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Herein, we report the use of a dynamically crosslinked hydrazone-based zwitterionic hydrogel based on mixing hydrazide (ZH) and aldehyde (ZA) or ketone (ZK)-functionalized precursor polymers as an alternative to hyaluronic acid-based viscosupplements. Upon coinjection via a double-barrel syringe, the water-like precursor polymer solutions gel within \u223c0.5\u20133 min. Relative to a leading hyaluronic acid-based product (Synvisc\u00ae), the dynamic zwitterionic hydrogels showed 10\u201350\u00d7 higher compressive moduli, beneficial to mechanically support the joint while at the same time exhibiting a 5\u20139\u00d7 higher reduction in the coefficient of friction at walking frequencies against an alumina surface over 400 cycles and a &amp;gt;25% lower coefficient of friction against ex vivo cartilage samples, all while also being easy to inject given the low initial viscosity of the precursor polymers. The hydrogel was noncytotoxic and showed minimal inflammatory responses when injected in vivo, with the ZA formulations persisting for &amp;gt;90 days postinjection compared to only days for conventional HA-based viscosupplements. Overall, zwitterionic dynamic hydrogels provide a combination of mechanical support, lubricity, and in vivo inertness\/stability while being injectable, suggesting promise for clinical translation for osteoarthritis treatment.<\/jats:p>","DOI":"10.1021\/acsami.6c15705","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:01:36Z","timestamp":1789448496000},"page":"50647-50662","source":"Crossref","is-referenced-by-count":0,"title":["Injectable Dynamically Crosslinked Zwitterionic Hydrogels as a Viscosupplement for Osteoarthritis Treatment"],"prefix":"10.1021","volume":"18","author":[{"given":"Nahieli Preciado","family":"Rivera","sequence":"first","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Jenkins","sequence":"additional","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duy Anh","family":"Pham","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Montr\u00e9al , , 2940 Chemin de Polytechnique , , ,","place":["Montr\u00e9al, QC, Canada, H3T 1J4"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma A.","family":"Garza Flores","sequence":"additional","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"McCabe","sequence":"additional","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj","family":"Saini","sequence":"additional","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurpreet K.","family":"Randhawa","sequence":"additional","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandana","family":"Tavakolian","sequence":"additional","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saanvi","family":"Sood","sequence":"additional","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Belchos","sequence":"additional","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Jun","sequence":"additional","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3342-3179","authenticated-orcid":true,"given":"Xavier","family":"Banquy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Montr\u00e9al , , 2940 Chemin de Polytechnique , , ,","place":["Montr\u00e9al, QC, Canada, H3T 1J4"]},{"name":"Universit\u00e9 de Montr\u00e9al , , 2940 Chemin de Polytechnique , , ,","place":["Montr\u00e9al, QC, Canada, H3T 1J4"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5698-8463","authenticated-orcid":true,"given":"Todd","family":"Hoare","sequence":"additional","affiliation":[{"name":"McMaster University , , 1280 Main St. W. , , ,","place":["Hamilton, ON, Canada, L8S 4L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"2026100820083749300_cit1","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1097\/01.blo.0000143938.30681.9d","article-title":"The Impact of Osteoarthritis: Implications for Research","volume":"427","author":"Buckwalter","year":"2004","journal-title":"Clin. 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