Bioengineering-Basel
·
2024
·Vol. 11
·期 11
·1066
·
IF 3.8
Qianfu Zhang,Zhixuan Li,Sihan Zhou,Ji Li
Intervertebral disc degeneration (IVDD) is a significant cause of chronic pain and disability, necessitating innovative therapeutic strategies. This study investigates the combined effect of a novel siCOL1A2-encapsulated hydrogel and acupuncture on IVDD in a rat model. We developed a hydrogel system, siCOL1A2-encapsulated G5-PBA hydrogel (siCOL1A2@G5-PBA@Gel), designed for sustained siRNA delivery to the degenerated discs and assessed its therapeutic efficacy alongside acupuncture treatment. Key inflammatory genes were identified through RNA-seq analysis, with COL1A2 highlighted as a crucial regulator of inflammatory responses in IVDD. Our in vivo experiments involved treating rats with hydrogel alone, acupuncture alone, and combining both. The treatments were evaluated through behavioral pain assessments, imaging techniques (X-ray and MRI), and histological analyses. Results indicated that the combination therapy significantly alleviated pain, reduced inflammation, and promoted disc regeneration more effectively than individual treatments. The hydrogel proved biocompatible and facilitated targeted gene silencing, while acupuncture enhanced therapeutic outcomes by improving local blood circulation and modulating inflammatory responses. These findings suggest that integrating siCOL1A2 hydrogel with acupuncture offers a promising approach to treating IVDD.
研究领域:
医学
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生物技术
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 10
·3629-3644
·
IF 6.6
Huitong Luo,Zetao Wang,Zhichao He,Zemin Ling,Hao Wang,Jiayi Zhu,Jingjun Nie,Dafu Chen,Qi Feng,Xiaodong Cao
Overactive inflammatory cascade accompanied by oxidative stress in the nucleus pulposus exacerbates intervertebral disc degeneration (IVDD). Hydrogels have been demonstrated to be promising in treating IVDD, yet they remain less efficacious in the case of anti-inflammation associated with antioxidation. In this study, we designed an injectable self-antioxidant hydrogel (HA/CS) with enhanced inflammation inhibitory performance for delivering chondroitin sulfate (CS) with well-documented anti-inflammatory property to treat IVDD. The hydrogel was rapidly formed via dynamic boronate ester bonding between furan/phenylboronic acid and furan/dopamine-modified hyaluronic acid (HA), and mechanically enhanced by Diels–Alder reaction-induced secondary crosslinking, partial dopamine groups of which contribute to grafting phenylboronic acid-modified CS (CS-PBA). This hydrogel exhibits favorable injectability, mechanical property, and pH-responsive delivery behavior. The dopamine moiety endows the hydrogel with efficient antioxidative property. By sustained delivery of CS, the HA/CS hydrogel is well competent to inhibit inflammatory cytokine expression and maintain anabolic/catabolic balance in an inflammation-simulated environment. Most importantly, the HA/CS hydrogel significantly ameliorates degeneration in a puncture-induced IVDD rat model. The self-antioxidant HA/CS hydrogel designed in this work may serve as a novel and promising therapeutic platform for IVDD.
研究领域:
生物材料
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组织工程
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骨科
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炎症
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氧化应激
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Jiaoxiang Chen,Xin Gan,Shenkai Su,Sizhe Jiao,Zailing Gong,Ziqiang Liu,Xiaopei Wu,Jun Jiang,Jiaming Zhang,Junlai Wan
Intervertebral disc degeneration (IVDD) is a multifaceted and complex condition primarily driven by excessive inflammation, degradation of the extracellular matrix (ECM), and dysfunction of nucleus pulposus cells (NPCs). Despite extensive exploration of various therapeutic agents targeting IVDD, their efficacy remains disappointingly limited. This study underscores the efficacy of ginkgetin (GK), a natural bioflavonoid with potent anti-inflammatory properties, in mitigating inflammation as well as ECM degradation and NPC dysfunction triggered by interleukin-1β (IL-1β). However, GK alone cannot fully address the persistent obstruction in autophagic flux induced by IL-1β. To overcome this limitation, an innovative MMP13-responsive nanoplatform was developed, orchestrating the sequential delivery of GK and rapamycin (RA), targeting distinct phases of IVDD progression. In this design, GK is progressively released from exosomes during the initial phase, while RA is released from mesoporous silica nanoparticles during the mid-phase to enhance autophagic flux. This staged release approach leverages the strengths of both agents, addressing inflammation and restoring autophagy more effectively. In vivo experiments confirmed the substantial therapeutic benefits of this staggered delivery strategy in IVDD. The engineered MMP13-responsive nanoplatform represents a significant advancement in controlled, sequential drug delivery systems, offering a promising therapeutic avenue to effectively regulate inflammation and autophagy, thereby ameliorating IVDD.
