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The inflammation often originates from the fibrocartilage region of the enthesis as a consequence of mechanical overuse or \u2010load and consequently tissue damage. During enthesitis, waves of inflammatory cytokines propagate in(to) the fibrocartilage, resulting in detrimental, heterotopic bone formation. Understanding of human enthesitis and its treatment options is limited, also because of lacking in vitro model systems that can closely mimic the pathophysiology of the enthesis and can be used to develop therapies. In this study, an enthes(it)is\u2010on\u2010chip model is developed. On opposite sides of a porous culture membrane separating the chip's two microfluidic compartments, human mesenchymal stromal cells are selectively differentiated into tenocytes and fibrochondrocytes. By introducing an inflammatory cytokine cocktail into the fibrochondrocyte compartment, key aspects of acute and chronic enthesitis, measured as increased expression of inflammatory markers, can be recapitulated. Upon inducing chronic inflammatory conditions, hydroxyapatite deposition, enhanced osteogenic marker expression and reduced secretion of tissue\u2010related extracellular matrix components are observed. Adding the anti\u2010inflammatory drug celecoxib to the fibrochondrocyte compartment mitigates the inflammatory state, demonstrating the potential of the enthesitis\u2010on\u2010chip model for drug testing.<\/jats:p>","DOI":"10.1002\/adhm.202401815","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T03:41:40Z","timestamp":1724730100000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Enthesitis on Chip \u2013 A Model for Studying Acute and Chronic Inflammation of the Enthesis and its Pharmacological Treatment"],"prefix":"10.1002","volume":"13","author":[{"given":"Francesca","family":"Giacomini","sequence":"first","affiliation":[{"name":"Department of Instructive Biomaterials Engineering MERLN Institute for Technology\u2010Inspired Regenerative Medicine Maastricht University  Universiteitssingel 40 Maastricht 6229 ER The 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