- The paper presents a validated simulation framework integrating Navier-Stokes and convection-diffusion-reaction equations to investigate thrombus dynamics in micro-crevices.
- The study finds that high shear rates significantly increase clot volume in narrow crevices while effective surface coatings like MPC reduce platelet deposition.
- The research underscores that both flow conditions and surface reactivity critically influence thrombogenesis, advocating for targeted hemocompatible designs in device engineering.
Background and Motivation
Device-induced thrombogenesis remains a critical challenge in mechanical circulatory support (MCS) systems, particularly with ventricular assist devices (VADs), where adverse thromboembolic events, such as pump thrombosis and stroke, are significant contributors to morbidity and mortality. Complex device geometries, including internal steps and micro-crevices necessitated by modular design and assembly, constitute principal sites for thrombus formation. In these regions, local hemodynamics and biomaterial properties crucially modulate the equilibrium between platelet deposition and removal, dictating thrombotic risk. The present study delivers a multi-constituent continuum thrombosis simulation, rigorously validated against microfluidic experiment, to probe the interplay between wall shear rate and surface reactivity on thrombus dynamics within micro-crevice geometries.
Mathematical and Computational Approach
A multi-constituent thrombosis framework combining Navier-Stokes equations for Newtonian blood flow with convection-diffusion-reaction (CDR) equations for platelet and biochemical species transport underlies the analysis. The model resolves the coupled dynamics of fluid phase (RBCs and plasma) and a deposited platelet phase (thrombus), incorporating a drag-interaction term to capture the hemodynamic resistance posed by growing thrombi. Platelet kinetics—comprising activation (biochemical and shear-induced), deposition, aggregation, stabilization, erosion (shear-cleaning), and inhibition—are modeled via state-specific CDR equations with explicit surface boundary reactions parameterized for biomaterial properties.
The computational domain replicates the experimental microfluidic channel with a PDMS channel and Ti6Al4V, collagen-coated, or MPC-coated Ti6Al4V substrates. Simulations leverage OpenFOAM v6 on a 3D mesh (up to 600,000 cells) at physiologically relevant wall shear rates (400 and 1000 s⁻¹). Platelet inflow boundary conditions replicate experimental hematological parameters, and all parameter values are consistent with prior validated models.
Key Numerical Results
Shear Rate Effects:
- Across all crevice sizes, thrombus formation was localized to the top corners due to the flow-induced stagnation regions, mapping precisely to areas of near-zero wall shear.
- High wall shear rate (1000 s⁻¹) increased thrombus volume within the crevice compared to low shear (400 s⁻¹), but concomitantly reduced deposition outside the crevice due to increased "shear cleaning".
- In narrow crevices (53 μm and 90 μm width), the effect of increased shear rate on clot volume was pronounced (106% and 97% increase, respectively), while the widest crevice (137 μm) showed only a 19% increase, reflecting efficient washout and sub-threshold activation due to less agonist accumulation.
Surface Chemistry Effects:
- Platelet deposition was highly sensitive to boundary reaction rates: collagen led to extensive, contiguous thrombus formation both inside and outside the crevice, while MPC-Ti6Al4V nearly eliminated deposition, confining small clots only to regions of pronounced stagnation.
- Activated platelet boundary deposition rates spanned an order of magnitude across materials, determining the degree of thrombosis independently of crevice geometry within the simulation timescale.
- The fidelity between simulation and experimental patterning strengthens the assertion that surface chemistry is as critical as flow rate in device thrombogenicity.
Combined Geometric and Biochemical Impacts:
- Narrow, deep crevices promote agonist entrapment and exponential platelet activation via recirculation zones, leading to localized, persistent thrombus—a finding consistent with clinical explant observations.
- Deposition patterns, especially the vertical extension of clots at crevice corners, are controlled by three-dimensional secondary flows, including vortex-driven impingement.
Theoretical and Practical Implications
The numerical data robustly validate that low-shear, recirculating microenvironments and highly reactive biomaterial surfaces synergistically drive device-associated thrombogenesis. The results challenge traditional approaches that consider only macroscopic shear or gross surface properties and underscore the necessity for integrated design strategies. Specifically, increasing bulk flow may paradoxically exacerbate thrombus risk within low-shear crevices while attenuating it on high-washout surfaces. Thus, device design should favor flow conditions and geometries that minimize stagnant recirculation and utilize locally applied, high-hemocompatibility coatings in regions where crevices are unavoidable.
The study advocates for a targeted engineering approach: application of biocompatible coatings like MPC polymers precisely within identified low-shear zones, coupled with optimal crevice aspect ratios to avoid agonist accumulation and promote convective clearance.
Limitations and Future Directions
Model limitations include the exclusion of sidewall reactivity, absence of explicit RBC-mediated margination phenomena, and the constraint to low-Reynolds-number regimes, which may not fully capture conditions in macroscopic devices. Furthermore, stochastic and deformational aspects of individual platelet transport, as well as vWF mediated mechanochemistry, are not explicitly modeled. The extension of this framework to incorporate multiphase transport (to account for RBC trafficking), phase-field/particle-based interface models, and shear accumulator history for platelet activation will enhance predictive fidelity. Ongoing work aims to adapt and validate this model in actual VAD geometries with full biomaterial and flow heterogeneity, particularly addressing vWF phenomena in high-shear zones and performing global sensitivity analyses to dissect parameter contributions.
Conclusion
This study provides a quantitative, validated computational model delineating the relative contributions of shear rate and surface chemistry in the regulation of thrombus formation within micro-crevice geometries relevant to MCS device design. The results demonstrate that (i) micro-crevices with low-shear, recirculating flow, (ii) geometries supporting agonist entrapment, and (iii) high-reactivity surfaces are principal determinants of localized thrombosis. The research suggests that holistic device design incorporating rational geometry, tailored surface chemistry, and flow field optimization is indispensable for mitigating thromboembolic risk in blood-contacting medical devices.
Reference: "Influence of shear rate and surface chemistry on thrombus formation in micro-crevice" (2011.10560)
