Bioengineering-Basel
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2024
·Vol. 11
·期 11
·1066
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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
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产品关联
DOI
PubMed
高影响因子
Stem Cells International
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2019
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IF 3.902
Kaishun Xia,Jian Zhu,Jianming Hua,Zhe Gong,Chao Yu,Xiaopeng Zhou,Jingkai Wang,Xianpeng Huang,Wei Yu,Liming Li,Jianqing Gao,Qixin Chen,Fangcai Li,Chengzhen Liang
Background. Cell replacement therapy is an attractive alternative for treating degenerated intervertebral discs (IVDs), which are related to the reduction of nucleus pulposus-like cells (NP-lCs) and the loss of the extracellular matrix. Induced pluripotent stem cells (iPSCs) which resemble embryonic stem cells are considered to be a potential resource for restoring NP-lCs and disc homeostasis. Here, we proposed an efficient two-step differentiation protocol of human iPSCs into NP-lCs and continuously tested their in vivo ability to regenerate IVDs. Methods. A polymeric gelatin microsphere (GM) was generated for sustained release of growth and differentiation factor-5 (GDF-5) and as a cell delivery vehicle of NP-lCs. By injecting NP-lC-seeded GDF-5-loaded GMs into the rat coccygeal intervertebral discs, the disc height and water content were examined with the molybdenum target radiographic imaging test and magnetic resonance imaging examination. Histology and immunohistochemistry results were shown with H&E, S-O-Fast Green, and immunohistochemistry staining. Results. We demonstrated that the injection of NP-lC-seeded GDF-5-loaded GMs could reverse IDD in a rat model. The imaging examination indicated that disc height recovered and water content increased. Histology and immunohistochemistry results indicated that the NP cells as well as their extracellular matrix were partially restored. Conclusions. The results suggest that NP-lC-seeded GDF-5-loaded GMs could partially regenerate degenerated intervertebral discs after transplantation into rat coccygeal intervertebral discs. Our study will help develop a promising method of stem cell-based therapy for IDD.
研究领域:
干细胞生物学
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组织工程
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再生医学
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骨科
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Junxian Hu,Yibo Zhu,Xiaoxiao Li,Zeyu Pang,Xiangwei Li,Huilin Zhang,Yiyang Wang,Pei Li,Qiang Zhou
Medical and conservative treatments for intervertebral disc degeneration (IDD) primarily focus on alleviating symptoms. However, effective curative therapies that promote disc regeneration remain lacking. Recent advancements in disc repair materials offer a potential solution, but identifying effective cytokines for regeneration and developing efficient drug delivery systems are crucial for success. This study demonstrated a negative correlation between AQP3 expression levels and the extent of disc degeneration induced by mechanical overload, as evidenced in both in vivo and in vitro models, suggesting that AQP3 is a key regulator of intervertebral disc (IVD) homeostasis. Moreover, the overexpression of AQP3 or exogenous AQP3 protein significantly repaired degenerated IVDs. As a membrane protein, exogenous AQP3 is challenging for cells to recognize and internalize. To address this issue, we designed liposomes to encapsulate AQP3 and incorporated them into GelMA (AQP3-lipo@GelMA) for targeted repair of IDD resulting from high mechanical pressure. The encapsulation of AQP3 in liposomes improved cellular recognition and uptake, thereby enhancing its functionality at the cell membrane. Additionally, AQP3 within this material inhibited the binding of integrins to sialic acid-binding proteins (IBSP), which subsequently reduced the expression of the downstream integrin αVβ3. This cascade effect indirectly activated the AKT pathway, promoting the survival of NP cells. In vivo experiments, we found that AQP3-lipo@GelMA had an efficient function of repairing degenerated intervertebral disc. This study introduced AQP3-lipo@GelMA as a promising material for clinical applications in IVD repair.
