{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:14:30Z","timestamp":1789535670757,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T00:00:00Z","timestamp":1646438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1AR073964"],"award-info":[{"award-number":["RO1AR073964"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CAREER 1753352"],"award-info":[{"award-number":["CAREER 1753352"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CAREER 1554708"],"award-info":[{"award-number":["CAREER 1554708"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Articular cartilage is comprised of two main components, the extracellular matrix (ECM) and the pericellular matrix (PCM). The PCM helps to protect chondrocytes in the cartilage from mechanical loads, but in patients with osteoarthritis, the PCM is weakened, resulting in increased chondrocyte stress. As chondrocytes are responsible for matrix synthesis and maintenance, it is important to understand how mechanical loads affect the cellular responses of chondrocytes. Many studies have examined chondrocyte responses to in vitro mechanical loading by embedding chondrocytes in 3-D hydrogels. However, these experiments are mostly performed in the absence of PCM, which may obscure important responses to mechanotransduction. Here, drop-based microfluidics is used to culture single chondrocytes in alginate microgels for cell-directed PCM synthesis that closely mimics the in vivo microenvironment. Chondrocytes formed PCM over 10 days in these single-cell 3-D microenvironments. Mechanotransduction studies were performed, in which single-cell microgels mimicking the cartilage PCM were embedded in high-stiffness agarose. After physiological dynamic compression in a custom-built bioreactor, microgels exhibited distinct metabolomic profiles from both uncompressed and monolayer controls. These results demonstrate the potential of single cell encapsulation in alginate microgels to advance cartilage tissue engineering and basic chondrocyte mechanobiology.<\/jats:p>","DOI":"10.3390\/cells11050900","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:35:50Z","timestamp":1646598950000},"page":"900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate Microgels"],"prefix":"10.3390","volume":"11","author":[{"given":"Jacob P.","family":"Fredrikson","sequence":"first","affiliation":[{"name":"Department of Chemical & Biological Engineering, Montana State University, P.O. Box 173920, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka P.","family":"Brahmachary","sequence":"additional","affiliation":[{"name":"Department of Mechanical & Industrial Engineering, Montana State University, P.O. Box 173800, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayten E.","family":"Erdo\u011fan","sequence":"additional","affiliation":[{"name":"Department of Chemical & Biological Engineering, Montana State University, P.O. Box 173920, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary K.","family":"Archambault","sequence":"additional","affiliation":[{"name":"Department of Mechanical & Industrial Engineering, Montana State University, P.O. Box 173800, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James N.","family":"Wilking","sequence":"additional","affiliation":[{"name":"Department of Chemical & Biological Engineering, Montana State University, P.O. Box 173920, Bozeman, MT 59717, USA"},{"name":"Center for Biofilm Engineering, Montana State University, P.O. Box 173980, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-4109","authenticated-orcid":false,"given":"Ronald K.","family":"June","sequence":"additional","affiliation":[{"name":"Department of Mechanical & Industrial Engineering, Montana State University, P.O. Box 173800, Bozeman, MT 59717, USA"},{"name":"Department of Microbiology & Cell Biology, Montana State University, P.O. Box 173520, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-8223","authenticated-orcid":false,"given":"Connie B.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Chemical & Biological Engineering, Montana State University, P.O. Box 173920, Bozeman, MT 59717, USA"},{"name":"Center for Biofilm Engineering, Montana State University, P.O. Box 173980, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1136\/annrheumdis-2019-216515","article-title":"Global, regional and national burden of osteoarthritis 1990\u20132017: A systematic analysis of the Global Burden of Disease Study 2017","volume":"79","author":"Safiri","year":"2020","journal-title":"Ann. Rheum. 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