Extracellular vesicles deliver thioredoxin to rescue stem cells from senescence and intervertebral disc degeneration a feed-forward circuit of the NRF2/AP-1 composite pathway.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown.

Alleviation of inflammation in paraventricular nucleus and sympathetic outflow by melatonin efficiently repairs endplate porosities and attenuates spinal hyperalgesia.

Low back pain, largely attributed to intervertebral disc (IVD) degeneration, is correlated with increased sympathetic nerve activity. Toll-like receptor 4 (TLR4)-mediated inflammation in the paraventricular nucleus (PVN) triggers sympathetic nerve activation, which remains uncharted in IVD degeneration. We hypothesized that lumbar spine instability (LSI) surgery in mice elevated sympathetic outflow by activating TLR4/NF-κB axis in PVN, and exacerbated endplate porosities and spinal hyperalgesia following 4 or 8 weeks LSI surgery.

SP1/CTR1-mediated oxidative stress-induced cuproptosis in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is an age-related disease and is responsible for low back pain. Oxidative stress-induced cell death plays a fundamental role in IDD pathogenesis. Cuproptosis is a recently discovered form of programmed cell death dependent on copper availability.

Nucleus pulposus cells regulate macrophages in degenerated intervertebral discs via the integrated stress response-mediated CCL2/7-CCR2 signaling pathway.

Lower back pain (LBP), which is a primary cause of disability, is largely attributed to intervertebral disc degeneration (IDD). Macrophages (MΦs) in degenerated intervertebral discs (IVDs) form a chronic inflammatory microenvironment, but how MΦs are recruited to degenerative segments and transform into a proinflammatory phenotype remains unclear. We evaluated chemokine expression in degenerated nucleus pulposus cells (NPCs) to clarify the role of NPCs in the establishment of an inflammatory microenvironment in IDD and explored the mechanisms.

An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain.

The progressive worsening of disc degeneration and related nonspecific back pain are prominent clinical issues that cause a tremendous economic burden. Activation of reactive oxygen species (ROS) related inflammation is a primary pathophysiologic change in degenerative disc lesions. This pathological state is associated with M1 macrophages, apoptosis of nucleus pulposus cells (NPC), and the ingrowth of pain-related sensory nerves.

Enzymatically Bioactive Nucleus Pulposus Matrix Hydrogel Microspheres for Exogenous Stem Cells Therapy and Endogenous Repair Strategy to Achieve Disc Regeneration.

Exogenous stem cell therapy and endogenous repair has shown great potential in intervertebral disc regeneration. However, limited nutrients and accumulation of lactate largely impair the survival and regenerative capacity of implanted stem cells and endogenous nucleus pulposus cells (NPCs). Herein, an injectable hydrogel microsphere (LMGDNPs) have been developed by immersing lactate oxidase (LOX)-manganese dioxide (MnO ) nanozyme (LM) into glucose-enriched decellularized nucleus pulposus hydrogel microspheres (GDNPs) through a microfluidic system.

Multifunctional annulus fibrosus matrix prevents disc-related pain via inhibiting neuroinflammation and sensitization.

Chronic low back pain mainly attributed to intervertebral disc (IVD) degeneration. Endogenous damage-associated molecular patterns (DAMPs) in the injured IVD, particularly mitochondria-derived nucleic acid molecules (CpG DNA), play a primary role in the inflammatory responses in macrophages. M1-type macrophages form a chronic inflammatory microenvironment by releasing pro-inflammatory factors and nerve growth factor (NGF) that induce nerve growth into the inner annulus fibrosus, resulting in persistent hyperalgesia.

Extracellular Vesicle-Conjugated Functional Matrix Hydrogels Prevent Senescence by Exosomal miR-3594-5p-Targeted HIPK2/p53 Pathway for Disc Regeneration.

Nucleus pulposus stem cells (NPSCs) senescence plays a critical role in the progression of intervertebral disc degeneration (IDD). Stem cell-derived extracellular vesicles (EV) alleviate cellular senescence. Whereas, the underlying mechanism remains unclear.

Endogenous repair theory enriches construction strategies for orthopaedic biomaterials: a narrative review.

The development of tissue engineering has led to new strategies for mitigating clinical problems; however, the design of the tissue engineering materials remains a challenge. The limited sources and inadequate function, potential risk of microbial or pathogen contamination, and high cost of cell expansion impair the efficacy and limit the application of exogenous cells in tissue engineering. However, endogenous cells in native tissues have been reported to be capable of spontaneous repair of the damaged tissue.

Proper animal experimental designs for preclinical research of biomaterials for intervertebral disc regeneration.

Low back pain is a vital musculoskeletal disease that impairs life quality, leads to disability and imposes heavy economic burden on the society, while it is greatly attributed to intervertebral disc degeneration (IDD). However, the existing treatments, such as medicines, chiropractic adjustments and surgery, cannot achieve ideal disc regeneration. Therefore, advanced bioactive therapies are implemented, including stem cells delivery, bioreagents administration, and implantation of biomaterials etc.

IGF Signaling in Intervertebral Disc Health and Disease.

Low back pain (LBP) is a common musculoskeletal symptom, which brings a lot of pain and economic loss to patients. One of the most common causes of LBP is intervertebral disc degeneration (IVDD). However, pathogenesis is still debated, and therapeutic options are limited.

A predictive model with a risk-classification system for cancer-specific survival in patients with primary osteosarcoma of long bone.

