{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T18:11:01Z","timestamp":1787249461118,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The positive feedback circuit between the complement system and inflammatory immune responses maps the malignant progression of chronic joint inflammation. Prolonged dysregulation of the immune microenvironment in rheumatoid arthritis (RA) further exacerbates sustained complement activation, thereby establishing a vicious cycle. In this study, MMP\u20109\u2010responsive, injectable micro\u2010nano geneplexes (C5ASO@HAP\u2010CL\u2010TIMP@HMs) are developed for on\u2010demand regulation of complement component C5, aiming to disrupt this pathological circuit. C5 antisense oligonucleotides (C5ASO) are loaded into cationic liposomes, which are subsequently encapsulated within hyaluronic acid microspheres via click chemistry. In vitro, these geneplexes effectively block abnormal C5 activation in RA synoviocytes, restore macrophage polarization balance, reduce pro\u2010inflammatory cytokine levels and immune complex precursor molecules, and upregulate anti\u2010inflammatory mediators. In an adjuvant\u2010induced arthritis rat model, they significantly alleviate joint swelling and cartilage degradation and suppress inflammatory responses, further highlighting the therapeutic potential of geneplexes in dismantling the complement\u2010inflammation circuit. In summary, the development of micro\u2010nano geneplexes capable of precisely disrupting the complement\u2010inflammatory circuit in RA offers a promising new perspective for the targeted treatment of chronic joint inflammation.<\/jats:p>","DOI":"10.1002\/adma.202518378","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T10:07:09Z","timestamp":1764324429000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Disrupting Complement\u2010Inflammation Positive Feedback Circuit via Oligonucleotide Hydrogel Microspheres for Reversing Joint Inflammation"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4213-8045","authenticated-orcid":false,"given":"Yu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  197 Ruijin 2nd Road Shanghai 200025 P. 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