Bio-Design and Manufacturing
·
2025
·Vol. 8
·期 3
·423-441
·
IF 7.6
Mi Xuelian,Ren Ya,Wang Hanbo,Qiang Lei,Kong Weiqing,Wang Hui,Yang Xue,Liu Yihao,Yang Han,Xiao Di,Ma Zhenjiang,Xu Guoxing,Zhang Changru,Wang Jinwu
In the current settings of osteosarcoma research and drug screening, in vitro three-dimensional (3D) models, which overcome the limitations of traditional models, are favored. In in vitro 3D models, tumor microenvironment simulation, particularly of the mechanical microenvironment, is crucial for estimating the biological effects of a tumor. However, current in vitro osteosarcoma model construction is often limited to a single mechanical signal, which fails to simulate the diversity of osteosarcoma mechanical stimuli. In this study, we utilized embedded bioprinting technology and the multiple response properties of calcium ions in soft and hard stiffness systems with osteosarcoma cell biological functions to construct an integrated gradient biomechanical signal-tailored osteosarcoma model (IGBSTOM). We achieved this by printing a fibrinogen bioink containing calcium ions and osteosarcoma tumor spheroids within an extracellular matrix composed of methacryloylated alginate, methacryloylated gelatin, thrombin, and transglutaminase, which is rich in polysaccharides and proteins and exhibits self-healing properties. Our in vitro and in vivo studies showed that the IGBSTOM enhanced tumor stemness, proliferation, and migration, and successfully reproduced the nest-like structure of tumors, providing an in vitro research platform that is more similar to the natural tumor than the existing models. This study proposes a novel IGBSTOM construction and provides a new strategy for the clinical understanding of tumor development, drug screening, and exploration of drug resistance and metastasis mechanisms.
研究领域:
肿瘤学
·
生物医学工程
·
细胞生物学
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产品关联
DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2023
·
IF 3.1
Yan Wang,Xiaoning Han,Linhong Deng,Xiang Wang
Tunneling nanotubes (TNTs) are elastic tubular structures that physically link cells, facilitating the intercellular transfer of organelles, chemical signals, and electrical signals. Despite TNTs serving as a multifunctional pathway for cell-cell communication, the transmission of mechanical signals through TNTs and the response of TNT-connected cells to these forces remain unexplored. In this study, external mechanical forces were applied to induce TNT bending between rat kidney (NRK) cells using micromanipulation . These forces, transmitted via TNTs, induced reduced curvature of the actin cortex and increased membrane tension at the TNT-connected sites. Additionally, TNT bending results in an elevation of intracellular calcium levels in TNT-connected cells, a response attenuated by gadolinium ions, a non-selective mechanosensitive calcium channel blocker . The degree of TNT deflection positively correlated with decreased actin cortex curvature and increased calcium levels. Furthermore, stretching TNT due to the separation of TNT-connected cells resulted in decreased actin cortex curvature and increased intracellular calcium in TNT-connected cells. The levels of these cellular responses depended on the length changes of TNTs. Moreover, TNT connections influence cell migration by regulating cell rotation, which involves the activation of mechanosensitive calcium channels . In conclusion, our study revealed the transmission of mechanical signals through TNTs and the subsequent responses of TNT-connected cells, highlighting a previously unrecognized communication function of TNTs. This research provides valuable insights into the role of TNTs in long-distance intercellular mechanical signaling .
研究领域:
细胞生物学
·
生物物理学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Shisheng Chen,Xueyang Ren,Jingfeng Xu,Yuehui Yuan,Jing Shi,Huaxu Ling,Yizhuo Yang,Wenjie Tang,Fangzhou Lu,Xiangqing Kong,Benhui Hu
A tactile sensor needs to perceive static pressures and dynamic forces in real-time with high accuracy for early diagnosis of diseases and development of intelligent medical prosthetics. However, biomechanical and external mechanical signals are always aliased (including variable physiological and pathological events and motion artifacts), bringing great challenges to precise identification of the signals of interest (SOI). Although the existing signal segmentation methods can extract SOI and remove artifacts by blind source separation and/or additional filters, they may restrict the recognizable patterns of the device, and even cause signal distortion. Herein, an in-memory tactile sensor (IMT) with a dynamically adjustable steep-slope region (SSR) and nanocavity-induced nonvolatility (retention time >1000 s) is proposed on the basis of a machano-gated transistor, which directly transduces the tactile stimuli to various dope states of the channel. The programmable SSR endows the sensor with a critical window of responsiveness, realizing the perception of signals on demand. Owing to the nonvolatility of the sensor, the mapping of mechanical cues with high spatiotemporal accuracy and associative learning between two physical inputs are realized, contributing to the accurate assessment of the tissue health status and ultralow-power (about 25.1 μW) identification of an occasionally occurring tremor.
