From Tissue to Simulation: A Review of Venous Valve Biomechanics, Extracellular Matrix Architecture, and Constitutive Modeling in Chronic Venous Insufficiency.

Chronic venous insufficiency (CVI) affects an estimated 25-40% of the adult population worldwide, yet the tissue-level mechanics driving venous valve failure remain largely uncharacterized. This review synthesizes experimental and computational literature on venous valve biomechanics as an integrated pipeline spanning biaxial mechanical testing, extracellular matrix (ECM) microstructural characterization, constitutive model development, and fluid-structure interaction (FSI) simulation. Our primary experimental source is biaxial data from bovine jugular and saphenous venous tissues, representing the only systematically characterized nonlinear anisotropic material parameters for venous tissue published to date. We situate those measurements within the broader landscape of soft-tissue constitutive modeling, tracing how model selection shapes both parameter identifiability and predictive reach. The ECM architecture of venous valve leaflets is not incidental background. Collagen crimp geometry, fiber orientation, and the parietal-to-luminal elastin gradient each leave distinct mechanical signatures in biaxial loading curves, and any constitutive model that ignores this structure cannot generalize reliably across loading states. Three unresolved gaps emerge from this synthesis: an off-axis circumferential prediction error in current exponential models, the absence of a failure criterion or damage evolution law for venous tissue under cyclic loading, and the lack of validated material parameters for bioprosthetic candidate materials. Each gap directly constrains the fidelity of FSI simulations coupling leaflet deformation to hemodynamic loading. We close by outlining the experimental and modeling steps required to close them, with particular emphasis on what the field needs before patient-specific simulation becomes clinically defensible.