CHEMICAL ENGINEERING JOURNAL
·
2025
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IF 13.2
Xiaoqian Ding,Jieliang Shen,Jindong Tan,Fan Wang,Weiwei Yi,Zijie Wang,Xinhe Li,Xinyu Zhang,Yi He,Wang Han,Mengtong Guan,Bo Liao,Juan Wang,Xiaoyu Han,Dingqun Bai
The disruption of endogenous electric field (EF) and subsequent degradation of the extracellular matrix (ECM) and joint wear are the fundamental pathological mechanisms underlying Osteoarthritis (OA). The key to reversing OA and promoting cartilage repair lies in restoring the endogenous electric field, improving lubrication performance between articular cartilage, and achieving a catabolic balance of ECM. In this study, we utilized short fiber fabrication technology and one-step surface dopamine grafting technology to construct a “PLA/ G@β-Gly /GO/PMPC” lubricated electroactive short fiber. By utilizing an “ultrasonic piezoelectric transducer” to generate electrical signals, we promoted ECM synthesis, restored endogenous EF, repaired hydration lubrication layer, and stabilized the endogenous electric field. This approach enables regeneration and optimization of articular cartilage while breaking free from the detrimental cycle associated with OA. Under ultrasonic stimulation at 1 W, 650 KHz frequency, and 50 % duty cycle, the lubricated electroactive short fiber generated a significant electrical signal of 1.31 V which upregulated Sirt1 expression in OA chondrocytes. It improved mitochondrial function and increased ATP capacity to 23.074 ± 1.87 pmol/min. Furthermore, incorporating different proportions of lubricating molecules (1:1, 1:4, and 1:8) into the material reduced the coefficient of friction (COF) between articular cartilages from approximately 0.725–0.693 to about 0.235. This improvement enhanced lubrication performance between articular cartilages by inhibiting ECM degradation and stabilizing endogenous EF. The innovative composite electrospun material exhibits great potential in promoting OA cartilage repair.
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
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产品关联
DOI
高影响因子
Biofabrication
·
2026
·Vol. 18
·期 2
·025041
·
IF 8.2
Shaoshuai Song,Wenxing Li,Ya Fang,Zhen Fang,Hong Zeng,Dandan Li,Youzhuan Xie,Junjie Niu,Jinwu Wang
Bone microtissue grafts mimicking skeletal features and organogenesis are an emerging strategy, different from the traditional tissue engineered bone grafts using the three-dimensional (3D) cell encapsulation and the top cell seeding, and remain challenging in regenerative medicine and drug discovery, because the existing scaffold-free and microcarrier-based microtissue systems are difficult to manipulate the microtissue morphologies towards native bone microstructures limited by their mechanical weakness and the absence of interconnected inner cavities. Herein, we synthesized a supramolecular cryogel by an ice-templated freezing-polymerization process, acquiring a promising microcarrier resembling native bone trabecular morphology for 3D culture of trabecular bone microtissue grafts. In our strategy, a macromolecular chitosan monomer and two supramolecular monomers including glycinamide and phytic acid constituted the supramolecular cryogel, the modification using glycinamide and phytic acid components enables the cryogel microcarrier with porous cavities and compression-resistant abilities like the native trabecular bone tissues. Moreover, the mineralization of the cryogel microcarriers was also improved by the modification of phytic acid monomers, consequently strengthening osteogenic differentiation of bone-marrow-derived mesenchymal stem cells and in vitro microtissue biomineralization. The in vivo results also revealed that a trabeculae-like bone microtissue forms on the cryogel microcarriers, with vessel invasion into inner cavities of the trabecular bone microtissues. After in situ implantation of the prepared trabecular bone microtissues, the bone regeneration characterized by raising bone mineral density and remodeling bone trabecular microstructures was observed on a rat femur condyle defect model. Last but not least, we also discovered the intestinal bacterial communities and compositions are closely related to the bone regeneration after implantation of the engineered bone microtissue grafts, which is the first evidence focusing on the intestinal microbiota response to the bone injury and bone regeneration events representing a feasible approach to bone regeneration examination. In brief, the supramolecular cryogels we developed in this study have been proved to be a promising microcarrier for the construction and 3D culture of trabecular bone microtissues, and this work offers a novelty insight into microtissue engineering and bone regeneration.