研究领域:
生物医学工程
·
电子工程
·
材料科学
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DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Luzhong Zhang,Jingjing Wei,Yuan Huang,Luqi Wang,Huasong Gao,Yumin Yang
Spinal cord injury (SCI) is a devastating condition without effective therapy currently available. The inflammatory cascade following SCI leads to neuronal apoptosis and glial cell activation. The utilization of local injectable hydrogels with immunotherapy drugs directly into injured nerve tissues represents a promising therapeutic strategy. Herein, injectable hydrogels grafted with clickable methylprednisolone (MP) and cellular adhesion peptide were developed using free radical polymerization for promoting nerve regeneration following SCI. MP conjugated hydrogels could modulate the immunoinflammatory microenvironment of SCI and sustain neuron survival. The multi-stiffness hydrogels were fabricated by adjusting concentration ratios to evaluate appropriate mechanical stimuli. In a model of dorsal root ganglion, MP grafted hydrogels with mechanical signals similar to those of adult rat spinal cords demonstrated superior efficacy in promoting dorsal root ganglion growth. MP grafted hydrogels could regulate the immune-inflammatory microenvironment, promote recovery of both motor function and sensory functions. The positive findings suggested that the interplay between immunomodulation and mechanical signals plays a crucial role in promoting nerve regeneration, indicating significant potential for hydrogels as a therapeutic approach for repairing SCI.
研究领域:
生物医学工程
·
神经科学
·
免疫学
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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
·
生物材料
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Xue Bin,Xu Zhengyu,Li Lan,Guo Kaiqiang,Mi Jing,Wu Haipeng,Li Yiran,Xie Chunmei,Jin Jing,Xu Juan,Jiang Chunping,Gu Xiaosong,Qin Meng,Jiang Qing,Cao Yi,Wang Wei
Hydrogels are extensively utilized in stem cell-based tissue regeneration, providing a supportive environment that facilitates cell survival, differentiation, and integration with surrounding tissues. However, designing hydrogels for regenerating hard tissues like bone presents significant challenges. Here, we introduce macroporous hydrogels with spatiotemporally programmed mechanical properties for stem cell-driven bone regeneration. Using liquid-liquid phase separation and interfacial supramolecular self-assembly of protein fibres, the macroporous structure of hydrogels provide ample space to prevent contact inhibition during proliferation. The rigid protein fibre-coated pore shell provides sustained mechanical cues for guiding osteodifferentiation and protecting against mechanical loads. Temporally, the hydrogel exhibits tunable degradation rates that can synchronize with new tissue deposition to some extent. By integrating localized mechanical heterogeneity, macroporous structures, surface chemistry, and regenerative degradability, we demonstrate the efficacy of these stem cell-encapsulated hydrogels in rabbit and porcine models. This marks a substantial advancement in tailoring the mechanical properties of hydrogels for stem cell-assisted tissue regeneration.
研究领域:
组织工程
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再生医学
·
生物材料科学
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DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Yueyue Ma,Yadong He,Chenlong Hao,Xiang Li,Ling Li,Youwei Zhao,Yucang Zhang,Wenming Zhang
With the continuous development of self-powered sensing systems, achieving efficient energy self-supply and high-performance signal acquisition simultaneously has emerged as a main trend for next-generation sensors. However, developing functional materials for such sensing systems is still facing crucial challenges. Herein, a multifunctional MnO 2 @PANI (MP) composite material was designed to realize a synchronized “integration” strategy. Specifically, the MP serves as a cathode in photo-assisted zinc-ion batteries (PA-ZIBs), enabling solar energy conversion and storage. The p-n heterojunction formed between MnO 2 and PANI promotes effective separation of photogenerated electron-hole pairs and enhances Zn 2+ kinetics. Therefore, the PA-ZIBs deliver a high self-charging voltage of 1.08 V and 33 % enhancement in specific capacity (reaching 249.5 mAh g −1 at 0.1 A g −1 ) under illumination. Meanwhile, it also functions as the active layer of a flexible strain sensor, achieving efficient mechanical signal detection. The core–shell structure and composite component improve both structural stability and conductivity. As a result, the sensor exhibits high sensitivity, a fast response time of 0.4 s, and excellent durability over 2000 cycles. Furthermore, proof-of-concept demonstrations validate the device’s capability to simultaneously harvest solar energy and detect physiological signals. This work offers a new solution for designing self-powered sensing systems and intelligent healthcare applications by merging energy-autonomous operation with multifunctional sensing capabilities.
