Biomaterial-based strategies targeting ferroptosis for alleviating intervertebral disc degeneration: Advances and perspectives

Intervertebral disc degeneration (IVDD), a prevalent degenerative disorder, imposes a substantial and growing health burden in aging populations. Recently, ferroptosis-a regulated cell death driven by lipid peroxidation, iron overload, and glutathione peroxidase 4 (GPX4) dysregulation-has been identified as a key pathogenic mechanism of IVDD. Despite these advances, a comprehensive understanding of its regulatory networks remains limited, hindering the development of targeted therapies and leaving clinical management reliant on invasive surgery. To address these challenges, functional biomaterials have now emerged as a promising strategy with combined anti-ferroptotic effects. In this review, we examine the known ferroptotic mechanisms in IVDD and explore emerging functional biomaterials with combined anti-ferroptotic properties, thereby aiming to advance therapeutic strategies for IVDD. The translational potential of this article: Given the critical role of ferroptosis in IVDD pathogenesis, functional biomaterials represent a promising translational strategy by enabling both targeted delivery of anti-ferroptotic therapeutics and biomaterial-intrinsic protection against ferroptotic damage. By systematically summarizing the ferroptosis-targeting mechanisms, and therapeutic advantages of these biomaterials, this review offers theoretical guidance for the development of future, clinically translatable interventions for IVDD.