Biomimetic Microstructural Materials for Intervertebral Disk Degeneration Repair DOI Creative Commons
Ang Li, Hui Yuan, Feng Cai

et al.

Small Structures, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

The intervertebral disks (IVD) serve as shock absorbers in the spine. As largest avascular tissue human body, it has a limited capacity for regeneration. To address this issue, various innovative biomimetic materials have been explored to facilitate IVD regeneration at both microscopic and macroscopic levels. Techniques such electrostatic spinning fiber‐winding machines employed prepare materials. In review, physiological structure of is described, advanced studies on its microstructure are summarized. techniques used biomaterial development further investigated, that systematically explored. Specifically, article provides detailed description summary key features materials, including types loads they can withstand their regenerative effects. Finally, prospective outlook application presented.

Language: Английский

The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications DOI Creative Commons
Xiang‐Long Chen, Anran Zhang, Kangcheng Zhao

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 98, P. 102323 - 102323

Published: May 9, 2024

Oxidative stress is one of the main driving mechanisms intervertebral disc degeneration(IDD). has been associated with inflammation in disc, cellular senescence, autophagy, and epigenetics cells. It above pathological are closely linked through common hub reactive oxygen species(ROS), promote each other process degeneration development disease. This reveals important role oxidative IDD, importance great potential IDD therapy targeting stress. The efficacy traditional unstable or cannot be maintained. In recent years, due to rise materials science, many bioactive functional have applied treatment combination drugs, satisfactory achieved. At present, research review antioxidant not complete. Based on existing studies, mechanism were summarized this paper, strategies based emerging reviewed.

Language: Английский

Citations

24
A Redox Homeostasis Modulatory Hydrogel with GLRX3+ Extracellular Vesicles Attenuates Disc Degeneration by Suppressing Nucleus Pulposus Cell Senescence DOI
Can Liu,

Lei Fan,

Ming Guan

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(14), P. 13441 - 13460

Published: July 11, 2023

Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments are absent. Here, we found that Glutaredoxin3 (GLRX3) an important redox-regulating molecule associated with NP degeneration. Using hypoxic preconditioning method, developed GLRX3+ mesenchymal stem cell-derived vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing reactive oxygen species (ROS) accumulation cascade expansion in vitro. Further, tissue-like biopolymer-based supramolecular hydrogel, was injectable, degradable, ROS-responsive, proposed to deliver EVs-GLRX3 treating rat model of degeneration, demonstrated EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated state, restored ECM deposition modulating redox homeostasis. Our findings suggested modulation homeostasis can rejuvenate attenuate

Language: Английский

Citations

39
Exosome-laden injectable self-healing hydrogel based on quaternized chitosan and oxidized starch attenuates disc degeneration by suppressing nucleus pulposus senescence DOI Creative Commons
Ming Guan, Can Liu, Qiangqiang Zheng

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 232, P. 123479 - 123479

Published: Jan. 30, 2023

Disc degeneration is the common pathology underlying various degenerative spinal disorders and currently there no effective cure. Here, we found nucleus pulposus (NP) cell senescence was closely associated with severity of disc degeneration, exosomes (Exos) derived from mesenchymal stem cells (MSCs) ameliorated NP promoted extracellular matrix (ECM) deposition. As chitosan-based hydrogels have been widely used as vehicles to deliver Exos due their prominent antibacterial capacity, biocompatibility, biodegradability, developed an Exos-laden hydrogel based on quaternized chitosan (QCS) oxidized starch (OST) treat degeneration. The synthesized QCS-OST injectable, self-healing, biocompatible, demonstrated desirable pore size, injectable properties, sustainable release Exos. In a rat model QCS-OST/Exos able rejuvenate senescence, promote ECM remodeling, partially restore structures annulus fibrosis. Our findings suggested that novel therapeutic strategy for treating via alleviating senescence.

Language: Английский

Citations

32
Rapidly in situ forming an injectable Chitosan/PEG hydrogel for intervertebral disc repair DOI Creative Commons
Lin Huang,

Wantao Wang,

Yiwen Xian

et al.

