Intervertebral disc degeneration (IVDD) is a prevalent chronic spinal condition characterized by the deterioration of the intervertebral discs (IVD), leading to structural damage and associated pain. This degenerative process is closely linked to oxidative stress injury, which plays a pivotal role in its onset and progression. Oxidative stress in IVDD results from the excessive production of reactive oxygen species (ROS) and impaired ROS clearance mechanisms, disrupting the redox balance within the intervertebral disc. Consequently, oxidative stress contributes to the degradation of the extracellular matrix (ECM), promotes cell apoptosis, and exacerbates disc tissue damage. Current treatment options for IVDD face significant challenges in effectively alleviating the oxidative stress-induced damage and facilitating disc tissue repair. However, recent advancements in biomaterials have opened new avenues of hope for IVDD treatment by addressing oxidative stress. In this review, we first provide an overview of the pathophysiological process of IVDD and explore the mechanisms and pathways associated with oxidative stress injury. Then, we delve into the current research on antioxidant biomaterials employed in the treatment of IVDD, and outline the advantages and limitations of hydrogel, nanomaterials, polyphenol and inorganic materials. Finally, we propose the future research direction of antioxidant biomaterials in IVDD treatment. The main idea of this review is shown in Scheme 1.

Spinal cord injury (SCI) causes neuroinflammation, neuronal death, and severe axonal connections. Alleviating neuroinflammation, protecting residual cells and promoting neuronal regeneration via endogenous neural stem cells (eNSCs) represent potential strategies for SCI treatment. Extracellular vesicles (EVs) released by mesenchymal stem cells have emerged as pathological mediators and alternatives to cell-based therapies following SCI. In the present study, EVs isolated from untreated (control, C-EVs) and TGF-β1-treated (T-EVs) mesenchymal stem cells were injected into SCI mice to compare the therapeutic effects and explore the underlying mechanisms. Our study demonstrated for the first time that the application of T-EVs markedly enhanced the proliferation and antiapoptotic ability of NSCs in vitro. The infusion of T-EVs into SCI mice increased the shift from the M1 to M2 polarization of reactive microglia, alleviated neuroinflammation, and enhanced the neuroprotection of residual cells during the acute phase. Moreover, T-EVs increased the number of eNSCs around the epicenter. Consequently, T-EVs further promoted neurite outgrowth, increased axonal regrowth and remyelination, and facilitated locomotor recovery in the chronic stage. Furthermore, the use of T-EVs in Rictor^−/− SCI mice (conditional knockout of Rictor in NSCs) showed that T-EVs failed to increase the activation of eNSCs and improve neurogenesis sufficiently, which suggested that T-EVs might induce the activation of eNSCs by targeting the mTORC2/Rictor pathway. Taken together, our findings indicate the prominent role of T-EVs in the treatment of SCI, and the therapeutic efficacy of T-EVs for SCI treatment might be optimized by enhancing the activation of eNSCs via the mTORC2/Rictor signaling pathway.

The poor survival and low efficiency of neuronal differentiation limits the therapeutic effects of transplanted neural stem cells in the treatment of spinal cord injury. Neurofibromatosis-1 (NF-1) is a tumor suppressor gene that restricts the rapid and abnormal growth and differentiation of neural cells. In the present study, lentiviral vectors were used to knock out NF-1, Ricotr (the core member of mTORC2) or NF-1+Ricotr in neural stem cells in vitro, and the NF-1, Ricotr or NF-1+Ricotr knockout neural stem cells were transplanted at the lesion site in a rat model of spinal cord injury (SCI). We first demonstrated that targeted knockout of NF-1 had an antiapoptotic effect and improved neuronal differentiation by enhancing the mTORC2/Rictor pathway of neural stem cells in vitro. Subsequently, transplanting NF-1 knockout neural stem cells into the injured site sufficiently promoted the tissue repair and functional recovery of rats with spinal cord injury by enhancing the survival and neuronal differentiation of grafted neural stem cells. Collectively, these findings reveal a prominent role of NF-1 in neural stem cell biology, which is an invaluable step forward in enhancing the benefit of neural stem cell-mediated regenerative cell therapy for spinal cord injury and identifies the transplantation of NF-1 knockout neural stem cells as a promising strategy for spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202511000-00030/figure1/v/2026-04-24T022020Z/r/image-tiff We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury. While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function, their precise function in spinal cord injury remains unclear. To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury, we conducted single-cell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury. Subsequently, we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16–17 days and extracted exosomes. The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes. Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs, 104 long non-coding RNAs, 720 circular RNAs, and 14 microRNAs compared with the control group. Construction of a competing endogenous RNA network identified the following hub genes: tuberous sclerosis 2 ( Tsc2 ), solute carrier family 16 member 3 ( Slc16a3 ), and forkhead box protein P1 ( Foxp1 ). Notably, a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury. TSC2-positive cells were localized around SRY-box transcription factor 2–positive cells within the injury zone. Furthermore, in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells. Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways. In addition, Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways. Collectively, these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.