研究领域:
医学
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生物材料学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 24
·期 1
·390
·
IF 6.208
Haozhe Cheng,Qian Guo,Hongjian Zhao,Kun Liu,Honglei Kang,Fang Gao,Jianfeng Guo,Xi Yuan,Shuang Hu,Feng Li,Qin Yang,Zhong Fang
Due to the unique physical characteristics of intervertebral disc degeneration (IVDD) and the pathological microenvironment that it creates, including inflammation and oxidative stress, effective self-repair is impossible. During the process of intervertebral disc degeneration, there is an increase in the infiltration of M1 macrophages and the secretion of proinflammatory cytokines. Here, we designed a novel injectable composite hydrogel scaffold: an oligo [poly (ethylene glycol) fumarate]/sodium methacrylate (OPF/SMA) hydrogel scaffold loaded with dual-drug/sustained-release PLGA microspheres containing IL-4 (IL-4-PLGA) and kartogenin (KGN-PLGA). This scaffold exhibited good mechanical properties and low immunogenicity while also promoting the sustained release of drugs. By virtue of the PLGA microspheres loaded with IL-4 (IL-4-PLGA), the composite hydrogel scaffold induced macrophages to transition from the M1 phenotype into the M2 phenotype during the early induced phase and simultaneously exhibited a continuous anti-inflammatory effect through the PLGA microspheres loaded with kartogenin (KGN-PLGA). Furthermore, we investigated the mechanisms underlying the immunomodulatory and anti-inflammatory effects of the composite hydrogel scaffold. We found that the scaffold promoted cell proliferation and improved cell viability in vitro. While ensuring mechanical strength, this composite hydrogel scaffold regulated the local inflammatory microenvironment and continuously repaired tissue in the nucleus pulposus via the sequential release of drugs in vivo. When degenerative intervertebral discs in a rat model were injected with the scaffold, there was an increase in the proportion of M2 macrophages in the inflammatory environment and higher expression levels of type II collagen and aggrecan; this was accompanied by reduced levels of MMP13 expression, thus exhibiting long-term anti-inflammatory effects. Our research provides a new strategy for promoting intervertebral disc tissue regeneration and a range of other inflammatory diseases.Keywords:drug delivery;hydrogel;intervertebral disc degeneration;immune regulation;kartogenin
研究领域:
生物医学工程
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组织工程
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药剂学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Yu Wang,Ye Wu,Bo Zhang,Cheng Zheng,Cheng Hu,Chuan Guo,Qingquan Kong,Yunbing Wang
Intervertebral disc degeneration (IDD) progresses due to local inflammatory response, gradually unbalanced anabolic/catabolic activity, and progressive functional impairment within the nucleus pulposus. Antagomir-21, a cholesterol-modified miRNA-21 inhibitor, has potential extracellular matrix (ECM) regenerative ability , but its application for IDD is limited by inadequate local delivery systems. An injectable hydrogel gene delivery system encapsulating a modified tannic acid nanoparticles (TA NPs) vector was engineered for on-demand and sustained delivery of antagomir-21 into the nucleus pulposus. After nucleus pulposus cell uptake, antagomir-21 was released from TA NPs and regulated the ECM metabolic balance by inhibiting the MAPK/ERK signaling pathway . TA NPs scavenged intracellular ROS and reduced inflammation by downregulating TNF-α expression. In vivo , synergistic anti-inflammatory effects and ECM regeneration effectively promoted therapeutic efficacy against IDD. This hydrogel gene delivery system represents a creative, promising strategy for IDD repair.