研究领域:
再生医学
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骨科
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生物材料科学
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分子生物学
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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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Hao Liu,Xin Tian,Chenyang Jin,Yangfeng Li,Xuesong Zhu,Ming Pei,Tao Liu,Huilin Yang,Yong Xu,Fan He
Nucleus pulposus (NP) discectomy is a clinical procedure for the treatment of late-stage intervertebral disc (IVD) degeneration; however, it is associated with the potential for serious complications. The reconstruction of the NP tissue presents challenges due to its avascular structure and prolonged compression within the IVD. In this study, we have developed a novel biomimetic hydrogel microsphere composed of gelatin methacryloyl (GelMA) and fucoidan, a polysaccharide derived from marine brown seaweed, to mimic the extracellular matrix (ECM) of the native NP. The GelMA and fucoidan (GelMA@FD) hydrogel microspheres demonstrate favorable cytocompatibility and significantly enhance the synthesis of matrix components in nucleus pulposus cells (NPCs), including aggrecan and type II collagen. Transcriptome sequencing analysis demonstrates a correlation between the augmentation of matrix synthesis and the enrichment of genes and pathways related to mitochondrial function. Subsequent molecular investigations provide evidence that NPCs cultured on GelMA@FD exhibit enhanced mitochondrial functions, including elevated adenosine triphosphate production and respiratory chain factor expression, alongside a reduction in mitochondrial reactive oxygen species. When implantated into rat lumbar IVDs that have undergone discectomy, the incorporation of NPCs within GelMA@FD hydrogel microspheres facilitates the regeneration of the NP and reinstates its structural and biomechanical properties. This is substantiated by the observed augmentation in IVD disc height and water content within the NP compartment. Collectively, these results demonstrate the potential of employing cell-laden GelMA@FD hydrogel microspheres as a promising strategy for NP regeneration in degenerated IVDs.
研究领域:
生物材料
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组织工程
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再生医学
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骨科
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
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2024
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IF 9.4
Yan Ju,Shiyuan Ma,Meimei Fu,Min Wu,Yue Li,Yue Wang,Meihan Tao,Zhihui Lu,Jinshan Guo
Discectomy is the surgical standard of care to relieve low back pain caused by intervertebral disc (IVD) herniation. However, there remains annulus fibrosus (AF) defect and nucleus pulposus (NP) degeneration, which often result in recurrent herniation (re-herniation). Herein, we develop a polyphenol-modified waterborne polyurethane bioadhesives (PPU-glues) to promote therapy prognosis after discectomy. Being composed of tannic acid (TA) mixed cationic waterborne polyurethane nanodispersions (TA/WPU + ) and curcumin (Cur) embedded anionic waterborne polyurethane nanodispersions (Cur-WPU - ), PPU-glue gels rapidly (<10 s) and exhibits low swelling ratios, tunable degradation rates and good biocompatibility. Due to the application of an adhesion strategy combing English ivy mechanism and particle packing theory, PPU-glue also shows considerable lap shear strength against wet porcine skin (≈58 kPa) and burst pressure (≈26 kPa). The mismatched particle sizes and the opposite charges of TA/WPU + and Cur-WPU - in PPU-glue bring electrostatic interaction and enhance particle packing density. PPU-glue possesses superior reactive oxygen species (ROS)-scavenging capacity derived from polyphenols. PPU-glue can regulate extracellular matrix (ECM) metabolism in degenerated NP cells, and it can promote therapy biologically and mechanically in degenerated rat caudal discs. In summary, this study highlights the therapeutic approach that combines AF seal and NP augmentation, and PPU-glue holds great application potentials for post discectomy therapy. Statement of Significance Currently, there is no established method for the therapy of annulus fibrosus (AF) defect and nucleus pulposus (NP) degeneration after discectomy. Herein, we developed a polyphenol-modified biomimetic polyurethane bioadhesives (PPU-glue) with strong adhesive strength and superior bioactive property. The adhesion strategy that combined a particle packing theory and an English ivy mechanism was firstly applied to the intervertebral disc repair field, which benefited AF seal. The modified method of incorporating polyphenols was utilized to confer with ROS-scavenging capacity, ECM metabolism regulation ability and anti-inflammatory property, which promoted NP augmentation. Thus, PPU-glue attained the synergy effect for post discectomy therapy, and the design principle could be universally expanded to the bioadhesives for other surgical uses.
