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PHYTOMEDICINE · 2021 · IF 5.34

Avicularin suppresses cartilage extracellular matrix degradation and inflammation via TRAF6/MAPK activation

Zi-ling Zou,Ming-hui Sun,Wei-feng Yin,Lei Yang,Ling-yi Kong

Background Osteoarthritis (OA) is an intractable degenerative disease of the whole joint, which is characterized by synovitis inflammation, cartilage damage, and chronic pain. Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) performs an important role in OA. Purpose We aim to investigate avicularin to protect cartilage extracellular matrix degradation (ECM) and suppresses inflammation both in rat and human chondrocytes . Methods 5-Ethynyl-2′-deoxyuridine (EdU) staining, Quantitative real-time PCR, TRAF6 plasmid transfection, Western blot , Measurement of nitric oxide (NO), ROS detection and Immunofluorescence were utilized in vitro . micro-CT scanning, Safranin O-Fast Green, toluidine blue and immunohistochemistry staining were performed in vivo . Results In vitro , avicularin attenuates the degradation of ECM and inflammation, which could inhibit the activation of TRAF6/MAPK pathway via targeting TRAF6. Increased MMP3 and MMP13 expressions and decreased Aggrecan and Collagen Ⅱ levels were observed in anterior cruciate ligament transection (ACLT) induced osteoarthritic rats. Interestingly, intra-articular injection of avicularin attenuates this phenomenon. Conclusions Taken together, our results indicate that avicularin suppresses cartilage extracellular matrix degradation and inflammation via TRAF6/MAPK activation by targeting TRAF6. These observations identify TRAF6 as a relevant drug target, and avicularin may as a potential therapeutic agent in osteoarthritis.

CAS / MDL: 298-93-1
研究领域: 药理学 · 风湿病学 · 骨科 · 细胞生物学
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Biomaterials Science · 2023 ·Vol. 11 ·期 8 ·2877-2885 · IF 6.6

Extracellular matrix (ECM)-inspired high-strength gelatin-alginate based hydrogels for bone repair

Tengling Wu,Luxing Liu,Ziwei Gao,Chunyan Cui,Chuanchuan Fan,Yang Liu,Mingyuan Di,Qiang Yang,Ziyang Xu,Wenguang Liu

It has always been a huge challenge to construct high-strength hydrogels that are composed entirely of natural polymers. In this study, inspired by the structural characteristics of the extracellular matrix (ECM), gelatin and hydrazide alginate were employed to mimic the composition of collagen and glycosaminoglycans (GAGs) in the ECM, respectively, to develop natural polymer (NP) high-strength hydrogels crosslinked by physical and covalent interactions (Gelatin-HAlg-DN). First, HAlg and gelatin can form physically crosslinked hydrogels (Gelatin-HAlg) due to electrostatic and hydrogen bond interactions. Then, the Gelatin-HAlg hydrogels can be further covalently crosslinked in the presence of 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to obtain Gelatin-HAlg-DN hydrogels. The obtained Gelatin-HAlg-DN hydrogels exhibit considerably enhanced mechanical properties (tensile strength: 0.9 MPa; elongation at break: 177%) with a maximum 16- and 3.2-fold increase in tensile strength and elongation at break, respectively, compared with gelatin methacrylate (GelMA) hydrogels. Importantly, the Gelatin-HAlg-DN hydrogels exhibit excellent biodegradability and swelling stability under physiological conditions, and the capability to support cell adhesion and proliferation. In a rat critical size bone defect model, Gelatin-HAlg-DN hydrogels loaded with psoralen could effectively promote bone regeneration, showing appealing potential as tissue engineering scaffolds.