Materials Today Bio, Journal Year: 2023, Volume and Issue: 22, P. 100752 - 100752

Published: July 28, 2023

Intervertebral disc (IVD) degeneration occurred with the increasing age or accidents has puzzled peoples in daily life. To seal IVD defect by injectable hydrogels is a promising method for slowing down degeneration. Herein, we reported rapidly situ forming chitosan/PEG hydrogel (CSMA-PEGDA-L) through integrating photo-crosslink of methacrylate chitosan (CSMA) Schiff base reaction between CSMA and aldehyde polyethylene glycol (PEGDA). The CSMA-PEGDA-L possessed stronger compressive strength than photo-crosslinked CSMA-L Schiff-base-crosslinked CSMA-PEGDA hydrogel. This showed low cytotoxicity from incubation experiments nucleus pulpous cells. When implanted on punctured rat's tail, could well retard progression physical plugging, powerfully proven radiological histological evaluations. work demonstrated strategy glue may be potential solution prevention

Language: Английский

Citations

27
Core–Shell Structured Nanozyme with PDA-Mediated Enhanced Antioxidant Efficiency to Treat Early Intervertebral Disc Degeneration DOI
Jing Wang, Ruibang Wu, Zheng Liu

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(4), P. 5103 - 5119

Published: Jan. 17, 2024

Early intervention during intervertebral disc degeneration (IDD) plays a vital role in inhibiting its deterioration and activating the regenerative process. Aiming at high oxidative stress (OS) IDD microenvironment, core–shell structured nanozyme composed of Co-doped NiO nanoparticle (CNO) as core encapsulated with polydopamine (PDA) shell, named PDA@CNO, was constructed, hoping to regulate pathological environment. The results indicated that coexistence abundant Ni3+/Ni2+and Co3+/Co2+redox couples CNO provided rich catalytic sites; meanwhile, quinone catechol groups PDA shell could enable proton-coupled electron transfer, thus endowing PDA@CNO multiple antioxidative enzyme-like activities scavenge •O2–, H2O2, •OH efficiently. Under OS conditions vitro, effectively reduce intracellular ROS nucleus pulposus (NP) into friendly H2O O2, protect NP cells from stagnant proliferation, abnormal metabolism (senescence, mitochondria dysfunction, impaired redox homeostasis), inflammation, thereby reconstructing extracellular matrix (ECM) homeostasis. vivo local injection experiments further proved desirable therapeutic effects rat model, suggesting great potential prohibiting deterioration.

Language: Английский

Citations

9
Injectable Hydrogel Based on Enzymatic Initiation of Keratin Methacrylate for Controlled Exosome Release in Intervertebral Disc Degeneration Therapy DOI
Linjie Chen, Ke Peng,

He Huang

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(32)

Published: April 5, 2024

Abstract The treatment of intervertebral disc degeneration (IVDD) using bone marrow mesenchymal stem cell‐derived exosomes has shown success in alleviating inflammation and restoring the extracellular matrix (ECM), however, challenges persist due to deficiency mechanical support controlled release. Herein, a carbon‐carbon double bond modified keratin (KeMA) is synthesized by 2‐isocyanatoethyl modification for wrapping. This injectable KeMA hydrogel, initiated biocompatible glucose/ glucose oxidase/ horse radish peroxidase enzymatic cascade reaction with acetylacetone N‐vinylpyrrolidone, displayed rapid gelation, resembling nucleus pulposus (NP) elasticity, excellent cytocompatibility. In vitro studies showcased that exosomes‐loaded hydrogel (Exo@KeMA) enhanced exosome release kinetics, suppressed inflammation, fostered (ECM) regeneration, reinstated NP biomechanics. RNA‐seq analysis indicated Exo@KeMA's effects involved PI3K‐Akt signaling regeneration NF‐κB inhibition anti‐inflammation. vivo IVDD rat models demonstrated Exo@KeMA attenuated maintained water content, preserved height, promoted structural regeneration. research introduces an as promising therapy IVDD, facilitating biomechanics restoration, anti‐inflammatory response, ECM

Language: Английский

Citations

8
Single-Cell Microgel Encapsulation Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in Treating Intervertebral Disc Degeneration via Inhibiting Pyroptosis DOI Creative Commons
Guanrui Huang, Haotian Shen,

Kaiwang Xu

et al.

