Retained foreign objects in the abdomen and pelvis are serious clinical problems yet the imaging required can present difficulties. Prolonged retention of lipiodized oil used for hysterosalpingography over years is ve...Retained foreign objects in the abdomen and pelvis are serious clinical problems yet the imaging required can present difficulties. Prolonged retention of lipiodized oil used for hysterosalpingography over years is very rare. However, lipiodized oil had previously been misdiagnosed as residual metallic material. We are reporting a case in which the latest computed tomography (CT) equipment seemed inadequate for obtaining a clear pre-operative diagnosis. Here, we describe the case of a 33-year-old Japanese female whose pelvis had contained retained lipiodized oil that had been suspected as residual metallic material. The preoperative diagnosis was very difficult and included three-dimensional computed tomography (3D-CT) of unclear results despite expectations of resolution. By laparoscopic surgery, we removed a cyst of approximately 2 cm containing a yellowish oily fluid. Postoperatively, we demonstrated that the fluid was lipiodized oil. A postoperative experiment to attempt distinguishing lipiodized oil from metal through gemstone spectral CT imaging did not offer clarity either. Distinguishing between retained lipiodized oil and metallic material in the abdominal cavity may still present unexpected difficulties even with the latest medical equipments.展开更多
Existing biomimetic robots can perform some basic rat-like movement primitives(MPs)and simple behavior with stiff combinations of these MPs.To mimic typical rat behavior with high similarity,we propose parameterizing ...Existing biomimetic robots can perform some basic rat-like movement primitives(MPs)and simple behavior with stiff combinations of these MPs.To mimic typical rat behavior with high similarity,we propose parameterizing the behavior using a probabilistic model and movement characteristics.First,an analysis of fifteen 10 min video sequences revealed that an actual rat has six typical behaviors in the open field,and each kind of behavior contains different bio-inspired combinations of eight MPs.We used the softmax classifier to obtain the behavior-movement hierarchical probability model.Secondly,we specified the MPs using movement parameters that are static and dynamic.We obtained the predominant values of the static and dynamic movement parameters using hierarchical clustering and fuzzy C-means clustering,respectively.These predominant parameters were used for fitting the rat spinal joint trajectory using a second-order Fourier series,and the joint trajectory was generalized using a back propagation neural network with two hidden layers.Finally,the hierarchical probability model and the generalized joint trajectory were mapped to the robot as control policy and commands,respectively.We implemented the six typical behaviors on the robot,and the results show high similarity when compared with the behaviors of actual rats.展开更多
Recent advances in networked cooperative autonomous sys-tems offer the potential to significantly improve system quality for a wide range of applications.Progress in embedded processor,sensor,communication,and network...Recent advances in networked cooperative autonomous sys-tems offer the potential to significantly improve system quality for a wide range of applications.Progress in embedded processor,sensor,communication,and networking technology in the last few decades has accelerated interest in networked cooperative autonomous systems,multirobot systems,and distributed sensor networks for applications such as manufacturing,logistics,pro-cess monitoring,enhanced situational awareness,plant safety,inspection,security,and rescue operations.展开更多
Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. H...Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. However, the exact mechanism of added CAM has not been fully elucidated. This case report will provide helpful information for understanding the significance and the mechanism of action of CAM as an add-on therapy. Patient: A 78-year-old female patient with IgA-λ type MM was treated with low-dose Len coupled with low-dose Dex (low Rd), and excellent response was achieved for long term, but she later became refractory to this treatment. Then, CAM was added to low Rd (low Rd-CAM, i.e., modified BiRD therapy). This add-on-therapy was found to be effective, but later suspended because of pneumonitis. Then, low-dose Len coupled with CAM (low R-CAM) treatment was applied;but effect of this Dex-free treatment was insufficient. Thus, low Rd-CAM was reapplied and satisfactory reduction of IgA was achieved. This fact suggests that low Rd-CAM is the favorable combination, Dex is requisite and CAM might have enhanced the effect of Dex. In this case, various serum cytokines were examined during the course of illness. Only interleukin-6 showed apparent increase, and tumor necrosis factor-α, transforming growth factor-β, soluble IL-2 receptors and C-reactive protein showed the slight increase during low Rd-CAM treatment. The results seem somewhat conflicting, but it seems that intricate cytokine response due to immune activation might have occurred during low Rd-CAM treatment.展开更多
