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The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH\u2010induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally\u2010injected multifunctional hydrogel that can efficiently co\u2010load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti\u2010inflammation, reactive oxygen species (ROS)\u2010removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS\u2010responsive crosslinker to form amphiphilic polymer that self\u2010assemble into particles with ropivacaine loaded into the core. Solution of drug\u2010loaded particles and thermo\u2010sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro\u2010inflammatory cytokines and pain\u2010related molecules including cyclooxygenase\u20102 (COX\u20102) and prostaglandin E2 (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ). Therapeutic hydrogel suppresses the LDH\u2010induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine\u2010related diseases.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202401227","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T07:41:58Z","timestamp":1720510918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Paravertebrally\u2010Injected Multifunctional Hydrogel for Sustained Anti\u2010Inflammation and Pain Relief in Lumbar Disc Herniation"],"prefix":"10.1002","volume":"13","author":[{"given":"Wenhao","family":"Deng","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow University  199 Ren Ai Road, Suzhou Industrial Park Suzhou 215123 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianpeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Soochow University  1055 San\u2010Xiang Road Suzhou 215004 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinli","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow University  199 Ren Ai Road, Suzhou Industrial Park Suzhou 215123 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Soochow University  1055 San\u2010Xiang Road Suzhou 215004 P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6545-7867","authenticated-orcid":false,"given":"Yiran","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow University  199 Ren Ai Road, Suzhou Industrial Park Suzhou 215123 P. R. 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