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

While mesenchymal stem cell (MSC) shows great potentials in treating intervertebral disc degeneration, most MSC die soon after intradiscal transplantation, resulting inferior therapeutic efficacy. Currently, bulk hydrogels are the common solution to improve survival tissues, although hydrogel encapsulation impairs migration and disrupts extracellular microenvironment. Cell has been proposed overcome limitation of traditional hydrogels, yet this technique not used degeneration. Using a layer-by-layer self-assembly technique, we fabricated alginate gelatin microgel encapsulate individual for The small size allowed injection coated MSC. We demonstrated that pyroptosis was involved death under oxidative stress stimulation, coating suppressed activation by maintaining mitochondria homeostasis. Microgel protected harsh microenvironment, while retaining vital cellular functions such as migration, proliferation, differentiation. In rat model exhibits prolonged retention better efficacy attenuating compared with bare treatment alone. Further, microgel-coated exhibited improved effects degeneration via suppressing disc. For first time, microgel-encapsulated treat obtain encouraging outcomes. developed biocompatible single-cell is an effective strategy protect maintain may be efficacious approach improving therapy objective study using further understand related cytoprotective mechanisms.

Language: Английский

Citations

6
Viscoelastic hydrogels regulate adipose-derived mesenchymal stem cells for nucleus pulposus regeneration DOI Creative Commons
Yin Liu, Li Li, Xuan Li

et al.

Acta Biomaterialia, Journal Year: 2024, Volume and Issue: 180, P. 244 - 261

Published: April 12, 2024

Low back pain is a leading cause of disability worldwide, often attributed to intervertebral disc (IVD) degeneration with loss the functional nucleus pulposus (NP). Regenerative strategies utilizing biomaterials and stem cells are promising for NP repair. Human tissue highly viscoelastic, relaxing stress rapidly under deformation. However, impact tissue-specific viscoelasticity on activities adipose-derived (ASC) remains largely unexplored. Here, we investigated role matrix in regulating ASC differentiation IVD regeneration. Viscoelastic alginate hydrogels relaxation time scales ranging from 100s 1000s were developed used culture human ASCs 21 days. Our results demonstrated that fast-relaxing hydrogel significantly enhanced long-term cell survival NP-like extracellular secretion aggrecan type-II collagen. Moreover, gene expression analysis revealed substantial upregulation mechanosensitive ion channel marker TRPV4 NP-specific markers such as SOX9, HIF-1α, KRT18, CDH2 CD24 cultured within hydrogel, compared slower-relaxing hydrogels. These findings highlight critical behavior suggest key parameter novel design improve efficacy therapy •Systematically characterized influence tissue-mimetic ASC. •NP-mimetic tunable tissue-matched stiffness. •Long-term metabolic activity substantially improved hydrogel. •The allows higher rate protrusions formation remodeling. •ASC towards an phenotype promoted more positive indicating committed fate. TRPV4, molecular sensor viscoelasticity, sensing during development. ECM considerably influenced by where deposition collagen

Language: Английский

Citations

6
Dynamic Dual-Network Hydrogel Microspheres for Enhanced Nucleus Pulposus Regeneration Via Extracellular Matrix Mimicry DOI
Xin Tian, Hao Liu, Chenyang Jin

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Single-cell RNA sequencing-guided engineering of mitochondrial therapies for intervertebral disc degeneration by regulating mtDNA/SPARC-STING signaling DOI
Guoyu Yang,

Chenpeng Dong,

Zhaoxi Wu

et al.

Bioactive Materials, Journal Year: 2025, Volume and Issue: 48, P. 564 - 582

Published: March 1, 2025

Language: Английский

Citations

0