研究领域:
材料科学
·
能源技术
·
传感器技术
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Lin Niu,Yu-jie Lu,Xing-wang Zu,Wen Yang,Fu-kui Shen,Yan-yan Xu,Min Jiang,Yang Xie,Su-yun Li,Jie Gao,Gang Bai
Transient receptor potential vanilloid 4 (TRPV4) plays a role in regulating pulmonary fibrosis (PF). While several TRPV4 antagonists including magnolol (MAG), have been discovered, the mechanism of action is not fully understood. This study aimed to investigate the effect of MAG on alleviating fibrosis in chronic obstructive pulmonary disease (COPD) based on TRPV4, and to further analyze its mechanism of action on TRPV4. COPD was induced using cigarette smoke and LPS. The therapeutic effect of MAG on COPD-induced fibrosis was evaluated. TRPV4 was identified as the main target protein of MAG using target protein capture with MAG probe and drug affinity response target stability assay. The binding sites of MAG at TRPV4 were analyzed using molecular docking and small molecule interaction with TRPV4-ankyrin repeat domain (ARD). The effects of MAG on TRPV4 membrane distribution and channel activity were analyzed by co-immunoprecipitation, fluorescence co-localization, and living cell assay of calcium levels. By targeting TRPV4-ARD, MAG disrupted the binding between phosphatidylinositol 3 kinase γ and TRPV4, leading to hampered membrane distribution on fibroblasts. Additionally, MAG competitively impaired ATP binding to TRPV4-ARD, inhibiting TRPV4 channel opening activity. MAG effectively blocked the fibrotic process caused by mechanical or inflammatory signals, thus alleviating PF in COPD. Targeting TRPV4-ARD presents a novel treatment strategy for PF in COPD.
研究领域:
药理学
·
肺科学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Wenjie Zhang,Wenliang Xue,Zhaoli Jia,Rong Yang,Penghui Wang,Yi Hu,Xiaoyan Tan,Qiang Chen,Bo Chi
Regenerating damaged cartilage remains a challenge due to limited cell availability and inefficient chondrogenic differentiation. Here, we present a photo-driven dynamic hydrogel with a double-network structure to meet this challenge. The fabrication strategy involves a combination of a photosensitive host–guest network with a covalent network, providing tunable mechanical cues that effectively regulate bone marrow mesenchymal stem cells (BMSCs) behavior within their microenvironment while maintaining macroscopical stability. Employing a two-step stiffness-tunable process mediated by controlled low-dose light exposure, the hydrogel exerts precise control over BMSCs proliferation and orchestrates chondrogenic differentiation, leading to the upregulation of crucial chondrogenic genes, notably SOX9 and ACAN. Empirical evidence derived from histological analysis substantiates the functional efficacy of the hydrogel, confirming the regenerative potential of cartilage tissues. This study presents an innovative and promising strategy for stem cell culture, in vitro differentiation, and cell delivery, with implications for cartilage defect repair and tissue regeneration.
