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However, current animal models have limitations in replicating cold\u2010induced acral injury due to their low sensitivity to cold. Moreover, existing in vitro vascular chips composed of endothelial cells and perfusion systems lack temperature responsiveness, failing to simulate the vasoconstriction observed under cold stress. This study presents a novel approach where a microfluidic bioreactor of vessel\u2010on\u2010a\u2010chip was developed by grafting the inner microchannel surface of polydimethylsiloxane with a thermosensitive hydrogel skin composed of <jats:italic>N<\/jats:italic>\u2010isopropyl acrylamide and gelatin methacrylamide. With a lower critical solution temperature\u00a0set at 30\u00b0C, the gel layer exhibited swelling at low temperatures, reducing the flow rate inside the channel by 10% when the temperature dropped from 37\u00b0C to 4\u00b0C. This well mimicked the blood stasis observed in capillary vessels in vivo. The vessel\u2010on\u2010a\u2010chip was further constructed by culturing endothelial cells on the surface of the thermosensitive hydrogel layer, and a perfused medium was introduced to the cells to provide a physiological shear stress. Notably, cold stimulation of the vessel\u2010on\u2010a\u2010chip led to cell necrosis, mitochondrial membrane potential (\u0394<jats:italic>\u03a8<\/jats:italic><jats:sub>m<\/jats:sub>) collapse, cytoskeleton disaggregation, and increased levels of reactive oxygen species. In contrast, the static culture of endothelial cells showed limited response to cold exposure. By faithfully replicating cold\u2010induced endothelial injury, this groundbreaking thermosensitive vessel\u2010on\u2010a\u2010chip technology offers promising advancements in the study of cold\u2010induced cardiovascular diseases, including pathogenesis and therapeutic drug screening.<\/jats:p>","DOI":"10.1002\/bit.28779","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T05:25:28Z","timestamp":1719811528000},"page":"3239-3251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Temperature\u2010responsive hydrogel\u2010grafted vessel\u2010on\u2010a\u2010chip: Exploring cold\u2010induced endothelial injury"],"prefix":"10.1002","volume":"121","author":[{"given":"Chong","family":"Shen","sequence":"first","affiliation":[{"name":"Key Laboratory of Smart Biomaterials of Zhejiang Province, College of Chemical and Biological Engineering Zhejiang University Hangzhou China"},{"name":"Center 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