研究领域:
生物医学工程
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骨科
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基因治疗
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纳米技术
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 9
·3877
·
IF 13.3
Yueyang Li,Yu Zhai,Tianling Wang,Siya Wang,Yu Tian,Zhiqun Bian,Yang Zhang,Chao Zhang,Minghan Liu,Changqing Li
Rationale: Nucleus pulposus (NP) fibrosis is a contributing factor to intervertebral disc degeneration (IVDD), which lacks an effective treatment. This study focuses on elucidating the role and mechanisms of the TGF-β signaling repressor SKI in NP fibrosis and exploring its therapeutic potential. Methods: Single-cell RNA sequencing (scRNA-seq) was used to investigate fibrotic nucleus pulposus cell (NPC) subsets and assess TGF-β signaling activation. Two recombinant plasmids encoding single-chain variable fragments (scFvs) targeting the fibrotic NPC marker FAP and SKI mRNA were co-transfected into HEK-293T cells to yield functionalized exosomes (EX ski+scFv ). The addition of EX ski+scFv to a gelatin/oxidized sodium alginate hydrogel produced a pH-responsive exosome/hydrogel system named Gel@EX ski+scFv . The therapeutic effects and underlying mechanism of Gel@EX ski+scFv were evaluated by RNA sequencing, molecular docking and coimmunoprecipitation. Results: A fibrotic NPC subset was characterized by elevated FAP and diminished SKI expression, along with activation of the TGF-β signaling pathway. SKI overexpression reduced fibrosis in TGF-β-treated NPCs. EX ski+scFv successfully delivered SKI mRNA to FAP-expressing fibrotic NPCs. Gel@EX ski+scFv possessed good mechanical properties, degradability, injectability, and biocompatibility. Gel@EX ski+scFv effectively alleviated NP fibrosis and IVDD in rats. RNA sequencing, molecular docking and coimmunoprecipitation revealed that SKI could interact with FOXO3 to suppress the TGF-β signaling pathway. Conclusion: This study elucidates the mechanism by which SKI -mediated TGF-β signaling inhibition alleviates NP fibrosis. The development of the Gel@EX ski+scFv system for the targeted delivery of SKI mRNA offers a promising therapeutic strategy to alleviate NP fibrosis and IVDD in the future.
研究领域:
生物医学
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分子生物学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-25
·
IF 12.6
Zhang Xiaoyu,Guo Qianping,Fang Jiawei,Cheng Qi,Zhu Zhuang,Yu Qifan,Wang Huan,Hong Youzhi,Liu Chengyuan,Yang Huilin,Zhu Caihong,Li Bin,Ni Li
Nucleus pulposus cells (NPCs) undergo metabolic disorders and matrix pathological remodeling under the influence of various adverse factors during intervertebral disc degeneration (IVDD), whereas post-translational modifications (PTMs) can confer cells with the capacity to respond quickly and adapt to complex environmental changes. Here, SIRT1 protein, a key regulator within PTMs framework, was applied against the hostile degenerative microenvironment. Then, it was sequentially assembled with SOX9-expressing plasmid, an essential transcription factor to promote extracellular matrix (ECM) biosynthesis, onto a phenylboronic acid-functionalized G5-dendrimer to construct a multifunctional nanoplatform for IVDD therapy. In vitro, the nanoplatforms showed antioxidant capacity, and the ability to restore mitochondrial homeostasis and normal ECM metabolism, as well as to maintain cellular phenotypes. RNA sequencing suggested that inhibition of the Nod-like receptor signaling might be the mechanism behind their therapeutic effects. The nanoplatforms were then wrapped in a designed dynamic hydrogel, not only prolonging the retention time of the loaded cargoes, but also well maintaining the disc structure, height, and water content in vivo. Overall, this study presents a convenient assembled strategy to inhibit the multiple adverse factors, and hold promise for the IVDD treatment. Graphical abstract
研究领域:
医学
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生物材料学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Sunlong Li,Siyu Hu,Yifeng Shi,Yeheng Huang,Yuli Chen,Yan Chen,Fengyu Zhang,Zhan Gao,Shuqing Jin,Qiwei Zhou,Shu Yang,Haibo Liang,Lianggao Yu,Shuhao Zhang,Chongan Huang,Chenglong Xie,Zaher Meftah,Aimin Wu,Xiaolei Zhang,Xiangyang Wang
Ferroptosis is a major contributor to intervertebral disc degeneration (IVDD) and represents a promising therapeutic target; however, effective medications that specifically target ferroptosis are still lacking. Consequently, strategies aimed at suppressing the expression of ferroptosis-related genes, such as small interfering RNA (siRNA) targeting activating transcription factor 3 (ATF3), appear to be a feasible therapeutic approach for IVDD. Zeolitic imidazolate framework-8 (ZIF-8) exhibits exceptionally high binding affinity for nucleic acids, including siRNA. Nevertheless, its practical application is hindered by challenges such as limited siRNA encapsulation and potential toxicity arising from Zn 2 ⁺ ion release during degradation. In the current study, a novel siRNA delivery system is designed with low toxicity, high encapsulation efficiency, and sustained release by hybridizing classical ZIF-8 with histidine (H-ZIF-8) through defect engineering. In vitro functional studies demonstrated that H-ZIF-8 significantly enhances the delivery efficiency of siATF3 in nucleus pulposus cells (NPCs), and effectively suppresses ferroptosis and extracellular matrix (ECM) degradation. Furthermore, the incorporation of histidine into ZIF-8 may improve its biocompatibility by reducing the proportion of Zn 2 ⁺ ions present. In vivo, siATF3@H-ZIF-8 significantly inhibited ferroptosis and alleviated intervertebral disc degeneration (IVDD) in a rat model through sustaining ATF3 knockdown. This research suggests that histidine-modified ZIF-8 may serve as a novel system for siRNA delivery and an effective gene therapy method for diseases, including IVDD.
