Exercise Mimetic Exosomes Re‐establish the Extracellular Matrix Metabolic Balance and Alleviate the Inflammatory Macrophage Infiltration in Intervertebral Disc Degeneration DOI
Ke Zhao, Yongzhi Cui, Yuxuan Du

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Abstract Extracellular matrix (ECM) metabolic imbalance and macrophage infiltration, induced by degenerated nucleus pulposus cells (NPCs), represent key pathological alterations in intervertebral disc degeneration (IVDD). Physical exercise is shown to effectively delay the progression of IVDD enhancing ECM synthesis reducing inflammation. However, many individuals are unable maintain regular habits due physical limitations insufficient self‐discipline. In response this challenge, concept mimetic exosomes (EMEs) proposed as a therapeutic strategy for IVDD. approach, human pluripotent stem cell‐derived myotubes subjected mechanical strain simulate conditions. The generated under these conditions, termed EMEs, enriched with exercise‐inducible components, notably irisin. These EMEs capable being internalized both NPCs macrophages. NPCs, restored balance inhibited NFκB activation. macrophages, modulated M1 polarization NPCs. Collectively, equilibrium extracellular mitigated inflammatory infiltration within microenvironment, thereby demonstrating significant effects on More importantly, may serve model treatment other musculoskeletal disorders development therapies.

Language: Английский

Preserving the Immune‐Privileged Niche of the Nucleus Pulposus: Safeguarding Intervertebral Discs from Degeneration after Discectomy with Synthetic Mucin Hydrogel Injection DOI Creative Commons
Huan Wang, Song Chen, Zhao Liu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(43)

Published: Aug. 29, 2024

Abstract Intervertebral disc (IVD) herniation is a prevalent spinal disorder, often necessitating surgical intervention such as microdiscectomy for symptomatic relief and nerve decompression. IVDs comprise gel‐like nucleus pulposus (NP) encased by an annulus fibrosus (AF), their avascular nature renders them immune‐privileged. Microdiscectomy exposes the residual NP to immune system, precipitating cell infiltration attack that exacerbates IVD degeneration. While many efforts in tissue engineering field are directed toward regeneration, inherently limited regenerative capacity due low‐cellularity of challenging mechanical environment spine impedes success. This study, aiming prevent degeneration post‐microdiscectomy, utilizes mucin‐derived gels (Muc‐gels) form gel at site, inspired natural mucin coating on living organisms evade reorganization. It shown type I macrophages present severely degenerated human discs. Encapsulating within Muc‐gels prevents fibrous encapsulation macrophage mouse subcutaneous model. The injection rat tail model up 24 weeks post‐operation. Mechanistic investigations indicate attenuate into NPs, offering durable protection against post‐microdiscectomy.

Language: Английский

Citations

6
Multidimensional exploration of hydrogels as biological scaffolds for spinal cord regeneration: mechanisms and future perspectives DOI Creative Commons
Cheng Han, Jiao Jiao, Chan Gong

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: April 23, 2025

Spinal cord injury (SCI) is a severe condition that frequently leads to permanent disabilities and neurological dysfunction. Its progression driven by multifaceted pathophysiology, encompassing direct trauma, secondary cascades, intricate cellular molecular responses. While current therapies focus on alleviating symptoms restoring functionality, achieving effective neural regeneration in the spinal continues be significant challenge. Hydrogels, recognized for their exceptional biocompatibility, conductivity, injectability, have shown great potential as advanced scaffolds support neuronal axonal regeneration. Recently, these materials attracted interest field of SCI rehabilitation research. This review concludes recent progress hydrogel-based strategies rehabilitation, emphasizing distinct properties, underlying mechanisms, integration with bioactive molecules, stem cells, complementary biomaterials. Hydrogels foster providing tailored microenvironment, while features such self-repair, electrical controlled drug release significantly enhance therapeutic experimental models. explores hydrogel technologies applications, underscoring address challenges treatment paving way future clinical implementation.