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Communications
·
2022
·
IF 3.662
Xinyu Xu,Hao Wang,Shuling Zhang,Xiaohan Mei,Boda Ying,Ruiyan Li,Yanguo Qin
High-performance polymers, such as polyetherimide (PEI), are promising bone biomaterials that meet the mechanical demands of bone defect repair. To achieve better therapeutic outcomes, the osteoinduction of high-performance polymers requires further improvement. In this study, the fused deposition modeling (FDM) 3D printing method was applied to fabricate orthogonal porous PEI scaffolds. Inspired by the simulation of the extracellular matrix (ECM), The polydopamine (PDA) and Arg-Gly-Asp (RGD) peptides were applied to construct an osteogenic microenvironment on PEI/PDA/RGD scaffold. The characterization, bioactivity, and osteogenic differentiation of the scaffolds were systematically investigated. The mechanical properties of the PEI/PDA/RGD scaffold were similar to those of bone tissues with favorable hydrophilicity and no biotoxicity. The adhesion, proliferation, extracellular bone matrix formation, calcium deposition, and alkaline phosphatase (ALP) vitality of MC3T3-E1 osteoblasts was higher in the PEI/PDA/RGD scaffold compared with other scaffolds. The PEI/PDA/RGD scaffold promoted the osteogenic differentiation of MC3T3-E1 osteoblasts by upregulating their gene expression of osteopontin (OPN), runt-related transcription factor 2 (RUNX-2), bone morphogenetic protein (BMP-2), osteocalcin (OCN), ALP, and especially type I collagen (COL-1). The PEI/PDA/RGD scaffold fabricated in this study is a promising bone biomaterial with appropriate mechanical properties and ideal osteogenic microenvironment, which has potential application in the field of bone defect repair. The construction of osteogenic microenvironment on 3D printed porous PEI scaffold could broaden the application of polyetherimide in bone biomaterials.
研究领域:
生物材料
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组织工程
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生物医学工程
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细胞生物学
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产品关联
DOI
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2022
·
IF 4.145
Runze Zhao,Li Yang,Shuangjian He,Tingting Xia
Intervertebral disc degeneration (IVDD) is a main contributor to induce low back pain, and the pathogenic mechanism of IVDD remains unclear. The nucleus pulposus (NP) is a component of the intervertebral disc (IVD) that provides protection from mechanical stimuli. The matrix stiffness of NP tissue increases during the process of disc degeneration. Although several studies have found that pathological mechanical stimuli induce NP cell senescence, which is relevant for NP degeneration, however, the effect of matrix stiffness on NP cell senescence is not clear. Therefore, in the present study, we used polyvinyl alcohol (PVA) hydrogel with controllable stiffness to mimic the matrix stiffness of normal (4 kPa) and severely degenerated (20 kPa) NP tissue. Rat NP cells were isolated and cultured on substrates with different stiffness, and the cell proliferation , SA-β-gal activity, cell cycle, telomerase activity and the phenotype markers of NP cells were analyzed. Moreover, cytoskeleton staining and NP cellular Young's modulus on different substrates were also measured. To further investigate how substrate stiffness affects NP cell senescence, lysyl oxidase (LOX) was used to restore the extracellular matrix (ECM) synthesis of NP cells. The expression levels of integrin β1 and p38 MAPK were then measured. Our results showed that the 20 kPa substrate significantly induced NP cell senescence compared to the 4 kPa substrate. NP cells cultured on the 20 kPa substrate failed to maintain the expression of their phenotype markers. Furthermore, the 20 kPa substrate induced an increase of Young's modulus of NP cells, which possibly through up regulating the expressions of integrin β1 and p38 MAPK. These results indicated that the integrin β1-p38 MAPK signaling pathway may participated in substrate stiffness induced senescence of NP cells. LOX significantly increased ECM synthesis and inhibited substrate stiffness induced NP cell senescence, which indicated that matrix mechanics may be essential for maintaining the function of NP cell. Our results may provide a new perspective on the mechanism of IVDD by pathological matrix mechanics.