研究领域:
生物医学工程
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组织工程
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骨科
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材料科学
✓ 已验证
DOI
高影响因子
Drug Design Development and Therapy
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2022
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IF 4.319
Huan Wang,Yifan Ding,Wei Zhang,Kang Wei,Yaping Pei,Chenming Zou,Chong Zhang,Jiahui Ding,Huang Fang,Songwei Tan
Purpose Intervertebral disc degeneration (IVDD) is the main cause of modern low back pain, leading to high societal economic costs. To find an effective medical treatment for this disease, oxymatrine liposomes (OMT-LIP) were prepared with the pH-gradient method.Materials and Methods Nucleus pulposus (NP) cells from Sprague–Dawley rats were used for the cell experiments. Kunming mice were used for in vivo imaging. LIP were employed to deliver OMT, and the particle size, ζ-potential, morphology, in vitro stability and in vitro release characteristics were evaluated. The OMT-LIP targeting effect was measured by in vivo imaging. Cell Counting Kit-8 assays were used to detect the cytotoxicity of OMT and OMT-LIP on NP cells. Therapeutic efficacy was measured by Western blot, real-time quantitative polymerase chain reaction, and apoptosis assays. Radiologic analysis was performed to evaluate the therapeutic effects in vivo.Results Orthogonal test results revealed that the mass ratio of egg yolk phosphatidylcholine to cholesterol was the key factor to effectively trap OMT in LIP. Optimal OMT-LIP showed multivesicular structure with entrapment efficiency of 73.4 ± 4.1%, particle size of 178.1 ± 2.9 nm, and ζ-potential of –13.30 ± 2.34 mV. OMT-LIP manifested excellent stability in vitro and presented significantly longer sustained release compared to OMT solution in phosphate-buffered saline (pH 7.4). OMT-LIP conspicuously increased OMT accumulation in the degenerative disc, attenuated NP cell apoptosis, reduced the expression of matrix metalloproteinases 3/9 and interleukin-6, and decreased degradation of type II collagen. In in vivo study, X-ray demonstrated that OMT-LIP inhibited IVDD.Conclusion OMT-LIP may be a useful treatment to alleviate disc inflammation and IVDD.
研究领域:
药理学
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骨科
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生物医学工程
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 24
·期 1
·390
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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
Journal of Orthopaedic Translation
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2025
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IF 7.8
Huan Wang,Moyan Li,Jiaojiao Yang,Zhao Liu,Shijie Shi,Dachuan Liu,Youzhi Hong,Hongjian Liu,Songfeng Chen,Jiyao Li,Song Chen,Bin Li
Background Intervertebral disc (IVD) herniation is a major cause of low back pain and disability, with microdiscectomy being the standard surgical treatment. However, microdiscectomy fails to address annulus fibrosus (AF) defects, increasing the risk of recurrent herniation. Current therapeutic strategies for this condition remain limited in efficacy. The lack of repair following injury and unresolved inflammation can further damage the IVD function, ultimately leading to irreversible IVD degeneration. Therefore, the development of an AF adhesive capable of both mechanically stabilizing annular fissures and enabling localized anti-inflammatory drug delivery emerges as a promising strategy to address this clinical challenge. Methods The developed AF adhesive system, designated as STIG, is formulated from silk fibroin, tannic acid, ibuprofen, and guanidine hydrochloride (GuCl). A comprehensive evaluation is conducted on STIG, encompassing its microstructure, composition, injectability, tissue adhesion, rheological properties, and biocompatibility. To assess anti-inflammatory efficacy, an in vitro inflammatory microenvironment is established via lipopolysaccharide (LPS)-stimulated AF cells. For in vivo validation, a rat model of IVD degeneration is surgically induced through puncturing the AF to simulate nucleus pulposus (NP) herniation. This experimental framework enables evaluation of STIG's ability to prevent NP protrusion, modulate inflammatory responses, and delay IVD degeneration. Results In the STIG system, GuCl serves the role of a hydrogen bond disruptor, facilitating its release into bodily fluids, which in turn allows for the reformation of hydrogen bonds. This property endows STIG with the ability to transition from an injectable, low-stiffness state to a high-stiffness adhesive gel upon contact with water. The inclusion of ibuprofen in the adhesive effectively curbs the production of inflammatory mediators and the breakdown of extracellular matrix constituents. In a rat tail model, STIG effectively preserves the NP water content, maintains the disc height index, and safeguards the structural integrity of the IVD post-surgery. Conclusion These findings highlight STIG's potential as a promising therapeutic solution for sealing AF fissures and preventing IVD degeneration. The translational potential of this article STIG shows significant clinical potential in spinal surgery. It offers a novel approach to reduce the recurrence rate post-microdiscectomy and improving long-term patient outcomes.
