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Here, we report a bioactive injectable self\u2010healing hydrogel (COPRP) constructed by crosslinking oxidized\n                    <jats:italic>Polygonati rhizoma<\/jats:italic>\n                    polysaccharide (OPRP) with carboxymethyl chitosan via dynamic Schiff base linkages. OPRP is structurally identified as an inulin neoseries\u2010type fructan with relevance to TGF\u2010\u03b2\/Smad pathway regulation. Without levodopa loading, COPRP reduced ROS accumulation and M1\u2010associated inflammatory markers in LPS\u2010stimulated microglia. It also improved cell viability, preserved mitochondrial membrane potential, and maintained TH expression in 6\u2010OHDA\u2010challenged SH\u2010SY5Y cells, supporting the intrinsic bioactivity of the hydrogel matrix. In a 6\u2010OHDA rat PD model, COPRP significantly ameliorated motor deficits and preserved TH\u2010positive neurons. Incorporating levodopa into COPRP creates a dual\u2010mechanism platform combining active microenvironmental remodeling with passive dopaminergic supplementation. Proteomic analysis, corroborated by western blotting, identified the TGF\u2010\u03b2\/Smad signaling axis as the principal mechanistic mediator. Pharmacological intervention with pirfenidone attenuated TGF\u2010\u03b22\/Smad2\/3 activation and partially reduced the behavioral and neuroprotective effects associated with COPRP, supporting the functional involvement of this pathway. This work delineates how a defined polysaccharide structure modulates the intracranial pathological microenvironment, offering insights for the rational design of bioactive biomaterials targeting neurodegenerative disease.\n                  <\/jats:p>","DOI":"10.1002\/advs.77842","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:59:46Z","timestamp":1790801986000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of the TGF\u2010\u03b2\/Smad Signaling Pathway by a Bioactive Oxidized\n                    <i>Polygonati Rhizoma<\/i>\n                    Polysaccharide Crosslinked Chitosan Hydrogel as Therapeutic Carrier for Parkinson's Disease Treatment"],"prefix":"10.1002","author":[{"given":"Peng","family":"Dai","sequence":"first","affiliation":[{"name":"Central Laboratory of the Medical Research Center The First Affiliated Hospital of Ningbo University  Ningbo 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