ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Xuan Pei,Haitao Peng,Ya Ren,Lina Wu,Donglin Ma,Changchun Zhou,Li Min,Yujiang Fan,Maling Gou
Osteoinductive biomaterials have emerged as promising platforms for bone regeneration. Nevertheless, conventional calcium phosphate-based systems exhibit suboptimal mechanical properties, particularly under load-bearing conditions, which severely restricts their clinical applicability in critical-sized defect repair. Here, a carbon-based scaffold fabricated through a 3D printing-pyrolysis strategy, featuring osteoinductive coralloid nanostructures on its surface is reported. The scaffold demonstrates a specific strength of 237.5 kN·m kg −1 , surpassing that of commercial orthopedic implants. Notably, the scaffold shows intrinsic osteoinductive properties through successful ectopic bone formation in gluteus maximus, a phenomenon attributed to its nanotopography-mediated activation of mechanotransduction pathways via Yes-associated protein (YAP) nuclear translocation. The scaffold outperformed titanium alloys in repairing both femoral bone defects and cranial bone defects in vivo. Its bone repair efficiency can be further improved by a biomimetic mineralization process. This work highlights the potential of a robust carbon scaffold with a nanostructured surface for osteoinductivity, which will lead to the development of future biomaterials for bone repair.
研究领域:
生物材料学
·
再生医学
·
骨科
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Hongyu Wang,Ruili Liu,Yue Yu,Hongrui Xue,Runjia Shen,Yanshuang Zhang,Jiandong Ding
Epithelial-mesenchymal transition (EMT) is a key phenotypic switch in cancer metastasis, leading to fatal consequences for patients. Under geometric constraints, the morphology of cancer cells changes in both cellular and subcellular levels, whose effects on EMT are, however, not fully understood. Herein, we designed and fabricated chimeric micropatterns of polystyrene (PS) with adhesion contrast to reveal the impacts of cell shapes and nuclear shapes on EMT in a decoupled way. Cell elongation was modulated via microwell aspect ratios (ARs), and nuclear deformation was generated through a micropillar array in the microwell. Human non-small cell lung cancer cells (A549) were cultured on the quasi-three dimensional micropatterned surfaces, and transforming growth factor-β1 (TGF-β1) was added to induce EMT. We found that chimeric micropatterns upregulated EMT with an increase of cellular AR and nuclear indentation under given TGF-β1. The subsequent assessment of the contractility and oriented assembly of microfilaments elucidated the key role of mechanotransduction in cell elongation and EMT, as proved by myosin inhibition, while it was obstructed by micropillars in the chimeric micropattern. Hence, the micropillar array possessed a nonmonotonic influence, enhancing the EMT of cells with AR of 1, but hindering the EMT with an impact more significant on microwells with large ARs due to the impeded cytoskeleton assembly. This fundamental research has illustrated the complex of cellular and subcellular geometries on cell behaviors including phenotype transition in cancer metastasis.