研究领域:
骨科
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细胞生物学
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生物力学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Liyue Zhou,Qiangwei Liang,Yifan Li,Yongjing Cao,Juan Li,Jiayu Yang,Jinxia Liu,Jiawei Bi,Yanhua Liu
Liver fibrosis is a pathological process of multiple chronic liver diseases progressing to cirrhosis for which there are currently no effective treatment options. During fibrosis progression, the overproduction of extracellular matrix (ECM) collagen secreted by hepatic stellate cells (HSCs) greatly impedes drug delivery and reduces drug therapeutic effects. In this study, a glycyrrhetinic acid (GA)-conjugated prodrug micellar system with collagenase I (COL) decoration (COL-HA-GA, abbreviated as CHG) was designed to codelivery sorafenib (Sora/CHG, abbreviated as S/CHG) for potentiating ECM degradation and HSCs targeting on liver fibrosis therapy. In ECM barrier models established in vitro or in vivo , CHG micelles efficiently degraded pericellular collagen and demonstrated enormous ECM penetration abilities as well as superior HSCs internalization . Moreover, CHG micelles exhibited more Sora & GA accumulations and activated HSCs targeting efficiencies in the fibrotic livers than those in the normal livers. More importantly, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating the fibrosis-related factors, leading to reverse the fibrotic liver to normal liver through the multi-mechanisms including angiogenesis reduction, liver fibrosis microenvironment regulation, and epithelial-mesenchymal transition inhibition. In conclusion, the developed COL decorated nano-codelivery system with fibrotic ECM collagen degradation and activated HSCs targeting dual-functions exhibited great potential for liver fibrosis therapy. Statement of significance A glycyrrhetinic acid (GA)-conjugated prodrug with collagenase I (COL) decoration (CHG) was designed for codelivery with sorafenib (S/CHG), potentiating extracellular matrix (ECM) degradation-penetration and hepatic stellate cells (HSCs) targeting on liver fibrosis therapy. In ECM barrier models, CHG micelles efficiently degraded pericellular collagen and demonstrated ECM penetration abilities, as well as displayed superior HSCs internalization. Moreover, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating cytokines, reversing the fibrotic liver to normal through various mechanisms. In conclusion, the developed fibrotic ECM degradation and HSCs targeting dual-functional nano-codelivery system provided a prospective potentiality in liver fibrosis therapy.
研究领域:
药理学
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纳米技术
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肝病学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2023
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IF 5.2
Qiaoli Wu,Bing Liu,Rongxian Yu,Xiaoling Sun,Ziyan Wang,Jun Zhou,Chenyang Lu,Jing Zhang,Jiaojiao Han,Xiurong Su
Osteoarthritis (OA) is a chronic disease associated with bone and muscle degeneration that causes great disturbances to daily lives. Skipjack tuna elastin peptides (STEP) is a kind of small molecule mixed peptides extracted from skipjack tuna bulbus cordis that have multiple active functions, including anti-inflammatory activity. However, it is ambiguous whether STEP reduce OA inflammation. Zebrafish served as a model in the present research for verifying the anti-inflammatory efficacy of STEP. Then, the composition of STEP was figured out by LC-MS/MS analysis, and the potential anti-inflammatory peptides were screened by molecular docking and microscale thermophoresis (MST). Finally, in vitro experiments were conducted on the potential peptides. According to the in vivo findings, STEP protected the cartilage tissues of zebrafish and regulated the expression of inflammatory factors and the JAK2/STAT3 signaling pathway . The in vitro results showed that the potential peptides (LGVGSPPGK, GFDPSR and PGAPGGGFDI) positively regulated the inflammatory responses and the JAK2/STAT3 signaling pathway and were effective in inhibiting extracellular matrix (ECM) degeneration and chondrocyte apoptosis. As a consequence, STEP possess anti-inflammatory and chondroprotective effects and could be a functional product for the alleviation of OA.
研究领域:
药理学
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生物技术
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生物化学
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炎症研究
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骨科
✓ 已验证
产品关联
DOI
高影响因子
Biomimetics
·
2026
·Vol. 11
·期 8
·599
·
IF 4.2
Haiguang Zhang,Feng Jiang,Qianmin Gao,Qingxi Hu,Jiaxuan Feng
Vascular stent implantation is a major treatment for vascular diseases, yet postoperative infection and persistent inflammation increase the risk of in-stent restenosis. Herein, core–shell structured PCL/PEO-PVP fiber membranes co-loaded with ciprofloxacin hydrochloride (CIP) and curcumin (CUR) were fabricated via coaxial electrospinning. Orthogonal experiments were conducted to optimize critical spinning parameters through multi-index comprehensive evaluation. Characterizations confirm intact core–shell architecture and stable polymeric backbone structure. In vitro release tests reveal sequential drug-delivery behavior: a rapid initial release of hydrophilic CIP and a delayed sustained release of hydrophobic CUR were observed, contributing to early-stage antibacterial and long-term anti-inflammatory effects, respectively. The “antibacterial zone” method verifies favorable antibacterial activity againstStaphylococcus aureus(S. aureus) andEscherichia coli(E. coli). ELISA results demonstrate the enhanced anti-inflammatory capacity of the dual-drug-loaded coaxial fiber membrane. Cellular assays confirm satisfactory cytocompatibility, and endothelial cells achieve normal proliferation and exhibit typical polygonal morphology on the membrane surface. This dual-drug-loaded coaxial-fiber membrane realizes coordinated sequential antibacterial and anti-inflammatory properties, which provides a feasible strategy for developing functional coatings toward vascular stents.
