Modeling thrombosis in silico: Frontiers, challenges, unresolved problems and milestones.

Area of Science:

• Biophysics
• Computational Biology
• Physiology

Background:

• Hemostasis maintains vascular integrity via platelets and coagulation, forming a hemostatic plug.
• Disorders of hemostasis, including bleeding and thrombosis, are major causes of mortality.
• Complex regulation involves cell mechanics, fluid dynamics, signaling, and network interactions.

Purpose of the Study:

• Review state-of-the-art computational modeling methods for thrombosis.
• Analyze unresolved challenges in modeling hemostasis and thrombosis.
• Highlight fundamental understanding and future prospects in the field.

Main Methods:

• Review of computational modeling techniques for thrombosis.
• Analysis of classical and innovative computational approaches.
• Discussion of coarse-graining, continuum vs. particle-based, multiscale, and hybrid models.

Main Results:

• Identified key challenges: physics of platelet aggregates/fibrin gels, computational limitations, biological unknowns, and spatiotemporal regulation complexities.
• Considered various modeling approaches including coarse-graining and multiscale methods.
• Highlighted fundamental insights gained from theoretical models.

Conclusions:

• Computational modeling is crucial for understanding complex hemostasis and thrombosis.
• Addressing identified challenges will advance predictive capabilities.
• Future research should focus on integrating multiscale models and parameter estimation for improved accuracy.