研究领域:
生物医学工程
·
细胞生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2024
·
IF 3.8
Jin Xue-Ke,Jin Kai-Qi,Yang Xiao-Ke,Wen Ming-Yong,Liu Yan-Ling,Huang Wei-Hua
Mechanotransduction is the essential process that cells convert mechanical force into biochemical responses, and electrochemical sensor stands out from existing techniques by providing quantitative and real-time information about the biochemical signals during cellular mechanotransduction. However, the intracellular biochemical response evoked by mechanical force has been poorly monitored. In this paper, we report a method to apply local stretch on single cell and simultaneously monitor the ensuing intracellular biochemical signals. Specifically, a ferromagnetic micropipette was fabricated to locally stretch a single cell labeled with Fe 3 O 4 nanoparticles under the external magnetic field, and the SiC@Pt nanowire electrode (SiC@Pt NWE) was inserted into the cell to monitor the intracellular hydrogen peroxide (H 2 O 2 ) production induced by the local stretch. As a proof of concept, this work quantitatively investigated the elevated amount of H 2 O 2 levels in single endothelial cell under different stretching amplitudes. This work puts forward a new research modality to manipulate and monitor the mechanotransduction at the single-cell level. Graphical abstract
研究领域:
生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
Yuyan Sun,Ziyu Luo,Haiqi Zhou,Sha Wu,Hongwei Shen,Yuanyuan Fu,Thai Namanh Ngo,Wen Wang,Yuanrong Wang,Ying Kong
Chondrocyte mechanotransduction dysfunction is a key feature of osteoarthritis (OA). Previous studies have demonstrated that primary cilia play a crucial role in chondrocyte mechanosensation and signal transduction. Transient Receptor Potential Vanilloid 4(TRPV4), which is highly expressed on primary cilia, is a critical mechanotransduction protein and one of the most important Ca 2+ channels. However, the interplay between the mechanism of primary cilia-mediated signaling and that of TRPV4 channel regulation remains poorly understood. Here, we demonstrate that OA chondrocytes and Intraflagellar Transport Protein 88(Ift88) conditional knockout (cKO) mice exhibit reduced ciliary incidence. This results in cartilage degeneration. TRPV4 expression inversely correlated with ciliary integrity, increasing as cilia were lost. In cilia-intact healthy chondrocytes, TRPV4 antagonism inhibited Ca 2+ -dependent NF-κB activation while promoting type II collagen(COL2) synthesis. These effects were abolished by Interleukin-1 beta(IL-1β)-induced ciliary defect or IFT88 deficiency. Chromatin immunoprecipitation(ChIP) analysis revealed disrupted p65 binding to the COL2 promoter upon the loss of ciliary integrity. Crucially, Ift88 cKO chondrocytes showed unresponsive of the TRPV4 channel, as confirmed by Ca 2+ flux and changes in the expression levels of NF-κB and COL2. Our findings position primary cilia as indispensable regulators of TRPV4-mediated NF-κB - COL2 signaling, offering mechanistic insights into OA pathogenesis and identifying IFT88 as a therapeutic checkpoint.
研究领域:
分子生物学
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细胞生物学
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骨关节炎病理学
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信号转导
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转化医学
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软骨生物学
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机械生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2025
·
IF 6.9
Zhuo Li,Zhengnan Guo,Zhengmeng Yang,Boguang Yang,Yuan Hu,Xian Xie,Zhixian Zong,Zekun Chen,Kunyu Zhang,Pengchao Zhao,Gang Li,Xuefeng Yang,Liming Bian
Intramembranous ossification, a major bone development process, begins with the condensation of precursor cells through the timely structural adaption of extracellular matrix (ECM) catering to rapid cellular morphological changes. Inspired by this, we design a highly cell-adaptable hydrogel to recapitulate an ECM-dependent mechanotransduction-metabolism-epitranscriptomics axis in mesenchymal stromal cells (MSCs). This hydrogel significantly enhances the E-cadherin-mediated cell-cell interactions of MSCs and promotes glucose uptake and tricarboxylic acid (TCA) cycle activities. We further show that elevated succinate inhibits fat mass and obesity-associated protein (FTO), a N6-methyladenosine (m 6 A) demethylase, thereby enhancing methyltransferase-like 3 (METTL3)-driven m 6 A methylation. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) indicates increased m 6 A methylation of runt-related transcription 2 (Runx2), a key osteogenic signaling factor, promoting osteogenesis of hydrogel-delivered MSCs and bone regeneration in critical-sized bone defects. Our findings reveal the mechanism underlying the critical impact of adaptable ECM structures on tissue development and provide valuable guidance for the design of ECM-mimetic cell carriers to enhance the therapeutic outcomes of regenerative medicine.
