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In early osteoarthritis (OA), depletion of negatively charged glycosaminoglycans (GAGs) side chains within cartilage reduces its ability to maintain high osmotic pressure, leaving the matrix susceptible to further damage. In the biomechanical recovery of damaged cartilage, some OA therapies have focused on collagen repair to restore tissue stiffness, but comparatively fewer have targeted the osmotic contribution of GAGs to cartilage mechanics. In this study, we have investigated poly(styrene) sulfonate (PSS) as a synthetic proteoglycan mimic to restore lost negative charge in GAG\u2010depleted cartilage. Notably, PSS treatment led to near complete recovery of tissue permeability, a direct measure of fixed charge density. In contrast, other commercially available treatments tested did not show measurable biomechanical improvements. These findings, combined with tissue cytotoxicity experiments, demonstrate that PSS\u2010based molecules as synthetic GAG replacements are effective in restoring lost fixed charge density (FCD) and subsequent biomechanical properties of cartilage, thus supporting the potential of PSS as a novel therapeutic strategy for OA.<\/jats:p>","DOI":"10.1002\/jor.70177","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T01:23:51Z","timestamp":1773365031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dose\u2010Dependent, Biomechanical Recovery of Permeability Ex Vivo in GAG\u2010Depleted Cartilage With a Synthetic Polyelectrolyte, Polystyrene Sulfonate"],"prefix":"10.1002","volume":"44","author":[{"given":"Qurat\u2010Ul\u2010Ain","family":"Bhatti","sequence":"first","affiliation":[{"name":"Department of Materials Science and Engineering University of Delaware Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Sundar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Delaware Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Koopman","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering University of Delaware Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe A.","family":"Fields","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Delaware Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyla F.","family":"Ortved","sequence":"additional","affiliation":[{"name":"Department of Clinical Studies\u2010New Bolton Center University of Pennsylvania Kennett Square Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2687-7540","authenticated-orcid":false,"given":"David L.","family":"Burris","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Delaware Newark Delaware USA"},{"name":"Department of Mechanical Engineering University of Delaware Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-3741","authenticated-orcid":false,"given":"Justin","family":"Parreno","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Delaware Newark Delaware USA"},{"name":"Department of Biological Sciences University of Delaware Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure V.","family":"Kayser","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering University of Delaware Newark Delaware USA"},{"name":"Department of Chemistry and Biochemistry University of Delaware Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles B.","family":"Dhong","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering University of Delaware Newark Delaware USA"},{"name":"Department of Biomedical Engineering University of Delaware Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1941738109350438"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1249\/mss.0b013e31815cb1fc"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.2894880"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.26434\/chemrxiv-2025-b0pbp"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303737200"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1222470110"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.90B4.20284"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060719"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102080"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.4c00479"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2PY00271J"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-021-00328-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-11-231"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.4032917"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEC.2019.0116"},{"key":"e_1_2_8_17_1","unstructured":"S. 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