{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:25:47Z","timestamp":1786991147166,"version":"build-2736575974"},"reference-count":66,"publisher":"American Chemical Society (ACS)","issue":"13","license":[{"start":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T00:00:00Z","timestamp":1584921600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T00:00:00Z","timestamp":1584921600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T00:00:00Z","timestamp":1584921600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100005714","name":"Office of Experimental Program to Stimulate Competitive Research","doi-asserted-by":"publisher","award":["IIA-1355423"],"award-info":[{"award-number":["IIA-1355423"]}],"id":[{"id":"10.13039\/100005714","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State of South Dakota"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>One major limitation hindering the translation of in vitro osteoarthritis research into clinical disease-modifying therapies is that chondrocytes rapidly spread and dedifferentiate under standard monolayer conditions. Current strategies to maintain rounded morphologies of chondrocytes in culture either unnaturally restrict adhesion and place chondrocytes in an excessively stiff mechanical environment or are impractical for use in many applications. To address the limitations of current techniques, we have developed a unique composite thin-film cell culture platform, the CellWell, to model articular cartilage that utilizes micropatterned hemispheroidal wells, precisely sized to fit individual cells (12\u201318 \u03bcm diameters), to promote physiologically spheroidal chondrocyte morphologies while maintaining compatibility with standard cell culture and analytical techniques. CellWells were constructed of 15-\u03bcm-thick 5% agarose films embedded with electrospun poly\u00ad(vinyl alcohol) (PVA) nanofibers. Transmission electron microscope (TEM) images of PVA nanofibers revealed a mean diameter of 60.9 \u00b1 24 nm, closely matching the observed 53.8 \u00b1 29 nm mean diameter of human ankle collagen II fibers. Using AFM nanoindentation, CellWells were found to have compressive moduli of 158 \u00b1 0.60 kPa at 15 \u03bcm\/s indentation, closely matching published stiffness values of the native pericellular matrix. Primary human articular chondrocytes taken from ankle cartilage were seeded in CellWells and assessed at 24 h. Chondrocytes maintained their rounded morphology in CellWells (mean aspect ratio of 0.87 \u00b1 0.1 vs three-dimensional (3D) control [0.86 \u00b1 0.1]) more effectively than those seeded under standard conditions (0.65 \u00b1 0.3), with average viability of &amp;gt;85%. The CellWell\u2019s design, with open, hemispheroidal wells in a thin film substrate of physiological stiffness, combines the practical advantages of two-dimensional (2D) culture systems with the physiological advantages of 3D systems. Through its ease of use and ability to maintain the physiological morphology of chondrocytes, we expect that the CellWell will enhance the clinical translatability of future studies conducted using this culture platform.<\/jats:p>","DOI":"10.1021\/acsami.9b22596","type":"journal-article","created":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T13:49:30Z","timestamp":1584971370000},"page":"14814-14824","source":"Crossref","is-referenced-by-count":11,"title":["Micropatterned Biphasic Nanocomposite\nPlatform for Maintaining Chondrocyte Morphology"],"prefix":"10.1021","volume":"12","author":[{"given":"Ram","family":"Saraswat","sequence":"first","affiliation":[{"name":"South Dakota School of Mines & Technology , , 501 E St Joseph St , , ,","place":["Rapid City, South Dakota, United States, 57701"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishara","family":"Ratnayake","sequence":"additional","affiliation":[{"name":"South Dakota School of Mines & Technology , , 501 E St Joseph St , , ,","place":["Rapid City, South Dakota, United States, 57701"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Celeste","family":"Perez","sequence":"additional","affiliation":[{"name":"South Dakota School of Mines & Technology , , 501 E St Joseph St , , ,","place":["Rapid City, South Dakota, United States, 57701"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Schutz","sequence":"additional","affiliation":[{"name":"South Dakota School of Mines & Technology , , 501 E St Joseph St , , ,","place":["Rapid City, South Dakota, United