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产品关联
DOI
高影响因子
Small
·
2026
·
IF 11.8
Xin Li,Huanhuan Zhao,Xinqiang Hu,Hao Wei,Menghuan Li,Yanhua Hou,Kaiyong Cai,Yan Hu
Titanium (Ti) implants are widely used for treating bone fractures, but their clinical success is often limited by high failure rates due to the excessive osteoclastogenic activation of osteoclast precursor cells (OPCs) at the implantation site, particularly in patients with osteoporosis. Notably, the excessive osteoclastic differentiation of OPCs potently disrupts the osteogenesis-angiogenesis coupling to promote osteoclast-mediated osteolysis while dismantling the pro-osteogenic type H vascular niches, resulting in elevated risk of implant destabilization. To address this issue, here we report a biomineralization-tuned extracellular matrix (ECM)-mimetic biomineralized coating (TCC@Har-CaG) to enable redox rewiring of OPCs for promoting new bone formation. Specifically, we employed collagen-I as the substrate material to fabricate the stimuli-responsive biomineralized coating for the cooperative delivery of antioxidative gallic acid (GA) and osteoclast precursor cell inhibitor Harmine. The TCC@Har-CaG coating could sustainably release GA after implantation to effectively relieve reactive oxygen species (ROS) stress at the osteoporotic bone defects, which could synergize with Harmine to efficiently induce OPC quiescence and restore osteogenesis-angiogenesis coupling, thus cooperatively promoting new bone generation. This study presents a potential tactic for addressing osteoporotic bone fractures in clinical settings.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Yao Chen,Zhanghao Huang,Cheng Ji,Jia-Hai Shi
Background Biomaterials can improve cardiac repair combined with transplantation of bone marrow mononuclear cells (BMMNCs). In this study, we compared the phenotype and cardiac repair between human heart valve-derived scaffold (hHVS) and natural protein/polycaprolactone (NP/PCL) anchored BMNNCs. Methods and results BMMNCs were obtained from mice five days following myocardial infarction. Subsequently, BMMNCs were separately cultured on hHVS and PCL. Proliferation and cardiomyogenic differentiation were detected in vitro. Cardiac function was measured after transplantation of cell-seeded cardiac patch on MI mice. After that, the BMMNCs were collected for mRNA sequencing after culturing on the scaffolds. Upon anchoring onto hHVS or PCL, BMMNCs exhibited an increased capacity for proliferation in vitro, however, the cells on hHVS exhibited superior cardiomyogenic differentiation ability. Moreover, both BMMNCs-seeded biomaterials effectively improved cardiac function after 4 weeks of transplantation, with reduced infarction area and restricted LV remodeling. Cell-seeded hHVS was superior to cell-seeded PCL. Conclusion BMMNCs on hHVS showed better capacity in both cell cardiac repairing and improvement for cardiac function than on PCL. Compared with seeded onto PCL, BMMNCs on hHVS had 253 genes up regulated and 189 genes down regulated. The reason for hHVS’ better performance than PCL as a scaffold for BMMNCs might be due to the fact that optimized method of decellularization let more cytokines in ECM retained.