研究领域: 生物材料学 · 组织工程学 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF SURGICAL RESEARCH · 2012 · IF 2.247

The study of a new detergent (octyl-glucopyranoside) for decellularizing porcine pericardium as tissue engineering scaffold

Jiaoming Dong,Yu Li,Xiumei Mo

Background The use of extracellular matrix (ECM) derived from decellularized tissue is increasingly frequent in regenerative medicine and tissue engineering . However, it is recognized that currently used decellularization procedures have negative effects on ECM integrity. The objective of this study was to investigate the impact of a decellularization protocol with a new detergent on the ECM integrity of porcine pericardium (PP) compared with other traditional detergents. Materials and methods Fresh PP were decellularized by sodium deoxycholate in combination with Triton X-100 (SDT), sodium dodecyl sulfate (SDS), and octyl-glucopyranoside (OGP), respectively. Histologic analysis and scanning electron microscopy were performed to confirm the removal of cells and to examine the structure of ECM. DNA content was examined by the method of DNA extraction . Mechanical properties and biochemical compositions of ECM were also studied. Results Histologic analysis and DNA determination demonstrated that SDS and OGP completely removed the cells, and the major ECM structure was preserved well for PP treated with 1% (wt/vol) OGP but disrupted for PP treated with SDS; whereas treatment with SDT was insufficient to remove cells from PP. Uniaxial tensile tests showed that PP decellularized by OGP had similar mechanical properties to native PP, whereas the mechanical properties of PP decellularized by SDS and SDT decreased. The biochemical compositions of PP decellularized by OGP were also well conserved, except that glycosaminoglycans markedly decreased. Moreover, the results obtained in the MTT study further indicated that the cytotoxicity of PP decellularized by OGP was significantly lower than that decellularized by SDS and SDT. Conclusion It is suggested that the environmentally friendly and nontoxic OGP can be used as a decellularizing agent. The OGP method could achieve both complete removal of cells from native PP and preservation of the matrix structure; thus, it might be a suitable approach to preparation of tissue engineering heart valve scaffold.

CAS / MDL: 29836-26-8 60-00-4
研究领域: 再生医学 · 组织工程 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CARBOHYDRATE POLYMERS · 2019 · IF 6.044

Saccharides in straw hydrolysate decrease cell membrane damage by phenolics by inducing the formation of extracellular matrix in yeast

Xiahui Wang,Shouqing Cui,Jiajun Hu,Xiubing Ma,Tian-Ao Zhang,Yiu Fai Tsang,Jixiang Li,Min-Tian Gao

The bioconversion of rice straw into ethanol can alleviate the energy crisis and solve problems related to waste treatment. In this study, the effect of soluble polysaccharides (SPs) produced during rice straw saccharification on the formation of extracellular matrices (EMs) by the yeast Saccharomyces cerevisiae was investigated. SPs were characterized by high-performance liquid chromatography (HPLC) and fourier transform infrared spectroscopy (FT-IR). SPs reduced the inhibition of alcohol dehydrogenase activity by phenolic acids (PAs) and regulated the intracellular redox state, resulting in higher ethanol production. The results of flow cytometry, confocal laser scanning microscopy, and atomic force microscopy indicated that PAs changed microbial morphology and caused damage in microbial cell membranes. The protective effect of SPs against cell membrane damage could be attributed to the synthesis of polysaccharide-dependent extracellular matrix, which maintained cellular integrity even under phenolic acid stress. These findings provide new strategies to improve pretreatment and saccharification processes.

CAS / MDL: 9012-54-8
研究领域: 生物化学 · 微生物学 · 能源生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2022 · IF 5.999

Enhanced photothermal and chemotherapy of pancreatic tumors by degrading the extracellular matrix

