Synergistic Modulating of Mitochondrial Transfer and Immune Microenvironment to Attenuate Discogenic Pain

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Discogenic pain, caused by intervertebral disc degeneration (IVDD), is a prevalent and challenging condition to treat effectively. Macrophage infiltration with neural ectopic in‐growth resulting from structural disturbances within the (IVD) major cause of discogenic pain. This work systematically reveals how nanoparticles can synergistically regulate immune microenvironment mitochondrial communication attenuate The antioxidant metal‐polyphenol nanoparticle system sequentially macrophage phenotype delivery efficiency. strategy circumvents necessity for isolation preservation techniques that are typically required in conventional transplantation procedures. Furthermore, it facilitates effective sustained mitochondria damaged cells. In vivo, this formulation effectively preserves IVD height, maintains integrity nucleus pulposus (NP), restores pain thresholds. Thus, nanoplatform offers an approach traditional surgical treatments significant potential clinical application.

Language: Английский

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Injectable ECM-mimetic dynamic hydrogels abolish ferroptosis-induced post-discectomy herniation through delivering nucleus pulposus progenitor cell-derived exosomes

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 1, 2025

Discectomy-induced ferroptosis of nucleus pulposus cells (NPCs) contributes to postoperative lumbar disc herniation (LDH) recurrence and intervertebral degeneration (IDD). We discover that progenitor (NPPCs) could imprint resistance into NPCs through exosome-dependent intercellular transmission miR-221-3p. Based on these findings, we first develop synthetically-tailored NPPC-derived exosomes with enhanced miR-221-3p expression NPC uptake capacity, which are integrated an injectable hydrogel based extracellular matrix (ECM) analogues. The ECM-mimetic (HACS) serves as a biomimetic filler for the post-operative care herniated discs, be facilely injected discectomy-established (NP) cavity localized treatment. HACS-mediated in-situ exosome release in NP enables marked inhibition not only prevents LDH but also reverses IDD symptoms, leading robust restoration structure functions. In summary, this study offers promising approach treating herniation.

Language: Английский

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Impact of asymmetric L4–L5 facet joint degeneration on lumbar spine biomechanics using a finite element approach

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

Published: April 12, 2025

This study investigated the effects of asymmetric facet joint degeneration on spinal behavior and adjacent structures using finite element analysis (FEA). Facet joints play a critical role in providing stability facilitating movement. Degenerative changes these can lead to reduced function pain. Specifically, occurs when one side deteriorates more rapidly due alignment issues, subsequently impacting structures. In this study, grades (G00, G40, G42, G44) were assigned L4-L5 segment simulate during extension, left right lateral bending, axial rotations. As progressed, range motion affected decreased, resulting altered stress distribution across intervertebral discs posterior bone. The showed that bending angle extension decreased with increasing severity. Additionally, corresponding direction while anterior increased. Maximum equivalent disc revealed decreasing trend as worsened, pattern also observed rotation. G40 model, maximum bone L4 L5 exhibited significant disparity between sides. These findings provide quantitative insights into progression degeneration, enhancing our understanding how (FJD) affects

Language: Английский

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Melatonin-loaded self-healing hydrogel targets mitochondrial energy metabolism and promotes annulus fibrosus regeneration

Materials Today Bio, Journal Year: 2023, Volume and Issue: 23, P. 100811 - 100811

Published: Sept. 22, 2023

Intervertebral disc (IVD) herniation is a major cause of chronic low back pain and disability. The current nucleus pulposus (NP) discectomy effectively relieves symptoms, but the annulus fibrosus (AF) defects are left unrepaired. Tissue engineering approaches show promise in treating AF injury IVD degeneration; however, presence an inflammatory milieu at site hinders mitochondrial energy metabolism cells, resulting lack regeneration. In this study, we fabricated dynamic self-healing hydrogel loaded with melatonin (an endocrine hormone well-known for its antioxidant anti-inflammatory properties) investigate whether melatonin-loaded could promote defect repair by rescuing matrix synthesis cells. protective effects on components (e.g. type I II collagen aggrecan) cells were observed interleukin (IL)-1β. Additionally, was found to activate nuclear factor erythroid 2-related signaling pathway, thereby safeguarding function from IL-1β, as evidenced increased level adenosine triphosphate, membrane potential, respiratory chain expression. incorporation into based thiolated gelatin β-cyclodextrin proposed means promoting successful implantation has been shown facilitate situ regeneration tissue, impeding degeneration preserving hydration rat box-cut model. These findings offer compelling evidence that development can functions represents promising strategy

Language: Английский

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Regulating pyroptosis by mesenchymal stem cells and extracellular vesicles: A promising strategy to alleviate intervertebral disc degeneration

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 116001 - 116001

Published: Dec. 20, 2023

Intervertebral disc degeneration (IVDD) is a main cause of low back pain (LBP), which can lead to disability and thus generate heavy burden on society. IVDD characterized by decrease in nucleus pulposus cells (NPCs) endogenous mesenchymal stem (MSCs), degradation the extracellular matrix, macrophage infiltration, blood vessel nerve ingrowth. To date, therapeutic approaches regarding mainly include conservative treatment surgical intervention. However, both only relieve symptoms rather than stop or revert progression IVDD, since pathogenesis not yet clear. Pyroptosis, Caspase family dependence conducted Gasdermin family, newly discovered mode programmed cell death. Pyroptosis has been observed NPCs, annulus fibrosus (AFCs), chondrocytes, MSCs, macrophages, vascular endothelial neurons may contribute IVDD. MSCs are kind pluripotent that be found almost all tissues. have strong ability secrete vesicles (EVs), contain exosomes, microvesicles apoptotic bodies. EVs derived from play an important role pyroptosis regulation could beneficial for alleviating This review focuses clarifying improve MSCs.

Language: Английский

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