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Developing a Biomimetic 3D Neointimal Layer as a Prothrombotic Substrate for a Humanized In Vitro Model of
Jassim Echrish1, Madalina-Ioana Pasca1, David Cabrera2
1School of Medicine, Keele University, Keele ST5 5BG, UK.
Biomimetics (Basel, Switzerland)
|June 26, 2024
Summary
Researchers developed a biomimetic hydrogel mimicking atherosclerotic plaque
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Biomedical Engineering
Background:
- Acute cardiovascular events stem from blood clots forming on ruptured or eroded atherosclerotic plaques.
- Understanding plaque thrombogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To create a functional biomimetic hydrogel of the atherosclerotic plaque's neointimal layer.
- To investigate the hydrogel's ability to support blood clot formation (thrombogenesis) upon exposure to human blood.
Main Methods:
- THP-1-derived foam cells were cultured within 3D collagen hydrogels, with and without atorvastatin.
- Foam cell formation was induced using oxidized low-density lipoprotein (LDL).
- Prothrombin time, platelet aggregation, and extrinsic coagulation pathway activity were measured after exposing the hydrogel to human blood components.
Main Results:
- The biomimetic hydrogel successfully induced platelet aggregation and blood coagulation when exposed to human blood products.
- Foam cell formation was observed, and atorvastatin pretreatment inhibited this process.
- Atorvastatin significantly reduced the hydrogel's pro-aggregatory and pro-coagulant effects.
Conclusions:
- A functional 3D neointimal biomimetic hydrogel was successfully produced.
- This hydrogel can serve as a platform for studying atherosclerosis development and screening anti-thrombotic drugs.
- The model offers a potential alternative to animal models for thrombosis research.