Yuancun Cheng,Xiaoyi Zheng,Liying Zhang,Jiulong Zhao,Lianghao Hu,Shige Wang

The degradation of extracellular matrix (ECM) to increase drug permeability is an attractive approach to enhancing pancreatic cancer therapy efficiency. Herein, polypyrrole nanoparticles (PPy NPs) were prepared by a template-guided chemical oxidation method. These PPy NPs with abundant surface pores were used to load the anticancer drug doxorubicin (DOX). In order to intelligently control the DOX release, PPy/DOX NPs were further entrapped with a thermoresponsive ligand, lauric acid (LA), to form PPy-LA/DOX NPs. Bromelain (BL) was then grafted onto the surface of PPy-LA NPs or PPy-LA/DOX NPs through an amidation reaction with the carboxyl group of LA. It was found that the DOX release of PPy-LA/DOX NPs was pH and temperature responsive, reaching a maximum amount of 85.9% within 48 h at pH = 5.4 and 50 °C. Moreover, it was demonstrated that the resultant PLB (PPy-LA-BL) NPs could efficiently hydrolyze the collagen in ECM and enhance the permeability of DOX to the pancreatic tumor. Remarkably, PLB NPs not only featured admirable photothermal conversion but also exhibited obvious photoacoustic imaging capability, which enabled imaging-guided enhanced tumor ablation. This study is anticipated to provide a feasible strategy to improve the permeability of nanoparticles to tumors.

研究领域: 肿瘤学 · 生物医学工程 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2024 · IF 8.2

Recoverability of zebrafish from decabromodiphenyl ether exposure: The persisted interference with extracellular matrix production and collagen synthesis and the enhancement of arrhythmias

Yanli Xu,Qi Zhou,Jian Luan,Jing Hou

As a widely used brominated flame retardant, the widespread presence of decabromodiphenyl ether (BDE-209) in the natural environment and the toxicity risks it poses are well established, but the recoverability of BDE-209-induced individual injuries remains unknown. Therefore, a 7-day depuration experiment following a 4-day exposure of zebrafish to BDE-209 was conducted to confirm the recoverability and its mode of action. Oxidative stress after depuration was significantly reduced compared with BDE-209 exposure as indicated by the decreased expression level of oxidative stress-related genes and the reduced MDA, Gpx, and GST in zebrafish, indicating a gradual recovery of antioxidant activity. However, BDE-209 inhibition of extracellular matrix (ECM) proteins worsened after depuration. Mechanistically, BDE-209 mediated ECM production and secretion by down-regulating integrin expression. Furthermore, BDE-209 inhibition of collagen synthesis worsened after depuration. Biochemical assays and histopathological observations revealed a same result in zebrafish. Mechanistically, lysine hydroxylation is inhibited thereby affecting collagen synthesis. Interestingly, zebrafish showed arrhythmia after depuration compared to BDE-209 exposure, and abnormal changes in ATPase levels indicated that disturbances in Ca 2+ homeostasis contributed to arrhythmia. Collectively, BDE-209-induced interference with ECM production and collagen synthesis persisted after depuration, which will provide new insights for understanding the recovery patterns of individuals under BDE-209 stress.

CAS / MDL: 30525-89-4
研究领域: 环境毒理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2025 · IF 5.7

Macro/nano topological modification of silk fibroin mesh with mimicked extracellular matrix structure and excellent biocompatibility

Pei Cai,Ying Mao,Xinmei Liu,Zhiwei Li,Jinfeng Wang,Wenxing Chen,Hongshi Zhao,Wangyang Lu

Synthetic surgical meshes have been widely used for repairing hernias, but their performances, such as nonabsorbability and insufficient mechanical strength, require further improvement due to postsurgical complications, including chronic pain and inflammation. In this work, naturally derived and bioresorbable silk fibroin meshes (SFM) with three knit patterns were optimized and modified by a combination of regenerated silk fibroin (RSF) and polydopamine (PDA), to endow SFM with mimicked extracellular matrix (ECM) structure and excellent biocompatibility. Our study confirmed that the modified meshes (SFM@PDA-RSF) exhibited ECM-like structure and good structural stability. Tensile testing results revealed that SFM substrate played a dominant role in mechanical properties, and SFM@PDA-RSF showed high tensile strength (49.58 N/cm transversely, 68.42 N/cm longitudinally), which could afford sufficient mechanical support for abdominal wall hernia (AWH) repair (16 N/cm). Moreover, SFM@PDA-RSF was found to be significantly antioxidant, non-hemolytic, and favorable for cell adhesion and growth, showing great potential for effective hernia repair.