研究领域:
细胞生物学
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分子生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2025
·Vol. 22
·期 14
·3454-3463
·
IF 3.2
Chen Jiahao,Chen Mengting,Xie Zhiwen,Shen Luheng,Jiang Juntao,Xia Shujie
Background: Prostate cancer (PCa) poses a significant health burden for men, with docetaxel constituting the primary therapeutic option for patients with metastatic PCa. However, the mechanisms governing docetaxel resistance remain incompletely understood. Several studies have implicated the role of the extracellular matrix (ECM) stiffness in cancer drug resistance, yet the precise role of ECM stiffness in docetaxel resistance in PCa remains elusive. The aim of this study was to explore the influence of ECM stiffness on docetaxel resistance in PCa and elucidate the underlying molecular mechanisms, thereby providing novel insights into PCa treatment.Methods: Polyacrylamide gels of varying stiffness were utilized to mimic different ECM stiffness conditions. The sensitivity of PCa cells to docetaxel was evaluated using CCK-8, TUNEL staining, flow cytometry, and western blotting. RNA-seq was employed to analyze the transcriptomic effects of different ECM stiffness on PC-3 cells. Western blotting, qPCR, and siRNA were utilized to validate the regulatory role of the key gene in the sensitivity of PCa cells to docetaxel under varying stiffness conditions.Results: Our findings indicate that high ECM stiffness enhances docetaxel resistance in PCa cells by inhibiting docetaxel-induced apoptosis. This process is mediated through the integrin-related mechanotransduction pathway. Specifically, high ECM stiffness upregulates the expression of PRRX1, thereby promoting docetaxel resistance in PCa cells.Conclusions: High ECM stiffness promotes docetaxel resistance in PCa, with PRRX1 identified as a pivotal gene in this process. These findings contribute to a deeper understanding of the mechanisms underlying docetaxel resistance in PCa and may inform the development of novel therapeutic strategies.
研究领域:
肿瘤学
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药理学
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分子生物学
·
癌症研究
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Yu Xiaolei,Mukwaya Vincent,Wang Li,Zhao Weili,Mann Stephen,Dou Hongjing
The mechanisms underlying the probing and response of cells to direct cell-presented mechanical signals generated in the local microenvironment are important controllers of diverse cell behaviours. Here we construct a model artificial pathogen cell with the similar compartmentalization architecture and same range of tunable rigidity as found in natural cells. By incubating the artificial cells with macrophages, we investigate the mechanisms of mechano-crosstalk between living cells and model protocells. We show that macrophages are equipped with distinct pseudopodia that facilitate the probing of cell-presented mechanical signals. Increasing the rigidity of the artificial pathogen cells enhances the proinflammatory polarization of the macrophages by promoting the docking of the mechanosensitive molecular clutch, actin assembly, and pseudopodia extension. The relationship between cell morphology and functional plasticity involves a mechano-transduction axis including artificial cell rigidity, pseudopodia, and macrophage inflammatory response. Taken together, our model protocells provide a new platform to decouple cell-presented mechanical signals and highlight their role in governing protocell-living cell mechano-crosstalk.
研究领域:
生物医学工程
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细胞生物学
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免疫学
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生物材料
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2025
·Vol. 10
·期 1
·1-19
·
IF 52.7
Wang Baile,Liu Jie,Wang Qin,Arhatte Malika,Cheong Lai Yee,Glogowska Edyta,Jiang Xue,Chung Sookja Kim,Jin Leigang,Hu Qianxing,Wang Yu,Honoré Eric,Xu Aimin
With aging or osteoporosis, bone marrow adipogenesis is increased and inversely correlates with the loss of bone mass. Bone marrow adipocytes are derived from multipotent bone marrow mesenchymal stem cells (BMMSCs), which can differentiate into either fat or bone. BMMSCs are mechanosensitive cells, but how mechanical loading is implicated in the in vivo regulation of bone marrow adipogenesis and its impact on bone remodeling remain poorly understood. Here, we identify the mechanosensitive cationic channel Piezo1 in BMMSCs as a key suppressor of bone marrow adipogenesis by preventing local inflammation, thereby enhancing osteoblast differentiation and bone formation. Mice with a specific Piezo1 invalidation in BMMSCs exhibit osteoporosis and marrow adiposity, together with resistance to the beneficial effects of exercise on bone health. Accordingly, Piezo1-deficient BMMSCs in vitro preferentially differentiate into adipocytes rather than osteoblasts. Invalidation of Piezo1 in BMMSCs enhances the autocrine activation of CCR2 by Ccl2, which further induces lipocalin-2 (Lcn2) production via NF-κB activation, thereby promoting adipocyte differentiation. Conversely, Piezo1 opening induces Klf2 expression through CaMKII, preventing c-Jun activation, Ccl2 production and bone marrow adipogenesis. These findings demonstrate that Piezo1 activation in BMMSCs suppresses bone marrow adipogenesis to maintain bone strength by preventing the Ccl2-Lcn2 inflammatory autocrine loop, thus uncovering a previously unrecognized link between mechanotransduction, inflammation, and cell fate determination.
