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Developing Biomimetic Hydrogels of the Arterial Wall as a Prothrombotic Substrate for In Vitro Human Thrombosis Models

Ranjbar, Jacob; Njoroge, Wanjiku; Gibbins, Jonathan M.; Roach, Paul; Yang, Ying; Harper, Alan G. S.

Authors

Jacob Ranjbar

Wanjiku Njoroge

Jonathan M. Gibbins

Paul Roach



Abstract

Current in vitro thrombosis models utilise simplistic 2D surfaces coated with purified components of the subendothelial matrix. The lack of a realistic humanised model has led to greater study of thrombus formation in in vivo tests in animals. Here we aimed to develop 3D hydrogel-based replicas of the medial and adventitial layers of the human artery to produce a surface that can optimally support thrombus formation under physiological flow conditions. These tissue-engineered medial- (TEML) and adventitial-layer (TEAL) hydrogels were developed by culturing human coronary artery smooth muscle cells and human aortic adventitial fibroblasts within collagen hydrogels, both individually and in co-culture. Platelet aggregation upon these hydrogels was studied using a custom-made parallel flow chamber. When cultured in the presence of ascorbic acid, the medial-layer hydrogels were able to produce sufficient neo-collagen to support effective platelet aggregation under arterial flow conditions. Both TEML and TEAL hydrogels possessed measurable tissue factor activity and could trigger coagulation of platelet-poor plasma in a factor VII-dependent manner. Biomimetic hydrogel replicas of the subendothelial layers of the human artery are effective substrates for a humanised in vitro thrombosis model that could reduce animal experimentation by replacing current in vivo models.

Citation

Ranjbar, J., Njoroge, W., Gibbins, J. M., Roach, P., Yang, Y., & Harper, A. G. S. (2023). Developing Biomimetic Hydrogels of the Arterial Wall as a Prothrombotic Substrate for In Vitro Human Thrombosis Models. Gels, 9(6), Article 477. https://doi.org/10.3390/gels9060477

Journal Article Type Article
Acceptance Date Jun 2, 2023
Online Publication Date Jun 10, 2023
Publication Date Jun 10, 2023
Deposit Date Jun 12, 2023
Journal Gels
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 9
Issue 6
Article Number 477
DOI https://doi.org/10.3390/gels9060477
Keywords Polymers and Plastics, Organic Chemistry, Biomaterials, Bioengineering
Public URL https://keele-repository.worktribe.com/output/444572