Language: Английский

Citations

0
Exploring the molecular mechanisms underlying intervertebral disc degeneration by analysing multiple datasets DOI Creative Commons

Longquan Lin,

Da Li,

Gangfeng Cai

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 28, 2025

The purpose of this study was to explore the genetic characteristics and immune cell infiltration related intervertebral disc degeneration through multidataset analysis, predict potential therapeutic drugs, provide a theoretical basis for clinical treatment. gene expression profile data GSE70362, GSE186542, GSE245147 datasets were downloaded from Gene Expression Omnibus (GEO) database, hub genes identified differentially expressed Ontology (GO) Kyoto Encyclopaedia Genes Genomes (KEGG) functional annotation Mendelian randomization analysis performed. Hub cells identified. Infiltration status determined GSEA GSVA clarify specific signalling pathways associated with key molecular mechanisms by which affect disease progression. reversely predicted using miRNA grid construction transcription factor regulation, regulation obtained GeneCards database. Finally, used drug prediction Connectivity Map database identify drugs treatment degeneration. feasibility tested docking technology. Real-time quantitative PCR confirm in tissue samples.A total 126 GEO 4 (COL6A2, DCXR, GLRX, PDGFRB) bioinformatics methods. Immune revealed that NK cells, macrophages, eosinophils activated during IVDD, whereas mast T suppressed. GO KEGG analyses are involved development such as glycolysis pathway, oxidative phosphorylation cholesterol regulatory haem metabolism pathway. Analysis constructed jointly regulated multiple factors, among most important motif is cisbp_M5578. Disease regulation-related correlation performed, levels two mRNA significantly correlated. performed Abt-751, LY-2183240, podophyllotoxin, vindesine can alleviate or even reverse state. we collected 10 IVDD healthy samples, RT‒qPCR results consistent results. We COL6A2, PDGFRB IVDD. In addition, Abt-751 expected control progression disease. future, these may new directions further mechanistic studies well therapies patients.

Language: Английский

Citations

0
Engineering extracellular matrix-based hydrogels for intervertebral disc regeneration DOI Creative Commons

Mwafaq Kmail,

Rusydi Razak,

Isma Liza Mohd Isa

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: May 1, 2025

Lower back pain (LBP) is a major health concern, especially in older adults. A key aetiological factor intervertebral disc (IVD) degeneration. It mediated by dysregulation of extracellular matrix (ECM) and inflammation. In recent years, regenerative therapies have garnered attention for their potential to restore function addressing the underlying biological alterations within IVD. This review focuses on comprehensive understanding anatomy physiology IVD, highlighting its life cycle from embryonic development, maturation degenerative phenotype. We describe current treatments managing LBP caused IVD emphasizes advancements hydrogel engineering, natural, synthetic, composite hydrogels application ECM-targeted therapy By exploring innovations technology, including improvements crosslinking techniques controlled degradation rates-we discuss how these materials could enhance regeneration potentially be used management LBP. With enhanced biomimicry, hydrogel-based ECM mimics offer promising pathway developing effective, durable that address root causes degeneration, providing new hope individuals living with chronic

Language: Английский

Citations

0
NanoCRISPR-Assisted Biomimetic Tissue-Equivalent Patch Regenerates the Intervertebral Disc by Inhibiting Endothelial-to-Mesenchymal Transition DOI
Yong Huang, Hao Li, Lin Qi

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 322, P. 123404 - 123404

Published: May 14, 2025

Language: Английский

Citations

0
Exercise Mimetic Exosomes Re‐establish the Extracellular Matrix Metabolic Balance and Alleviate the Inflammatory Macrophage Infiltration in Intervertebral Disc Degeneration DOI
Ke Zhao, Yongzhi Cui, Yuxuan Du

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Abstract Extracellular matrix (ECM) metabolic imbalance and macrophage infiltration, induced by degenerated nucleus pulposus cells (NPCs), represent key pathological alterations in intervertebral disc degeneration (IVDD). Physical exercise is shown to effectively delay the progression of IVDD enhancing ECM synthesis reducing inflammation. However, many individuals are unable maintain regular habits due physical limitations insufficient self‐discipline. In response this challenge, concept mimetic exosomes (EMEs) proposed as a therapeutic strategy for IVDD. approach, human pluripotent stem cell‐derived myotubes subjected mechanical strain simulate conditions. The generated under these conditions, termed EMEs, enriched with exercise‐inducible components, notably irisin. These EMEs capable being internalized both NPCs macrophages. NPCs, restored balance inhibited NFκB activation. macrophages, modulated M1 polarization NPCs. Collectively, equilibrium extracellular mitigated inflammatory infiltration within microenvironment, thereby demonstrating significant effects on More importantly, may serve model treatment other musculoskeletal disorders development therapies.

Language: Английский

Citations

0