研究领域:
骨生物学
·
干细胞生物学
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机械转导
·
炎症与免疫
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代谢性骨病
·
分子细胞生物学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2023
·
IF 12.4
Chen Li,Zihui Zheng,Xiang Wu,Qiu Xie,Ping Liu,Yunfeng Hu,Mei Chen,Liming Liu,Wangxing Zhao,Linlin Chen,Jun Guo,Ying Song
Rationale: Cells migrating through interstitial matrix enables stiffening of the tumor micro-environment. To overcome the stiff resistance of extracellular matrix, aggressive cells require the extracellular mechanosensory activation and intracellular tension response. Mechanotransduction linker srGAP2 can synergistically control the mechanical-biochemical process of malignant cell migration. Methods: To mimic the tumor micro-environment containing abundant collagen fibers and moving durotaxis of triple-negative breast cancer cells, the stiff-directed matrix was established. The newly designed srGAP2 tension probe was used to real-time supervise srGAP2 tension in living cells. The phosphorylation sites responsible for srGAP2 tension were identified by phosphorylated mutagenesis. Transwell assays and Xenograft mouse model were performed to evaluate TNBC cells invasiveness in vitro and in vivo . Fluorescence staining and membrane protein isolation were used to detect protein localization. Results: The present study shows srGAP2 serves as a linker to transmit the mechanical signals among cytoskeleton and membrane. SrGAP2 exhibits tension gradients among different parts in the stiff-directionally migrating triple-negative breast cancer cells. Cells showing the polarized tension that increased in the leading edge move faster, particularly guided by the stiff interstitial matrix. The srGAP2 tension-directed cell migration results from the upstream events of PKCα-mediated phosphorylation at Ser 206 in the F-bar domain of srGAP2. In addition, Syndecan-4 (SDC4), a transmembrane mechanoreceptor protein, drives PKCα regional recruit on the area of membrane trending deformation, which requires the distinct extent of extracellular mechanics. Conclusion: SDC4-PKCα polarized distribution leads to the intracellular tension gradient of srGAP2, presenting the extra- and intracellular physiochemical integration and essential for persistent cell migration in stiff matrix and caner progression. Targeting the srGAP2-related physicochemical signaling could be developed into the therapeutic strategies of inhibiting breast cancer cell invasion and durotaxis.
研究领域:
癌症生物学
·
细胞生物学
·
机械生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Ximin Yuan,Zhou Zhu,Pengcheng Xia,Zhenjia Wang,Xiao Zhao,Xiao Jiang,Tianming Wang,Qing Gao,Jie Xu,Debin Shan,Bin Guo,Qingqiang Yao,Yong He
Tough hydrogel has attracted considerable interest in various fields, however, due to poor biocompatibility, nondegradation, and pronounced compositional differences from natural tissues, it is difficult to be used for tissue regeneration. Here, a gelatin-based tough hydrogel (GBTH) is proposed to fill this gap. Inspired by human exercise to improve muscle strength, the synergistic effect is utilized to generate highly functional crystalline domains for resisting crack propagation. The GBTH exhibits excellent tensile strength of 6.67 MPa (145-fold that after untreated gelation). Furthermore, it is directly sutured to a ruptured tendon of adult rabbits due to its pronounced toughness and biocompatibility, self-degradability in vivo, and similarity to natural tissue components. Ruptured tendons can compensate for mechanotransduction by GBTH and stimulate tendon differentiation to quickly return to the initial state, that is, within eight weeks. This strategy provides a new avenue for preparation of highly biocompatible tough hydrogel for tissue regeneration.