Background: Osteosarcoma (OS), most commonly occurring in long bone, is a group of malignant tumors with high incidence in adolescents. No individualized model has been developed to predict the prognosis of primary long bone osteosarcoma (PLBOS) and the current AJCC TNM staging system lacks accuracy in prognosis prediction. We aimed to develop a nomogram based on the clinicopathological factors affecting the prognosis of PLBOS patients to help clinicians predict the cancer-specific survival (CSS) of PLBOS patients.

Corrigendum to 'Decellularized disc hydrogels for hBMSC tissue-specific differentiation and tissue regeneration' [Bioactive Materials 6 (2021) 3541-3556].

[This corrects the article DOI: 10.1016/j.bioactmat.

Glucagon-like peptide-1 receptor activation maintains extracellular matrix integrity by inhibiting the activity of mitogen-activated protein kinases and activator protein-1.

Disruption of the intervertebral disc extracellular matrix (ECM) is a hallmark of intervertebral disc degeneration (IDD), which is largely attributed to excessive oxidative stress. However, there is a lack of clinically feasible approaches to promote the reconstruction of the disc ECM. Glucagon-like peptide-1 (GLP-1), a safe polypeptide hormone adopted to treat type 2 diabetes mellitus, has shown great potential for relieving oxidative stress-related damage.

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration.

Tissue specificity, a key factor in the decellularized tissue matrix (DTM), has shown bioactive functionalities in tuning cell fate-e.g., the differentiation of mesenchymal stem cells.

Reactive Oxygen Species Regulate Endoplasmic Reticulum Stress and ER-Mitochondrial Ca Crosstalk to Promote Programmed Necrosis of Rat Nucleus Pulposus Cells under Compression.

Programmed necrosis of nucleus pulposus (NP) cells caused by excessive compression is a crucial factor in the etiopathogenesis of intervertebral disc degeneration (IVDD). The endoplasmic reticulum (ER) and mitochondria are crucial regulators of the cell death signaling pathway, and their involvement in IVDD has been reported. However, the specific role of ER stress (ERS) and ER-mitochondria interaction in compression-induced programmed necrosis of NP cells remains unknown.

Resveratrol-enhanced SIRT1-mediated osteogenesis in porous endplates attenuates low back pain and anxiety behaviors.

Low back pain (LBP) is a major clinical problem that lacks effective treatments. The sensory innervation in porous vertebral endplates and anxiety contributes to spinal hyperalgesia. We hypothesized that SIRT1 activator resveratrol alleviates LBP and anxiety via promotion of osteogenesis in the porous endplates.

Enhancement of mechanical and biological performance on hydroxyapatite/silk fibroin scaffolds facilitated by microwave-assisted mineralization strategy.

Three-dimensional (3D) porous hydroxyapatite/silk fibroin (HA/SF) composite scaffolds with good mechanical and biological performance, could provide a good cellular survival microenvironment for bone repair. However, coating HA efficiently and uniformly on SF scaffolds remains a challenge. In this study, the effects of microwave-assisted technology and biomineralization methods on the nanostructure, chemical composition and deposition efficiency of HA coating have been comparatively analyzed.

Puerarin Relieved Compression-Induced Apoptosis and Mitochondrial Dysfunction in Human Nucleus Pulposus Mesenchymal Stem Cells via the PI3K/Akt Pathway.

Puerarin (PUR), an 8-C-glucoside of daidzein extracted from Pueraria plants, is closely related to autophagy, reduced reactive oxygen species (ROS) production, and anti-inflammatory effects, but its effects on human nucleus pulposus mesenchymal stem cells (NPMSCs) have not yet been identified. In this study, NPMSCs were cultured in a compression apparatus to simulate the microenvironment of the intervertebral disc under controlled pressure (1.0 MPa), and we found that cell viability was decreased and apoptosis level was gradually increased as compression duration was prolonged.

Correction to: LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway.

In the original publication of this manuscript [1], Fig. 5a needs to be revised, and adjustments have also been made to the captions for Figs. 2, 4, 5 and S1 to improve clarity for the reader.

Delivery of MutT homolog 1 inhibitor by functionalized graphene oxide nanoparticles for enhanced chemo-photodynamic therapy triggers cell death in osteosarcoma.

Photodynamic therapy (PDT) generates highly toxic reactive oxygen species (ROS) during noninvasive cancer treatment. MutT homolog 1 (MTH1) protein is a DNA oxidative damage repair protease and suppressing its function may provide a strategy to enhance PDT efficacy by improving cellular sensitivity to ROS. A nanoparticle, composed of functional graphene oxide (GO) conjugated with polyethylene glycol (PEG), folic acid (FA) and photosensitizer indocyanine green (ICG), was constructed to deliver MTH1 inhibitor (TH287) and doxorubicin.

Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells.

Stem cell therapy, which promotes stem cells differentiation toward specialized cell types, increases the resident population and production of extracellular matrix, and can be used to achieve intervertebral disc (IVD) repair, has drawn great attention for the development of IVD-regenerating materials. Many materials that have been reported in IVD repair have the ability to promote stem cells differentiation. However, due to the limitations of mechanical properties, immunogenicity and uncontrollable deviations in the induction of stem cells differentiation, there are few materials that can currently be translated into clinical applications.

Surface engineering of nanoparticles with ligands for targeted delivery to osteosarcoma.

Osteosarcoma is one of the most common malignant bone tumors which affect adolescents. Neoadjuvant chemotherapy followed by operation has become recommended for osteosarcoma treatment. Whereas, the effects of conventional chemotherapy are unsatisfactory because of multidrug resistance, fast clearance rate, nontargeted delivery, side effects and so on.