研究领域:
组织工程
·
干细胞生物学
·
生物医学材料
·
再生医学
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产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Genjiang Zheng,Chen Yang,Wei Yu,Ye Tian,Zeng Xu,Jia Liu,Shatong He,Yunhao Wang,Zhihao Yue,Xiaodong Wu,Hongyu Zhou,Bo Hu,Wei-En Yuan,Huajiang Chen
Paralysis resulting from spinal cord injury (SCI) arises from the limited regenerative capacity of axons. Mechanical factors have recently emerged as crucial regulators of axon regeneration, complementing or even surpassing chemical cues. In this study, we demonstrated that extracellular matrix stiffness, a key mechanical signal, not only modulated the regenerative capacity of neuronal axons in spinal cord with aging, but significantly fine-tuned axon pathfinding through negative-durotaxis pattern. So, it is imperative to develop a scaffold with biomimetic mechanical guidance properties to promote neural axon regeneration after SCI. Strikingly, inspired by the robust adhesive mechanism of mussels, we developed a facile strategy to synthesize catechol-modified HAMA hydrogel (HAMA@CA) that mimics native spinal cord tissue properties, effectively modulates the biomechanical microenvironment, enhances tissue–implant adhesion, and ultimately promotes spinal cord integration after SCI. Mechanistically, HAMA@CA hydrogel regulates neuronal axon pathfinding following a negative durotaxis pattern, coinciding with changes in mechanosensitive signaling and actomyosin contractility via the Piezo1/RhoA/MLC pathway. RNA-seq analysis also confirms mechanical-mediated SCI repairing by HAMA@CA. These results demonstrates that HAMA@CA rationally combined with mechanical and biochemical cues create promising tissue-engineered strategies to facilitate the repair of SCI. This innovative strategy holds significant promise for future clinical applications in the field.
研究领域:
神经科学
·
生物医学工程
·
组织工程
·
机械生物学
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Zhangwen Peng,Yunfei Yi,Yichu Nie,Tianqi Wang,Jia Tang,Sheng Hong,Yuanqi Liu,Wenxin Huang,Shengjie Sun,Hui Tan,Meiying Wu
The tumor develops defense tactics, including conversing the mechanical characteristics of tumor cells and their surrounding environment. A recent study reported that cholesterol depletion stiffens tumor cells, which could enhance adaptive T-cell immunotherapy. However, it remains unclear whether reducing the cholesterol in tumor cells contributes to re-educating the stiff tumor matrix, which serves as a physical barrier against drug penetration. Herein, we found that depleting cholesterol from tumor cells can demolish the intratumor physical barrier by disrupting the mechanical signal transduction between tumor cells and the extracellular matrix through the destruction of lipid rafts. This disruption allows nanoparticles (H/S@hNP) to penetrate deeply, resulting in improved photodynamic treatment. Our research also indicates that cholesterol depletion can inhibit the epithelial-mesenchymal transition and repolarize tumor-associated macrophages from M2 to M1, demonstrating the essential role of cholesterol in tumor progression. Overall, this study reveals that a cholesterol-depleted, softened tumor matrix reduces the difficulty of drug penetration, leading to enhanced antitumor therapeutics.
研究领域:
肿瘤学
·
生物物理学
·
免疫疗法
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Protein & Cell
·
2020
·Vol. 11
·期 4
·267-285
·
IF 10.164
Xu Gang,Ding Zhaozhao,Lu Qiang,Zhang Xiaoyi,Zhou Xiaozhong,Xiao Liying,Lu Guozhong,Kaplan David L
Gradient biomaterials are considered as preferable matrices for tissue engineering due to better simulation of native tissues. The introduction of gradient cues usually needs special equipment and complex process but is only effective to limited biomaterials. Incorporation of multiple gradients in the hydrogels remains challenges. Here, beta-sheet rich silk nanofibers (BSNF) were used as building blocks to introduce multiple gradients into different hydrogel systems through the joint action of crosslinking and electric field. The blocks migrated to the anode along the electric field and gradually stagnated due to the solution-hydrogel transition of the systems, finally achieving gradient distribution of the blocks in the formed hydrogels. The gradient distribution of the blocks could be tuned easily through changing different factors such as solution viscosity, which resulted in highly tunable gradient of mechanical cues. The blocks were also aligned under the electric field, endowing orientation gradient simultaneously. Different cargos could be loaded on the blocks and form gradient cues through the same crosslinking-electric field strategy. The building blocks could be introduced to various hydrogels such as Gelatin and NIPAM, indicating the universality. Complex niches with multiple gradient cues could be achieved through the strategy. Silk-based hydrogels with suitable mechanical gradients were fabricated to control the osteogenesis and chondrogenesis. Chondrogenic-osteogenic gradient transition was obtained, which stimulated the ectopic osteochondral tissue regeneration in vivo. The versatility and highly controllability of the strategy as well as multifunction of the building blocks reveal the applicability in complex tissue engineering and various interfacial tissues.
研究领域:
生物材料科学
·
组织工程
·
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）