研究领域:
生物材料
·
组织工程
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Yiwen Zhou,Lili Chen,Miaomiao Han,Peixiang Zhu,Yanyi Wang,Xuanxuan Yu,Tingyu Reng,Huijuan Wang,Baochao Li,Caixia Zhang,Ziwei Huang,Shuang Lin,Guoyun Wang,Jie Ge,Baosheng Guo,Huang Li
Maxillary underdevelopment is a critical component of skeletal Class III malocclusion, closely linked to altered biomechanical signaling. Mechanical stimulation through early facemask protraction can effectively promote maxillary growth, yet the underlying mechanotransduction mechanisms remain unclear. In this study, fibroblast growth factor 9 (FGF9) is identified as a key biomechanical responder in maxillary development. Secreted predominantly by osteocytes, FGF9 interacts with fibroblast growth factor receptor 2 (FGFR2) on preosteoblasts to inhibit osteogenic differentiation. Mechanical stress reduces FGF9 secretion from osteocytes, thereby relieving its inhibitory effect and enhancing osteogenesis. Mechanistically, FGF9 promotes nuclear translocation of FGFR2 in preosteoblasts, which modulates transcription factors ATF5 and NR2F1 to suppress bone formation. In vivo, targeted overexpression of FGF9 in bone tissue led to significant maxillary growth impairment, underlying the pathological impact of disrupted mechanical signaling. These findings reveal a novel osteocyte–preosteoblast axis regulated by FGF9–FGFR2 signaling in response to mechanical stimulation and provide mechanistic insight into how biomechanical forces shape craniofacial development. This pathway offers new mechanistic insights and potential therapeutic targets for correcting craniofacial skeletal abnormalities.
研究领域:
发育生物学
·
分子生物学
·
生物力学
·
颅面遗传学
·
骨生物学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2021
·Vol. 8
·期 13
·2003738
·
IF 16.806
Yu Qin,Xue-Bo Hu,Wen-Ting Fan,Jing Yan,Shi-Bo Cheng,Yan-Ling Liu,Wei-Hua Huang
In the field of three-dimensional (3D) cell culture and tissue engineering, great advance focusing on functionalized materials and desirable culture systems has been made to mimic the natural environment of cells in vivo. Mechanical loading is one of the critical factors that affect cell/tissue behaviors and metabolic activities, but the reported models or detection methods offer little direct and real-time information about mechanically induced cell responses. Herein, for the first time, a stretchable and multifunctional platform integrating 3D cell culture, mechanical loading, and electrochemical sensing is developed by immobilization of biomimetic peptide linked gold nanotubes on porous and elastic polydimethylsiloxane. The 3D scaffold demonstrates very good compatibility, excellent stretchability, and stable electrochemical sensing performance. This allows mimicking the articular cartilage and investigating its mechanotransduction by 3D culture, mechanical stretching of chondrocytes, and synchronously real-time monitoring of stretch-induced signaling molecules. The results disclose a previously unclear mechanotransduction pathway in chondrocytes that mechanical loading can rapidly activate nitric oxide signaling within seconds. This indicates the promising potential of the stretchable 3D sensing in exploring the mechanotransduction in 3D cellular systems and engineered tissues.
研究领域:
组织工程
·
生物材料
·
细胞生物学
·
生物医学工程
✓ 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）