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While marine-derived chitosan offers sustainable antioxidative potential, its poor solubility limits clinical use. In this study, we developed an injectable, thermoresponsive hydroxybutyl chitosan (HBC) hydrogel that combines intrinsic radical-scavenging activity with thermoresponsive modulation of the local hydrated microenvironment. HBC (degree of substitution: 1.88; Mw: 188 \u00b1 34 kDa) demonstrated robust radical scavenging, reaching 80% for hydroxyl radicals at a concentration of 1.6 mg\/mL. At 37 \u00b0C, HBC exhibited rapid, concentration-dependent gelation (40\u201360 s), forming hydrogels that exhibited time- and concentration-dependent increases in modulus and a characteristic 40% diameter shrinkage. HBC hydrogel extracts were not cytotoxic, maintaining metabolic activity levels near the positive controls for both L929 fibroblasts and human dermal fibroblasts (HDFs). In a hydrogen peroxide-induced senescence model using HDFs, the 5% HBC hydrogel led to a significant decrease in senescence-associated beta-galactosidase activity (&amp;gt;50%) and mitigated intracellular reactive oxygen species activity. Furthermore, HBC treatment effectively sustained collagen I synthesis. These findings support marine-derived HBC as a multifunctional, thermoresponsive biomaterial with potential for skin-regenerative and anti-aging applications involving oxidative stress modulation.<\/jats:p>","DOI":"10.1021\/acsabm.6c01206","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:02:28Z","timestamp":1792497748000},"page":"10232-10249","source":"Crossref","is-referenced-by-count":0,"title":["Marine-Derived Injectable Hydroxybutyl Chitosan with Tunable Thermoresponsive Properties and Potential Anti-aging Applications"],"prefix":"10.1021","volume":"9","author":[{"given":"Shuanglan","family":"Du","sequence":"first","affiliation":[{"name":"IMDEA Materials Institute , , ,","place":["Getafe, Madrid, Spain, 28906"]},{"name":"Universidad Polit\u00e9cnica de Madrid , , ,","place":["Madrid, Madrid, Spain, 28040"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Navarrete-Segado","sequence":"additional","affiliation":[{"name":"IMDEA Materials Institute , , ,","place":["Getafe, Madrid, Spain, 28906"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoriia","family":"Sevostianova","sequence":"additional","affiliation":[{"name":"IMDEA Materials Institute , , ,","place":["Getafe, Madrid, Spain, 28906"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6927-6548","authenticated-orcid":true,"given":"Jennifer","family":"Patterson","sequence":"additional","affiliation":[{"name":"IMDEA Materials Institute , , ,","place":["Getafe, Madrid, Spain, 28906"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"issue":"1","key":"2026110201081814300_cit1","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s13287-021-02262-4","article-title":"Chitosan Hydrogel-Loaded MSC-Derived Extracellular Vesicles Promote Skin Rejuvenation by Ameliorating the Senescence of Dermal Fibroblasts","volume":"12","author":"Zhao","year":"2021","journal-title":"Stem Cell Res. 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