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Lactate, a by\u2010product of glycolysis, induces ferroptosis in nucleus pulposus cells (NPCs). Inflammation further enhances glycolysis in NP cells and upregulates lactate dehydrogenase A (LDHA), leading to increased lactate accumulation and the formation of a vicious cycle that accelerates IVDD progression. In this study, an innovative dual\u2010strategy hydrogel system was designed to address these limitations. Phenylboronic acid (PBA) \u2010functionalized G5 PAMAM (G5\u2010PBA) was used to encapsulate LDHA siRNA (siLDHA), forming self\u2010assembled nanoparticles (GPS). Subsequently, GPS was modified with epigallocatechin (EGC) to form stable GPS\u2010EGC nanoparticles through borate ester bonds. The nanoparticles were then incorporated into a reactive oxygen species\u2010 and pH\u2010responsive hydrogel, enabling controlled and sustained drug release. By combining metabolic reprogramming with anti\u2010inflammatory strategies, the designed system not only reduced IL\u20101\u03b2\u2010induced inflammation and lactate production but also alleviated ferroptosis in NPCs and promoted tissue repair in IVDD models. This approach offers a promising therapeutic strategy for IVDD and highlights the potential of material innovation in modulating both metabolic and inflammatory pathways.<\/jats:p>","DOI":"10.1002\/smll.202514952","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:32:36Z","timestamp":1772998356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Dual\u2010Strategy Hydrogel Targeting Glycolytic Reprogramming and Inflammation to Inhibit Ferroptosis and Promote Intervertebral Disc Repair"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7365-3975","authenticated-orcid":false,"given":"Dengbo","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery and Orthopedic Research Institute West China Hospital Sichuan University  Chengdu Sichuan 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