研究领域:
生物医学工程
·
基因治疗
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材料科学
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2024
·
IF 18
Juehan Wang,Yulin Jiang,Ce Zhu,Zheng Liu,Lin Qi,Hong Ding,Jing Wang,Yong Huang,Yubao Li,Yueming Song,Ganjun Feng,Li Zhang,Limin Liu
Previous studies have confirmed that intervertebral disc degeneration (IDD) is closely associated with inflammation-induced reactive oxygen species (ROS) and resultant cell mitochondrial membrane potential (MMP) decline. Clearance of ROS in an inflammatory environment is essential for breaking the vicious cycle of MMP decline. Additionally, re-energizing the mitochondria damaged in the inflammatory milieu to restore their function, is equally important. Herein, we proposed an interesting concept of mitochondrion-engine equipped with coolant, which enables first to “cool-down” the inflammatory environment, next to restore the MMP, finally to allow cells to regain normal energy metabolism through materials design. As such, we developed a multi-functional composite composed of a reactive oxygen species (ROS)-responsive sodium alginate/gelatin hydrogel infused into a rigid 3D-printed thermoplastic polyurethane (TPU) scaffold. The TPU scaffold was coated with conductive polypyrrole (PPy) to electrophoretically deposit l -arginine, which could upregulate the Mammalian target of rapamycin ( mTOR ) pathway, thus increasing MMP and energy metabolism to stimulate extracellular matrix synthesis for IVD repair. While the ROS-responsive hydrogel acting as the “mito-engine coolant” could scavenge the excessive ROS to create a favorable environment for IVD cells recovery. Demonstrated by in vitro and in vivo evaluations, the mito-engine system markedly promoted the proliferation and collagen synthesis of nucleus pulposus cells while enhancing the mitochondrial respiration and MMP under oxidative stress. Radiological and histological assessments in vivo revealed the efficacy of this system in IVD repair. This unique bioinspired design integrated biomaterial science with mitochondrial biology, presents a promising paradigm for IDD treatment.
研究领域:
生物材料科学
·
医学工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2025
·
IF 14.3
Huitong Luo,Zhipeng Sun,Zetao Wang,Wanqing Lun,Qi Feng,Dafu Chen,Xiaodong Cao
Effective treatment of intervertebral disc degeneration with biomaterials remains a challenge, owing to the difficulty in simultaneously overcoming oxidative stress and its associated cascades in the nucleus pulposus microenvironment, which includes cellular senescence, apoptosis, inflammation, and extracellular matrix (ECM) degradation. To address these issues, a multifunctional hydrogel (HG-QNT) loaded with transforming growth factor- β 1 (TGF- β 1) and quercetin-based nanoparticles (QUNPs) is developed through borate ester bonding and Schiff base reaction-induced crosslinking. Specifically, QUNPs fabricated via coordination and hydrophobic interactions endow the hydrogel with extraordinary antioxidative properties. Benefiting from the multi-dynamic crosslinking, the hydrogel achieves self-healing, mechanical stability, and pH-responsive release of QUNPs and TGF- β 1. The HG-QNT hydrogel is demonstrated to enhance the proliferation of encapsulated nucleus pulposus cells, thereby providing an ideal platform for cell transplantation. The cooperative antioxidation of QUNPs and the hydrogel carrier renders HG-QNT effective in mitigating oxidative stress, resulting in the suppression of cellular senescence, mitochondrial dysfunction, apoptosis, excessive inflammation, and abnormal catabolism. Afterwards, TGF- β 1 and QUNPs act in synergy with the hydrogel to restore the anabolic/catabolic balance by enhancing ECM synthesis. Overall, the strategy orchestrating multiple modulation by HG-QNT hydrogel shows great potential for application in intervertebral disc regeneration.
