A versatile hybrid agent-based, particle and partial differential equations method to analyze vascular adaptation.

Area of Science:

• Biomedical Engineering
• Computational Biology
• Vascular Biology

Background:

• Peripheral arterial occlusive disease affects millions, with interventions like vein graft bypasses often failing.
• Intervention failure stems from intricate interactions between vascular biology, biomechanics, and clinical decisions.
• Understanding graft adaptation is crucial for improving endovascular treatment success rates.

Purpose of the Study:

• To develop a versatile computational model simulating the feedback loop between cellular/tissue events and mechano-environmental conditions in vein graft adaptation.
• To improve upon previous agent-based models by incorporating more realistic biological laws and the role of vein membranes.
• To offer a modular hybrid approach combining agent-based modeling, continuum mechanics, and particle-tracking for multiscale phenomena.

Main Methods:

• A hybrid computational model integrating agent-based principles, continuum mechanics, and particle-tracking methods.
• Utilized an immersed boundary implementation of viscous flow to model smooth muscle cell (SMC) motility and matrix reorganization.
• Focused on a modular design allowing adjustable complexity and physiological realism for simulating graft adaptation.

Main Results:

• The model captures the interplay between intimal hyperplasia and wall remodeling, key determinants of vein graft success or failure.
• Simulations demonstrated that mechanical homeostasis drives cellular motility and extracellular matrix balance, crucial for accurate histological distribution.
• The hybrid model facilitates rapid hypothesis testing for factors influencing graft adaptation, particularly cellular behavior.

Conclusions:

• A novel modular hybrid computational model effectively simulates the multiscale adaptation phenomena in peripheral endovascular interventions.
• The model highlights the critical role of mechanical homeostasis in regulating cellular behavior and extracellular matrix organization for successful graft adaptation.
• This approach offers a powerful tool for investigating and potentially improving outcomes in treatments for peripheral arterial occlusive disease.