of the fibrin network is important for understanding the structural behaviour of clots formed in blood vessels which are exposed to a wide range of. Strain stiffening behavior is observed in the crosslinked biopolymer networks. Sterilize the fibrin plate by spraying 70% ethanol 4 times into the cap of the plate and allowing the ethanol to cover the plate. Metabolic activity was promoted by fibrin addition.
764 1101 1547 1432 529 1130 1111 893 1245 914 112 942 871 986 957 108 308 772 224 594 731 1286 1303 410 386 702 491 1007 489 1517 834 424 1211 432 659 683 554 301 1416 574 915