研究领域:
生物材料学
·
再生医学
·
组织工程
✓ 已验证
产品关联
DOI
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Yuan Xu,Jian He,Jun He
Purpose The treatment of intervertebral disc degeneration is limited, cyanidin can protect chondrocytes from degeneration. This research investigated the effect of cyanidin on human nucleus pulposus cells (HNPC) metabolism and its mechanism. Methods HNPC were treated with cyanidin, XAV-939 (inhibitor of Wnt/β-catenin signaling) and SKL2001 (activator of Wnt/β-catenin signaling), and pressurized at 1, 3, and 30 atm. Quantitative real-time PCR and Western blot were used to assess the expressions of matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), Collagen-II, Aggrecan , Wnt-3a and β-catenin in treated HNPC. Cell counting kit-8 was used to detect the HNPC cell viability . Radioisotope incorporation method was used to assess the proteoglycan synthesis rate of HNPC. The level of cell matrix was detected by toluidine blue staining. Results Proper hydrostatic pressure of 3 atm could elevate cell viability, proteoglycan synthesis and the level of cell matrix of HNPC, while high hydrostatic pressure of 30 atm reduced the above effects. Cyanidin and XAV-939 reversed the promoting effect of 30 atm pressure on Wnt/β-catenin signaling pathway and the inhibiting effect on cell viability, proteoglycan synthesis and the level of cell matrix. Subsequently, SKL2001 further reversed the function of cyanidin on HNPC. Conclusion Cyanidin attenuated the high hydrostatic pressure-induced degradation of cellular matrix of HNPC via blocking the Wnt/β-catenin signaling pathway. Our findings in this research provided a basis for in vitro experiment of cyanidin and a theoretical fundament on this disease.
研究领域:
骨科
·
细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF PATHOLOGY
·
2024
·
IF 4.7
Mingxiang Zou,Wenkang Chen,Jing Li,Xin Qi,Xiaobin Wang,Fubing Liu,Jiarui Hu,Qianshi Zhang
This study investigated the role of apoptosis signal-regulated kinase-1 ( ASK1 ) in intervertebral disc degeneration (IDD). The nucleus pulposus (NP) tissues of non-IDD and IDD patients were subjected to hematoxylin and eosin, Safranin O–fast green, and immunohistochemical staining. Quantitative real-time PCR was used to assess the ASK1 mRNA level within NP tissue samples and cells. The Cell Counting Kit-8 assay, senescence-associated β-galactosidase staining, and then flow cytometry were conducted, respectively, to assess the viability, senescence, and apoptosis of NP cells. The extracellular matrix–related factors were detected using Western blot analysis. Furthermore, the effect of ASK1 on the IDD rat model was evaluated through nuclear magnetic resonance imaging analysis, hematoxylin and eosin, Safranin O–fast green staining, and immunohistochemical staining. Finally, c-Jun N-terminal kinase (JNK) inhibitors were used to verify the effect of the JNK/p38 signaling on IDD. ASK1 mRNA and protein were up-regulated within NP tissue samples from the IDD group, IL-1β–stimulated NP cells, and IDD rats. ASK1 inhibition promoted cell viability and repressed the senescence and apoptosis of NP cells; promoted collagen II and aggrecan; inhibited matrix metalloproteinase 3, matrix metalloproteinase 9, a disintegrin and metalloproteinase with thrombospondin motifs 4, and a disintegrin and metalloproteinase with thrombospondin motifs 5 protein levels; and increased NP cells in rat intervertebral disc tissues. ASK1 overexpression exerted the opposite effects of ASK1 inhibition on NP cells. Additionally, JNK/p38 signaling suppression could reverse the ASK1 up-regulation–induced dysfunction. In conclusion, ASK1 facilitated the senescence and apoptosis of NP cells in promoting IDD progression, which may be mediated by the JNK/p38 pathway.
研究领域:
骨科
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）