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Developing a Biomimetic 3D Neointimal Layer as a Prothrombotic Substrate for a Humanized In Vitro Model of Atherothrombosis

Echrish, Jassim; Pasca, Madalina-Ioana; Cabrera, David; Yang, Ying; Harper, Alan G S


Jassim Echrish

Madalina-Ioana Pasca


Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel of the neointimal layer of the atherosclerotic plaque that can support thrombogenesis upon exposure to human blood. A biomimetic hydrogel of the neointima was produced by culturing THP-1-derived foam cells within 3D collagen hydrogels in the presence or absence of atorvastatin. Prothrombin time and platelet aggregation onset were measured after exposure of the neointimal models to platelet-poor plasma and washed platelet suspensions prepared from blood of healthy, medication-free volunteers. Activity of the extrinsic coagulation pathway was measured using the fluorogenic substrate SN-17. Foam cell formation was observed following preincubation of the neointimal biomimetic hydrogels with oxidized LDL, and this was inhibited by pretreatment with atorvastatin. The neointimal biomimetic hydrogel was able to trigger platelet aggregation and blood coagulation upon exposure to human blood products. Atorvastatin pretreatment of the neointimal biomimetic layer significantly reduced its pro-aggregatory and pro-coagulant properties. In the future, this 3D neointimal biomimetic hydrogel can be incorporated as an additional layer within our current thrombus-on-a-chip model to permit the study of atherosclerosis development and the screening of anti-thrombotic drugs as an alternative to current animal models.


Echrish, J., Pasca, M.-I., Cabrera, D., Yang, Y., & Harper, A. G. S. (2024). Developing a Biomimetic 3D Neointimal Layer as a Prothrombotic Substrate for a Humanized In Vitro Model of Atherothrombosis. Biomimetics, 9(6), Article 372.

Journal Article Type Article
Acceptance Date Jun 14, 2024
Online Publication Date Jun 20, 2024
Publication Date Jun 20, 2024
Deposit Date Jun 24, 2024
Journal Biomimetics
Print ISSN 2313-7673
Electronic ISSN 2313-7673
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 9
Issue 6
Article Number 372
Keywords atherosclerosis; biomimetic hydrogel; animal use alternatives; vascular tissue engineering; thrombosis; platelets; coagulation
Public URL
Publisher URL
PMID 38921252