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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Photothermal Hydrogel with Mn3O4 Nanoparticles Alleviates Intervertebral Disc Degeneration by Scavenging ROS and Regulating Extracellular Matrix Metabolism

Yangyang Chen,Chan Xue,Feifei Ni,Binwu Hu,Miaoheng Yan,He Zhang,Yuxiang Hu,Xiaoyao Peng,Guangfang Li,Yu Han,Hongjian Liu,Zengwu Shao,Qin Wang,Yulong Wei

Annulus fibrosus (AF) injury plays a critical role in intervertebral disc degeneration (IVDD), with oxidative stress and extracellular matrix (ECM) imbalance being major pathogenic factors. However, effective repair methods are limited. In this study, an injectable photothermal hydrogel, Mn 3 O 4 @ChS-HA, composed of dopamine-grafted oxidized chondroitin sulfate (dop-OChS), adipic dihydrazide-modified hyaluronic acid (ADH-HA), and Mn 3 O 4 nanoparticles is constructed to repair AF damage. The Mn 3 O 4 @ChS-HA mimics the native intervertebral disc environment, offering excellent mechanical properties and strong adhesion to the AF defect site, while enabling long-term retention of Mn 3 O 4 nanoparticles. Mn 3 O 4 nanoparticles exhibit catalytic properties similar to those of superoxide dismutase, catalase, and glutathione peroxidase, efficiently scavenging reactive oxygen species and modulating ECM metabolism. In vitro and in vivo studies demonstrate that Mn 3 O 4 @ChS-HA significantly inhibits apoptosis, delays cell senescence, reduces inflammation, and promotes autophagy, facilitating AF repair. The hydrogel also restores disc height and maintained ECM integrity in a rat model of AF injury. Mild photothermal therapy (MPTT) further enhances these effects, supporting tissue regeneration and delaying the progression of IVDD. The MPTT-nanozyme-hydrogel system, Mn 3 O 4 @ChS-HA, exhibits various biological functions by regulating redox homeostasis and promoting tissue repair, highlighting the potential of this approach as a promising strategy for IVDD treatment.

CAS / MDL: 112-80-1 2592-95-2
研究领域: 生物医学工程 · 材料科学 · 骨科
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COMPOSITES PART B-ENGINEERING · 2022 · IF 11.322

Sustained gene delivery from inflammation-responsive anti-inflammatory hydrogels promotes extracellular matrix metabolism balance in degenerative nucleus pulposus

Yu Wang,Mingyan Deng,Ye Wu,Cheng Hu,Bo Zhang,Chuan Guo,Haoyang Song,Qingquan Kong,Yunbing Wang

The progression of intervertebral disc degeneration (IDD) is characterized by an initial chronic local inflammatory response and ultimately leads to unbalanced anabolic/catabolic activity within the nucleus pulposus (NP). Injectable inflammation-responsive hydrogels have great potential in treating IDD through on-demand local drug delivery. Here, we designed an injectable inflammation-responsive gelatin-based hydrogel for local and sustained delivery of the naturally extracted anti-inflammatory curcumin and a cholesterol-modified miRNA-21 inhibitor (Antagomir-21) to treat IDD. We successfully demonstrated the robust biocompatibility and ideal inflammation-responsive and on-demand drug release properties of hydrogels, as well as the great potential of IDD regeneration. This work proposes the novel inflammation-responsive hydrogel-based curcumin and miRNA delivery systems for the treatment of IDD.

