Microstructure-dependent transport properties in blood clots: Roles of fiber volume fraction and orientation on permeability and diffusivity

Fibrin networks serve as the fundamental structural framework of blood clots. The microstructural features of the networks govern the fluid and mass transport processes within blood clots, which are critical to thrombolytic therapy efficacy. However, quantitatively linking microstructure to macroscopic transport properties remains challenging due to structural complexity, e.g., high randomness of fiber orientation (θ, φ) and volume fraction (ϕ_f). To this end, we established a numerical framework combining representative volume element (RVE) and computational fluid dynamics to derive dimensionless hydraulic permeability (k*) and hindered diffusion coefficient (D*). In contrast to conventional models, we introduced θ and φ to capture orientation effects, further developing the ϕ_f-(θ,φ)-k^* and ϕ_f-(θ,φ)-D^* relationships through systematic simulations on 215 RVEs with varying θ, φ, and ϕ_f. The capacity of the proposed formulas for predicting transport properties in heterogeneous and anisotropic blood clots was tested and validated via in vitro, coronary artery, and aortic aneurysm clots. Moreover, we incorporated the established formulas into a multiscale and multiphysics fibrinolysis model to demonstrate how fibrin network structure influences fibrinolysis via affecting macroscopic fluid and mass transport. Results showed that k* exhibited a strong orientation dependency, whereas D* was orientation-insensitive. Additionally, orientation-dependent features were found in fibrinolysis patterns. Specifically, flow-parallel fibers (0°) guided permeating flow, enabling convective penetration and rapid core dissolution, whereas perpendicular (90°) structures disrupted direct pathways, resulting in slow, superficial erosion. The formulas proposed here enable a structure-informed framework for dynamically predicting local transport properties in realistic blood clots, aiding in pre-interventional assessment of thrombolytic therapy efficacy. STATEMENT OF SIGNIFICANCE: Blood clots exhibit pronounced structural heterogeneity and anisotropy, making it challenging to quantitatively link fibrin microstructure to macroscopic transport properties that govern thrombolytic efficacy. Here, we established a validated mathematical framework that explicitly incorporated fiber orientation distribution and volume fraction to predict macroscopic hydraulic permeability and hindered diffusion coefficients. By incorporating the proposed relationships into a multiscale fibrinolysis model, we directly connect fibrin architecture to lytic outcomes through its control of transport pathways. This framework enables structure-informed inference of local transport properties in realistic blood clots, aiding in pre-interventional assessment of thrombolytic therapy efficacy. The proposed relationships are general and readily extendable to other fibrous biological and engineered materials.