Tissue-engineered collagenous fibrous cap models to systematically elucidate atherosclerotic plaque rupture

Area of Science:

• Biomaterials science
• Cardiovascular research
• Tissue engineering

Background:

• Vascular thrombotic events often result from atherosclerotic plaque fibrous cap rupture.
• Predicting cap rupture is challenging due to plaque heterogeneity, unknown material properties, and event stochasticity.

Purpose of the Study:

• To develop tissue-engineered human fibrous cap models with controllable collagen composition.
• To enable mechanical testing and scrutinize the relationship between composition and mechanical properties.

Main Methods:

• Myofibroblasts were cultured in fibrin-based gels for 21 days under dynamic culture conditions (static, intermittent, or continuous loading).
• A soft fibrin inclusion was introduced to mimic the lipid core, creating heterogeneous tissue models.
• Collagen composition (amount, type, organization) was varied by culture protocol and inclusion.

Main Results:

• Reproducible collagenous tissues mimicking human fibrous cap mechanical properties were generated.
• The models exhibited varied collagen composition influenced by the soft inclusion and culture method.
• Successful integration of the soft core demonstrated the model's ability to simulate plaque heterogeneity.

Conclusions:

• The developed tissue-engineered models accurately replicate human fibrous cap mechanics and composition.
• These models are suitable for investigating tissue mechanics, evolution, and failure in fibrous caps.
• The models can be applied to study the failure of complex, heterogeneous tissues in general.