研究领域:
生物医学工程
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材料科学
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骨科手术
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再生医学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-14
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IF 10.6
Bu Wenzhen,Shi Yu,Huang Xueping,Wu Shang,Jiang Letao,Pan Chun,Li Dandan,Xu Zhuobin,Wang Huihui,Chen Hao,Du Jianwei
The senescence of nucleus pulposus (NP) cells (NPCs), which is induced by the anomalous accumulation of reactive oxygen species (ROS), is a major cause of intervertebral disc degeneration (IVDD). In this research, glutathione-doped carbon dots (GSH-CDs), which are novel carbon dot antioxidant nanozymes, were successfully constructed to remove large amounts of ROS for the maintenance of NP tissue at the physical redox level. After significantly scavenging endogenous ROS via exerting antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity, GSH-CDs with good biocompatibility have been demonstrated to effectively improve mitochondrial dysfunction and rescue NPCs from senescence, catabolism, and inflammatory factors in vivo and in vitro. In vivo imaging data and histomorphological indicators, such as the disc height index (DHI) and Pfirrmann grade, demonstrated prominent improvements in the progression of IVDD after the topical application of GSH-CDs. In summary, this study investigated the GSH-CDs nanozyme, which possesses excellent potential to inhibit the senescence of NPCs with mitochondrial lesions induced by the excessive accumulation of ROS and improve the progression of IVDD, providing potential therapeutic options for clinical treatment.Graphical Abstract
研究领域:
生物医学工程
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纳米技术
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骨科
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细胞生物学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
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2025
·Vol. 16
·期 1
·1-22
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IF 15.7
Wang Wenkai,Cheng Zhuo,Yu Miao,Liu Ke,Duan Hongli,Zhang Yang,Huang Xinle,Li Menghuan,Li Changqing,Hu Yan,Luo Zhong,Liu Minghan
Discectomy-induced ferroptosis of nucleus pulposus cells (NPCs) contributes to postoperative lumbar disc herniation (LDH) recurrence and intervertebral disc degeneration (IDD). We discover that nucleus pulposus progenitor cells (NPPCs) could imprint ferroptosis resistance into NPCs through exosome-dependent intercellular transmission of miR-221-3p. Based on these findings, we first develop synthetically-tailored NPPC-derived exosomes with enhanced miR-221-3p expression and NPC uptake capacity, which are integrated into an injectable hydrogel based on extracellular matrix (ECM) analogues. The ECM-mimetic hydrogel (HACS) serves as a biomimetic filler for the post-operative care of herniated discs, which could be facilely injected into the discectomy-established nucleus pulposus (NP) cavity for localized treatment. HACS-mediated in-situ exosome release in the NP cavity enables marked ferroptosis inhibition in NPCs that not only prevents LDH recurrence but also reverses the IDD symptoms, leading to robust restoration of NP structure and functions. In summary, this study offers a promising approach for treating disc herniation.
研究领域:
医学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2025
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IF 5.7
Jing Wang,Leizhen Huang,Tao Guo,Zheng Liu,Huilun Xu,Hao Yang,Limin Liu,Ganjun Feng,Li Zhang
Discectomy is the most commonly used surgery in treating herniation-induced nerve compression, but it often destroys the structural integrity and leaves a defect in the intervertebral disc (IVD), leading to re-herniation risk. Considering that electric signals play a crucial role in tissue regeneration, a dual-electroactive scaffold was fabricated to promote the repair effect of the discectomy-left IVD defect. An electroconductive scaffold (G10) was 3D-printed firstly by doping graphene to form electro-osmotic networks in a polycaprolactone (PCL) matrix, then tetragonal barium titanate (T-BT) doped polyvinylidene fluoride (PVDF) fibrous membranes (B5) with piezoelectricity were electrospun on both the upper and lower surfaces of G10 to obtain a sandwich-structured scaffold (G10B5) with both piezoelectric and electroconductive activities. The in vitro experimental results confirmed that the dual-electroactive G10B5 scaffold could well mimic the electroconductive properties of natural IVDs and harvest ambient mechanical energy to produce electrical stimuli, thus recruiting surrounding stem cells. Following implantation in defective IVDs of rats, the dual-electroactive scaffolds could effectively decrease the loss of cells and extracellular matrix (ECM) and maintain the composite cartilage structure of IVDs. The dual-electroactive scaffold with a sandwich structure is proposed here to provide a novel strategy for treating the IVD defects after discectomy and broaden the application of electroactive biomaterials in tissue regeneration.
研究领域:
生物医学工程
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组织工程
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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