PurposeTo construct an injectable, sustained-release fibrin gel containing rhein to solve the problem of low bioavailability of rhein, and observe its efficacy in the treatment of intervertebral disc degeneration.MethodsThe fibrin gel containing rhein was first synthesized in advance. Subsequently, the materials were characterized by various experimental methods. Secondly, the degenerative cell model was constructed by stimulating nucleus pulposus cells with lipopolysaccharide (LPS), and the corresponding intervention treatment was carried out to observe the effect in vitro. Finally, the rat tail intervertebral disc was acupunctured by needles to establish the intervertebral disc degeneration model, and the effect of the material was observed through intradiscal injection.ResultsThe fibrin glue containing rhein (rhein@FG) showed good injectability, sustained release and biocompatibility. Rhein@FG can improve the LPS-induced inflammatory microenvironment, regulate ECM metabolic disorders of nucleus pulposus cells and aggregation of the NLRP3 inflammasome in vitro, and inhibit cell pyroptosis. Furthermore, in vivo experiments, rhein@FG effectively prevented needle puncture-induced intervertebral disc degeneration in rats.ConclusionsRhein@FG has better efficacy than rhein or FG alone due to its slow release and mechanical properties, which can be used as a potential replacement therapy for intervertebral disc degeneration.Graphical Abstract