Mechanics and microstructure of blood plasma clots in shear driven rupture.

Intravascular blood clots are subject to hydrodynamic shear and other forces that cause clot deformation and rupture (embolization). A portion of the ruptured clot can block blood flow in downstream vessels. The mechanical stability of blood clots is determined primarily by the 3D polymeric fibrin network that forms a gel. Previous studies have primarily focused on the rupture of blood plasma clots under tensile loading (Mode I), our current study investigates the rupture of fibrin induced by shear loading (Mode II), dominating under physiological conditions induced by blood flow. Using experimental and theoretical approaches, we show that fracture toughness, i.e. the critical energy release rate, is relatively independent of the type of loading and is therefore a fundamental property of the gel. Ultrastructural studies and finite element simulations demonstrate that cracks propagate perpendicular to the direction of maximum stretch at the crack tip. These observations indicate that locally, the mechanism of rupture is predominantly tensile. Knowledge gained from this study will aid in the development of methods for prediction/prevention of thrombotic embolization.

Cracks in tensile-contracting and tensile-dilating poroelastic materials.

Fibrous gels such as cartilage, blood clots, and carbon-nanotube-based sponges with absorbed oils suffer a reduction in volume by the expulsion of liquid under uniaxial tension, and this directly affects crack-tip fields and energy release rates. A continuum model is formulated for isotropic fibrous gels that exhibit a range of behaviors from volume increasing to volume decreasing in uniaxial tension by changing the ratio of two material parameters. The motion of liquid in the pores of such gels is modeled using poroelasticity. The direction of liquid fluxes around cracks is shown to depend on whether the gel locally increases or decreases in volume. The energy release rate for cracks is computed using a surface-independent integral and it is shown to have two contributions - one from the stresses in the solid network, and another from the flow of liquid. The contribution to the integral from liquid permeation tends to be negative when the gel exhibits volume decrease, which effectively is a crack shielding mechanism.

Fracture toughness of fibrin gels as a function of protein volume fraction: Mechanical origins.

The mechanical stability of blood clots necessary for their functions is provided by fibrin, a fibrous gel. Rupture of clots leads to life-threatening thrombotic embolization, which is little understood. Here, we combine experiments and simulations to determine the toughness of plasma clots as a function of fibrin content and correlate toughness with fibrin network structure characterized by confocal and scanning electron microscopy. We develop fibrin constitutive laws that scale with fibrin concentration and capture the force-stretch response of cracked clot specimens using only a few material parameters. Toughness is calculated from the path-independent J* integral that includes dissipative effects due to fluid flow and uses only the constitutive model and overall stretch at crack propagation as input. We show that internal fluid motion, which is not directly measurable, contributes significantly to clot toughness, with its effect increasing as fibrin content increases, because the reduced gel porosity at higher density results in greater expense of energy in fluid motion. Increasing fibrin content (1→10mg/mL) results in a significant increase in clot toughness (3→15 N/m) in accordance with a power law relation reminiscent of cellular solids and elastomeric gels. These results provide a basis for understanding and predicting the tendency for thrombotic embolization. STATEMENT OF SIGNIFICANCE: Fibrin, a naturally occurring biomaterial, is the major determinant of the structural and mechanical integrity of blood clots. We determined that increasing the fibrin content in clots, as in some thrombi and fibrin-based anti-bleeding sealants, results in an increase in clot toughness. Toughness corresponds to the ability to resist rupturing in the presence of a defect. We couple bulk mechanical testing, microstructural measurements, and finite element modeling to capture the force-stretch response of fibrin clots and compute toughness. We show that increased fibrin content in clots reduces porosity and limits fluid motion and that fluid motion drastically alters the clot toughness. These results provide a fundamental understanding of blood clot rupture and could help in rational design of fibrin-containing biomaterials.

Finite deformation near a crack tip terminated at an interface between two neo-Hookean sheets.

A crack terminating at an arbitrary angle to the interface between two neo-Hookean sheets is investigated under plane stress conditions using finite deformation theory. The asymptotic crack-tip deformation and stress fields are analyzed as a function of the ratio of the moduli and the angle of the crack relative to the interface. Full-held numerical calculations and experimental studies validate the analytical results. A stretch-based crack growth criterion is developed using crack-tip held solutions. Such criterion can predict the delay of crack growth through the bi-material interface observed in experiments and can be extended to any heterogeneity and material.

Rupture of blood clots: Mechanics and pathophysiology.

Fibrin is the three-dimensional mechanical scaffold of protective blood clots that stop bleeding and pathological thrombi that obstruct blood vessels. Fibrin must be mechanically tough to withstand rupture, after which life-threatening pieces (thrombotic emboli) are carried downstream by blood flow. Despite multiple studies on fibrin viscoelasticity, mechanisms of fibrin rupture remain unknown. Here, we examined mechanically and structurally the strain-driven rupture of human blood plasma-derived fibrin clots where clotting was triggered with tissue factor. Toughness, i.e., resistance to rupture, quantified by the critical energy release rate (a measure of the propensity for clot embolization) of physiologically relevant fibrin gels was determined to be 7.6 ± 0.45 J/m2. Finite element (FE) simulations using fibrin material models that account for forced protein unfolding independently supported this measured toughness and showed that breaking of fibers ahead the crack at a critical stretch is the mechanism of rupture of blood clots, including thrombotic embolization.

Tailoring and understanding the mechanical properties of nanoparticle-shelled bubbles.

One common approach to generate lightweight materials with high specific strength and stiffness is the incorporation of stiff hollow microparticles (also known as bubbles or microballoons) into a polymeric matrix. The mechanical properties of these composites, also known as syntactic foams, greatly depend on those of the hollow microparticles. It is critical to precisely control the properties of these bubbles to fabricate lightweight materials that are suitable for specific applications. In this paper, we present a method to tailor the mechanical properties and response of highly monodisperse nanoparticle-shelled bubbles using thermal treatment. We characterize the mechanical properties of individual as-assembled bubbles as well as those of thermally treated ones using nanoindentation and quantitative in situ compression tests. As-assembled bubbles display inelastic response, whereas thermally treated bubbles behave elastically. We also show that the stiffness and strength of bubbles are enhanced significantly, as much as 12 and 14 times that of the as-assembled bubbles, respectively, via thermal treatment. We complement the experimental results with finite element analysis (FEA) to understand the effect of shell thickness nonuniformity as well as the inelasticity on the mechanical response and fracture behavior of these bubbles. We demonstrate that the failure mechanism of bubbles incorporated into a polymer composite depends on the structure of the bubbles.