CAS / MDL: 7550-35-8
研究领域: 生物医学工程 · 材料科学 · 组织工程
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2025 · IF 9.7

Sulfur dioxide-releasing nanomotors improve the therapeutic effect of liver fibrosis by restoring the fenestrae of sinusoids

Lin Chen,Zhengwei Chen,Di Shi,Haifeng Ke,Chun Mao,Mimi Wan

The dual barriers formed by the capillarized liver sinusoids and excessive deposited extracellular matrix (ECM) significantly impede the retention of therapeutic agents in the fibrotic liver. Currently, there are limited reports on strategies capable of simultaneously overcoming these barriers. Here, we propose sulfur dioxide (SO 2 )-releasing nanomotors based on endogenous in vivo reactions to restore the fenestrae of sinusoids and degrade ECM by activating the endogenous signaling pathway to improve the retention of therapeutic agents in the damaged liver. These nanomotors leverage the specific enzyme concentration gradient in damaged liver tissue as a chemoattractant signal, guiding their targeted delivery. The nanomotors incorporate an l -cysteine-based substrate that, upon enzymatic catalysis, generates SO 2 . The released SO 2 can upregulate the cyclic guanosine monophosphate expression to restore the fenestrated phenotype of liver sinusoidal endothelial cells. Concurrently, SO 2 can stimulate the endogenous nitric oxide production to induce matrix metalloproteinase-1 activation to facilitate the collagen degradation. The animal experimental model also demonstrates the effective retention of nanomotors in damaged liver tissue and reversal of liver fibrosis.

CAS / MDL: 110-78-1 121-44-8
研究领域: 医学 · 药学 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioactive Materials · 2020 · IF 8.724

Hierarchical macro-microporous WPU-ECM scaffolds combined with Microfracture Promote in Situ Articular Cartilage Regeneration in Rabbits

Mingxue Chen,YangYang Li,Shuyun Liu,Zhaoxuan Feng,Hao Wang,Dejin Yang,Weimin Guo,Zhiguo Yuan,Shuang Gao,Yu Zhang,Kangkang Zha,Bo Huang,Fu Wei,Xinyu Sang,Qinyu Tian,Xuan Yang,Xiang sui,Yixin Zhou,Yufeng Zheng,Quanyi Guo

Tissue engineering provides a promising avenue for treating cartilage defects. However, great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and regeneration. In this study, decellularized cartilage extracellular matrix (ECM) and waterborne polyurethane (WPU) were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing (LDM) system, which combines rapid deposition manufacturing with phase separation techniques. The scaffolds successfully achieved hierarchical macro‐microporous structures. After adding ECM, WPU scaffolds were markedly optimized in terms of porosity, hydrophilia and bioactive components. Moreover, the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution, adhesion, and proliferation than the WPU scaffolds. Most importantly, the WPU-ECM scaffold could facilitate the production of glycosaminoglycan (GAG) and collagen and the upregulation of cartilage-specific genes. These results indicated that the WPU-ECM scaffold with hierarchical macro‐microporous structures could recreate a favorable microenvironment for cell adhesion, proliferation, differentiation, and ECM production. In vivo studies further revealed that the hierarchical macro‐microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit model. Six months after implantation, the repaired cartilage showed a similar histological structure and mechanical performance to that of normal cartilage. In conclusion, the hierarchical macro‐microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.