States, 57701"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9311-2110","authenticated-orcid":true,"given":"Zhengtao","family":"Zhu","sequence":"additional","affiliation":[{"name":"South Dakota School of Mines & Technology , , 501 E St Joseph St , , ,","place":["Rapid City, South Dakota, United States, 57701"]},{"name":"South Dakota School of Mines & Technology , , 501 E St Joseph St , , ,","place":["Rapid City, South Dakota, United States, 57701"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Phillip","family":"Ahrenkiel","sequence":"additional","affiliation":[{"name":"South Dakota School of Mines & Technology , , 501 E St Joseph St , , ,","place":["Rapid City, South Dakota, United States, 57701"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6747-0547","authenticated-orcid":true,"given":"Scott T.","family":"Wood","sequence":"additional","affiliation":[{"name":"South Dakota School of Mines & Technology , , 501 E St Joseph St , , ,","place":["Rapid City, South Dakota, United States, 57701"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,3,23]]},"reference":[{"key":"2026081713151718900_cit1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/art.23176","article-title":"Estimates of the prevalence\nof arthritis and other rheumatic conditions in the United States.\nPart II","volume":"58","author":"Lawrence","year":"2008","journal-title":"Arthritis Rheum."},{"key":"2026081713151718900_cit2","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.knee.2016.01.017","article-title":"Correlation between histological\noutcome and surgical cartilage repair technique in the knee: A meta-analysis","volume":"23","author":"DiBartola","year":"2016","journal-title":"Knee"},{"key":"2026081713151718900_cit3","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1007\/s13346-015-0234-2","article-title":"Particle-based technologies for osteoarthritis\ndetection and therapy","volume":"6","author":"Kavanaugh","year":"2016","journal-title":"Drug Delivery Transl.\nRes."},{"key":"2026081713151718900_cit4","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.gene.2013.05.069","article-title":"A current review of molecular mechanisms regarding osteoarthritis\nand pain","volume":"527","author":"Lee","year":"2013","journal-title":"Gene"},{"key":"2026081713151718900_cit5","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1016\/s0140-6736(11)60243-2","article-title":"Osteoarthritis:\nan update with relevance for clinical practice","volume":"377","author":"Bijlsma","year":"2011","journal-title":"Lancet"},{"key":"2026081713151718900_cit6","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1056\/nejm199107113250203","article-title":"Comparison of an antiinflammatory\ndose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen\nin the treatment of patients with osteoarthritis of the knee","volume":"325","author":"Bradley","year":"1991","journal-title":"N. 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Bioeng."},{"key":"2026081713151718900_cit51","doi-asserted-by":"publisher","DOI":"10.1116\/1.4913565","article-title":"Restoration of chondrocytic phenotype on a two-dimensional\nmicropatterned surface","volume":"10","author":"Zhou","year":"2015","journal-title":"Biointerphases"},{"key":"2026081713151718900_cit52","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1177\/1087057117696795","article-title":"Three-Dimensional Cell Cultures in Drug Discovery and\nDevelopment","volume":"22","author":"Fang","year":"2017","journal-title":"SLAS Discovery"},{"key":"2026081713151718900_cit53","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1089\/ten.TEA.2012.0215","article-title":"Culture of primary bovine chondrocytes\non a continuously expanding surface inhibits dedifferentiation","volume":"18","author":"Rosenzweig","year":"2012","journal-title":"Tissue Eng., Part A"},{"key":"2026081713151718900_cit54","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1089\/ten.TEA.2010.0434","article-title":"Can microcarrier-expanded\nchondrocytes synthesize cartilaginous tissue in vitro?","volume":"17","author":"Surrao","year":"2011","journal-title":"Tissue Eng., Part A"},{"key":"2026081713151718900_cit55","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1002\/biot.201100017","article-title":"Chemically cross-linked chitosan hydrogel loaded with gelatin for\nchondrocyte encapsulation","volume":"6","author":"Hu","year":"2011","journal-title":"Biotechnol. 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