CAS / MDL: 9000-70-8
研究领域: 生物医学工程 · 药学 · 再生医学
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Frontiers in Bioengineering and Biotechnology · 2023 · IF 5.7

Cerium oxide nanoparticles protect against chondrocytes and cartilage explants from oxidative stress via Nrf2/HO-1 pathway in temporomandibular joint osteoarthritis

Xiong Liping,Bao Han,Li Size,Gu Deao,Li Yuyang,Yin Qianwen,Li Wen,Miao Leiying,Liu Chao

Oxidative stress is closely linked to the etiology of temporomandibular joint osteoarthritis. (TMJ-OA) and is an important therapeutic target. Cerium oxide nanoparticles (CNPs) have been broadly studied owing to their powerful antioxidant properties and potential preventive and therapeutic effects against chronic diseases. The current study was designed to explore the protective effects of CNPs on the progression of TMJ-OA and their potential mechanisms. We detected the ability of CNPs to eliminate reactive oxygen species (ROS) in chondrocytes. Moreover, their protective effects on chondrocytes were detected in the level of gene and protein. Furthermore, TUNEL assay, histology and safranin O-fast green staining were used to detect the beneficial effects of CNPs on cartilage explants. The mechanism of CNPs, protecting condylar cartilage by reducing inflammation, was further explored by knocking down the Nuclear factor-erythroid 2-related factor (Nrf2) gene. CNPs could reduce the ROS levels in chondrocytes and cartilage explants and reverse the IL-1β-induced imbalance of cartilage matrix metabolism and apoptosis. The protective effects of CNPs on cartilage were lost after key antioxidant factors including Nrf2 and heme-oxygenase 1(HO-1) were significantly reduced. In conclusion, this study demonstrated for the first time that activating the Nrf2/HO-1 signaling pathway by CNPs might have therapeutic potential for TMJ-OA.

CAS / MDL: 107-21-1
研究领域: 骨科 · 纳米技术 · 药理学 · 细胞生物学 · 分子生物学
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JOR Spine · 2024 ·Vol. 7 ·期 1 ·e1316 · IF 3.4

Dynamics of N6-methyladenosine modification during aging and their potential roles in the degeneration of intervertebral disc

Libangxi Liu,Hong Sun,Yang Zhang,Chang Liu,Yong Zhuang,Miao Liu,Xuezheng Ai,Dan Long,Bo Huang,Changqing Li,Yue Zhou,Shiwu Dong,Chencheng Feng

Background The N6-methyladenosine (m6A) dynamics in the progression of intervertebral disc (IVD) aging remain largely unknown. This study aimed to explore the distribution and pattern of m 6 A modification in nucleus pulpous (NP) tissues of rats at different ages. Methods Histological staining and MRI were performed to evaluate the degeneration of IVD. The expression of m6A modifiers was analyzed using qRT-PCR and western blot. Subsequently, methylated RNA immunoprecipitation next generation sequencing and RNA-seq were conducted to identify differences in m6A methylome and transcriptome of NP tissues. Results Compared to 2-month-old rats, we found significant changes in the global m6A level and the expression of Mettl3 and FTO in NP tissues from 20-month-old rats. During the progression of NP aging, there were 1126 persistently differentially m6A peaks within 931 genes, and 51 persistently differentially expressed genes. GO and KEGG analyses showed that these m6A peaks and m6A modified genes were mainly engaged in the biological processes and pathways of intervertebral disc degermation (IDD), such as extracellular matrix metabolism, angiogenesis, inflammatory response, mTOR and AMPK signaling pathways. Meanwhile, conjoint analyses and Venn diagram revealed a total of 405 aging related genes contained significant methylation and expression levels in 20-month-old rats in contrast to 2-month-old and 10-month-old rats. Moreover, it was found that four aging related genes with hypermethylated modification including BUB1, CA12, Adamts1, and Adamts4 depicted differentially expressed at protein level, of which BUB1 and CA12 were decreased, while Adamts1 and Adamts4 were increased during the progression of NP aging. Conclusion Collectively, this study elucidated the distribution and pattern of m6A modification during the aging of IVD. Furthermore, the m6A modified genes were involved in the IDD related biological processes and pathways. These findings may provide novel insights into the mechanisms and therapies of IDD from the perspective of aging.

CAS / MDL:
研究领域: 分子生物学 · 衰老研究 · 骨科 · 表观遗传学
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