{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:54:59Z","timestamp":1791986099949,"version":"4.4.0"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T00:00:00Z","timestamp":1686355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000849","name":"NC3R- and British Heart Foundation co-funded PhD studentship","doi-asserted-by":"publisher","award":["NC\/R001642\/1"],"award-info":[{"award-number":["NC\/R001642\/1"]}],"id":[{"id":"10.13039\/501100000849","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/gels9060477","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T02:28:42Z","timestamp":1686536922000},"page":"477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Developing Biomimetic Hydrogels of the Arterial Wall as a Prothrombotic Substrate for In Vitro Human Thrombosis Models"],"prefix":"10.3390","volume":"9","author":[{"given":"Jacob","family":"Ranjbar","sequence":"first","affiliation":[{"name":"School of Medicine, Keele University, Keele ST5 5BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1365-5129","authenticated-orcid":false,"given":"Wanjiku","family":"Njoroge","sequence":"additional","affiliation":[{"name":"School of Pharmacy & Bioengineering, Keele University, Keele ST5 5BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0372-5352","authenticated-orcid":false,"given":"Jonathan M.","family":"Gibbins","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular and Metabolic Research, University of Reading, Reading RG6 6UB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4135-9733","authenticated-orcid":false,"given":"Paul","family":"Roach","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Science, Loughborough University, Loughborough LE11 3TU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1362-6040","authenticated-orcid":false,"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy & Bioengineering, Keele University, Keele ST5 5BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2413-4823","authenticated-orcid":false,"given":"Alan G. S.","family":"Harper","sequence":"additional","affiliation":[{"name":"School of Medicine, Keele University, Keele ST5 5BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.4103\/0019-5049.144643","article-title":"Overview of the coagulation system","volume":"58","author":"Palta","year":"2014","journal-title":"Indian J. Anaesth."},{"key":"ref_2","first-page":"170","article-title":"Mouse models of human disease: An evolutionary perspective","volume":"2016","author":"Perlman","year":"2016","journal-title":"Evol. Med. Public. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.thromres.2015.02.016","article-title":"Murine arterial thrombus induction mechanism influences subsequent thrombodynamics","volume":"135","author":"Cooley","year":"2015","journal-title":"Thromb. 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