Developing biomimetic hydrogels of the arterial wall as a prothrombotic substrate for in vitro human thrombosis models

Ranjbar, J., Njoroge, W. ORCID: https://orcid.org/0009-0003-1365-5129, Gibbins, J. M. ORCID: https://orcid.org/0000-0002-0372-5352, Roach, P. ORCID: https://orcid.org/0000-0003-4135-9733, Yang, Y. ORCID: https://orcid.org/0000-0002-1362-6040 and Harper, A. G. S. ORCID: https://orcid.org/0000-0003-2413-4823 (2023) Developing biomimetic hydrogels of the arterial wall as a prothrombotic substrate for in vitro human thrombosis models. Gels, 9 (6). 477. ISSN 2310-2861 doi: 10.3390/gels9060477

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/112337
Identification Number/DOI	10.3390/gels9060477
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Uncontrolled Keywords	Polymers and Plastics, Organic Chemistry, Biomaterials, Bioengineering
Publisher	MDPI AG
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