研究领域:
心血管医学
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再生医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Li Yang,Haoshuang Wu,Lu Lu,Qing He,Boting Xi,Hongchi Yu,Rifang Luo,Yunbing Wang,Xingdong Zhang
Collagen, a central component of the extracellular matrix (ECM), has been widely applied in tissue engineering , among others, for wound healing or bone and nerve regeneration . However, the inherent thrombogenic properties of collagen hinder the application in blood-contacting devices. Herein, a brand-new recombinant human type III collagen (hCOLIII) was explored that does not present binding sites for platelets while retaining the affinity for endothelial cells. The hCOLIII together with hyaluronic acid (HA) were deposited on the substrates via layer-by-layer assembly to form an ECM-mimetic multilayer coating . In vitro platelet adhesion and ex vivo blood circulation tests demonstrated prominent thromboprotective properties for the hCOLIII-based ECM-mimetic coating. In addition, the coating effectively guided the vascular cell fate by supporting the proliferation of endothelial cells and inhibiting the proliferation of smooth muscle cells by differentiating them to a more contractile phenotype. A polylactic acid (PLA) stent coated with hCOLIII-based ECM-mimetic coating was implanted in the abdominal aorta of rabbits to investigate the healing of the neointima. The enhanced endothelialization , suppressed inflammatory response, inhibition of excessive neointimal hyperplasia, and the superior thromboprotection strongly indicated the prospect of the hCOLIII-based ECM-mimetic coating as a tailored blood-contacting material for cardiovascular stents .
研究领域:
生物材料
·
组织工程
·
心血管医学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL
·
2024
·
IF 45.5
Jinjia Zhang,Junhong Li,Yongqiang Hou,Yao Lin,Hao Zhao,Yiran Shi,Kaiyun Chen,Cheng Nian,Jiayu Tang,Lei Pan,Yunzhi Xing,Huan Gao,Bingying Yang,Zengfang Song,Yao Cheng,Yue Liu,Min Sun,Yueyue Linghu,Jiaxin Li,Haitao Huang,Zhangjian Lai,Zhien Zhou,Zifeng Li,Xiufeng Sun,Qinghua Chen,Dongxue Su,Wengang Li,Zhihai Peng,Pingguo Liu,Wei Chen,Hongling Huang,Yixin Chen,Bailong Xiao,Lilin Ye,Lanfen Chen,Dawang Zhou
Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8 + T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8 + T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8 + T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8 + T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8 + T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8 + T cell exhaustion and could be targeted to potentiate cancer immunotherapy.
研究领域:
免疫学
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癌症生物学
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细胞生物学
·
转录调控
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2023
·
IF 10.7
Wenjuan Tang,Yu Hu,Kaihui Tu,Zhengyan Gong,Man Zhu,Tianfeng Yang,Ammar Sarwar,Bingling Dai,Dongdong Zhang,Yingzhuan Zhan,Yanmin Zhang
Introduction Tumor-associated calcium signal transducer 2 (Trop2) has been used as a transport gate for cytotoxic agents into cells in antibody–drug conjugate designs because of its expression in a wide range of solid tumors. However, the specific role of Trop2 itself in breast cancer progression remains unclear and small molecules targeting Trop2 have not yet been reported. Objectives To screen small molecules targeting Trop2, and to reveal its pharmacological effects and the molecular mechanisms of action. Methods Small molecule targeting Trop2 was identified by cell membrane chromatography, and validated by cellular thermal shift assay and point mutation analyses. We investigated the pharmacological effects of Trop2 inhibitor using RNA-seq, human foreskin fibroblast (HFF)-derived extracellular matrix (ECM), Matrigel drop invasion assays, colony-forming assay, xenograft tumor model, 4T1 orthotopic metastasis model and 4T1 experimental metastasis model. The molecular mechanism was determined using immunoprecipitation, mass spectrometry, immunofluorescence, immunohistochemistry and Western blotting. Results Here we identified Bruceine D (BD) as the inhibitor of Trop2, and demonstrated anti-metastasis effects of BD in breast cancer. Notably, Lys307 and Glu310 residues of Trop2 acted as critical sites for BD binding. Mechanistically, BD suppressed Trop2-induced cancer metastasis by blocking the formation of Trop2/β-catenin positive loop, in which the Trop2/β-catenin complex prevented β-catenin from being degraded via the ubiquitin-proteosome pathway. Destabilized β-catenin caused by BD reduced nucleus translocation, leading to the reduction of transcription of Trop2, the reversal of epithelial-mesenchymal transition (EMT) process, and the inhibition of ECM remodeling, further inhibiting cancer metastasis. Additionally, the inhibitory effects of BD on lung metastatic colonization and the beneficial effects of BD on prolongation of survival were validated in 4T1 experimental metastasis model. Conclusions These results support the tumor-promoting role of Trop2 in breast cancer by stabilizing β-catenin in Trop2/β-catenin positive loop, and suggest Bruceine D as a promising candidate for Trop2 inhibition.
研究领域:
肿瘤学
·
药理学
·
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）