研究领域: 组织工程学 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2019 · IF 8.355

3D printing electrospinning fiber-reinforced decellularized extracellular matrix for cartilage regeneration

Weiming Chen,Yong Xu,Yaqiang Li,Litao Jia,Xiumei Mo,Gening Jiang,Guangdong Zhou

Cartilage decellularized matrix (CDM) is considered a promising biomaterial for fabricating cartilage tissue engineering scaffolds. An ideal CDM-based scaffold should possess customizable 3D shape for complex tissue regeneration and proper pore size for cell infiltration , as well as provide mechanical support for cell growth. 3D printing is an efficiently technique for preparing customizable 3D scaffolds, however, fabricating CDM-based 3D-printed scaffolds with customizable shapes, proper pore structure and satisfactory mechanical properties remains a challenge. In the current study, to achieve customizable CDM-based 3D scaffolds, CDM was successfully processed into inks suitable for 3D printing. Further, the poor mechanics of CDM-based scaffolds were significantly improved by adding electrospinning fiber into the CDM-based inks for 3D printing. Importantly, the 3D-printed electrospinning fiber-reinforced CDM-based scaffold presented good biocompatibility and can enhance repair articular cartilage defects in rabbits. The current study provides a novel strategy for printing electrospinning fiber-reinforced CDM-based scaffolds for tissue regeneration.

研究领域: 生物医学工程 · 组织工程 · 再生医学
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-18 · IF 15.7

Streamlined metal-based hydrogel facilitates stem cell differentiation, extracellular matrix homeostasis and cartilage repair in male rats

Li Wen,Shi Zhiyuan,Jing Huaqing,Dou Yunsheng,Liu Xinyi,Zhang Mengyao,Qiu Zitong,Heger Zbynek,Li Nan

Dysregulation of extracellular matrix (ECM) homeostasis plays a pivotal role in the accelerated degradation of cartilage, presenting a notable challenge for effective osteoarthritis (OA) treatment and cartilage regeneration. In this study, we introduced an injectable hydrogel based on streamlined-zinc oxide (ZnO), which is responsive to matrix metallopeptidase (MMP), for the delivery of miR-17-5p. This approach aimed to address cartilage damage by regulating ECM homeostasis. The ZnO/miR-17-5p composite functions by releasing zinc ions to attract native bone marrow mesenchymal stem cells, thereby fostering ECM synthesis through the proliferation of new chondrocytes. Concurrently, sustained delivery of miR-17-5p targets enzymes responsible for matrix degradation, thereby mitigating the catabolic process. Notably, the unique structure of the streamlined ZnO nanoparticles is distinct from their conventional spherical counterparts, which not only optimizes the rheological and mechanical properties of the hydrogels, but also enhances the efficiency of miR-17-5p transfection. Our male rat model demonstrated that the combination of streamlined ZnO, MMP-responsive hydrogels, and miRNA-based therapy effectively managed the equilibrium between catabolism and anabolism within the ECM, presenting a fresh perspective in the realm of OA treatment.

研究领域: 医学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Photodiagnosis and Photodynamic Therapy · 2022 · IF 3.577

Brain extracellular matrix attenuates photodynamic cytotoxicity of glioma cells

Cong Shen,Guoying Huang,Dan Hu,Hongjian Zhao

Glioma is the most common tumor in the central nervous system, which is often accompanied by poor prognosis. Brain extracellular matrix (ECM) plays an important role in regulating the growth and migration of glioma . Photodynamic therapy (PDT) has been an effective method for the treatment of solid tumors by oxidative modifications in recent years, and ECM may have an impact on the cytotoxicity of photodynamic therapy . In this work, we prepared decellularized brain ECM by chemical method to investigate the influence of the photodynamic effect of glioma C6 cells. Compared with decellularized liver ECM, brain ECM reduces PDT cytotoxicity. By observing the content of reactive oxygen species produced by near-infrared light active indocyanine green in cells, it was found that ECM did not affect the production of reactive oxygen species. Therefore, it is speculated that brain ECM may enhance the oxidative stress adaptability of glioma cells through potential signal regulation, or protect photodynamic targeting biomolecules (such as proteins and other cellular components) from oxidation in PDT mediated by indocyanine green and 808 nm laser in glioma cells.

研究领域: 肿瘤学 · 神经科学 · 生物医学工程
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