Computer-based simulations are essential for clarifying the hemodynamics of brain aneurysms. Since cerebrovascular disease is often fatal, it is strongly desirable to predict its progression. While previous studies ha...Computer-based simulations are essential for clarifying the hemodynamics of brain aneurysms. Since cerebrovascular disease is often fatal, it is strongly desirable to predict its progression. While previous studies have clarified the initiation mechanism of aneurysms, their growth mechanism remains unclear. Consequently, it is difficult to develop a diagnostic system for predicting aneurysm rupture. This study seeks to clarify the mechanism of aneurysm growth by identifying significant hydrodynamic factors. We focus on a single ruptured aneurysm that was followed up for five years. Computer simulations and fluid dynamic experiments with silicone vessel models were performed. To confirm the reliability of data in the computer simulations, we conducted particle image velocimetry measurements in steady flow. We then performed computer simulations for pulsatile conditions to determine an effective index for aneurysm growth. We obtained good agreement between the trends in the obtained computer simulation and experimental data. Numerical simulations for pulsatile flow in three models revealed that aneurysms grew in regions having a low wall shear stress, a low aneurysm formation indicator, and a high oscillatory shear index.展开更多
Bio-integrated microrobots(BIMs),which are fabricated with biofriendly materials,biological units(e.g.cells or biomolecules),or cell-material hybrids have emerged as a promising technology for minimally invasive biome...Bio-integrated microrobots(BIMs),which are fabricated with biofriendly materials,biological units(e.g.cells or biomolecules),or cell-material hybrids have emerged as a promising technology for minimally invasive biomedicine.The diminutive size and flexible structures enable BIMs to navigate within narrow,deep,and challenging-to-reach in vivo regions,performing biopsy,diagnostic,drug delivery,and therapeutic functions with minimal invasiveness.However,the clinical deployment of BIMs is a highly orchestrated task that requires consideration of material properties,structural design,locomotion,observation,therapeutic outcomes,and side effects on cells and tissues,etc.In this review,we review and discuss the latest advances in the biointegrated microrobot domain,evaluating various methods associated with materials,fabrication,actuation,and the implementation of biomedical functions in BIMs.By comparing the advantages and shortcomings of these techniques,this review highlights the challenges and future trends in highly intelligent bio-integrated microrobots,which have huge potential in minimally invasive biomedicine.展开更多
The evolution from passive nanoscale observation to active robotic manipulation represents a paradigm shift in humanity's quest tomaster matter at the atomic scale. This review systematically traces the historical...The evolution from passive nanoscale observation to active robotic manipulation represents a paradigm shift in humanity's quest tomaster matter at the atomic scale. This review systematically traces the historical and conceptual foundations of nanomanipulation,beginning with ancient atomic theory and culminating in Feynman's vision of deterministic atomic control.Nanomanipulation technologies can be categorized into three dimensions: observation (imaging and tracking), construction(assembly and fabrication), and operation (automation and control). This review critically examines transformative technologies—from optical tweezers and atomic force microscopy (AFM) to autonomous nanorobots in scanning electron microscopy (SEM)—highlighting their pivotal roles in overcoming diffraction limits, thermal noise, and quantum stochasticity. Innovations such asmachine learning-enhanced control, stochastic model predictive control, and biohybrid nanorobots underscore the transition fromscripted tasks to adaptive autonomy. However, persistent challenges—including the observer–constructor paradox, environmentalstochasticity, and scalability—necessitate interdisciplinary convergence of quantum metrology, neuromorphic computing, andethical frameworks. By bridging theoretical insights with practical applications, this review charts a roadmap for nanoroboticsystems to transcend laboratory confines, enabling breakthroughs in nanomedicine, quantum devices, and atomic-scalemanufacturing. The synthesis of embodied intelligence, distributed sensing, and edge quantum computing heralds a futurewhere nanomanipulation redefines the boundaries of science, engineering, and philosophy.展开更多
Potassium-ion batteries(PIBs)are considered promising alternatives to lithium-ion batteries owing to cost-effective potassium resources and a suitable redox potential of-2.93 V(vs.-3.04 V for Li+/Li).However,the explo...Potassium-ion batteries(PIBs)are considered promising alternatives to lithium-ion batteries owing to cost-effective potassium resources and a suitable redox potential of-2.93 V(vs.-3.04 V for Li+/Li).However,the exploration of appro-priate electrode materials with the correct size for reversibly accommodating large K+ions presents a significant challenge.In addition,the reaction mecha-nisms and origins of enhanced performance remain elusive.Here,tetragonal FeSe nanoflakes of different sizes are designed to serve as an anode for PIBs,and their live and atomic-scale potassiation/depotassiation mechanisms are revealed for the first time through in situ high-resolution transmission electron micros-copy.We found that FeSe undergoes two distinct structural evolutions,sequen-tially characterized by intercalation and conversion reactions,and the initial intercalation behavior is size-dependent.Apparent expansion induced by the intercalation of K+ions is observed in small-sized FeSe nanoflakes,whereas unexpected cracks are formed along the direction of ionic diffusion in large-sized nanoflakes.The significant stress generation and crack extension originating from the combined effect of mechanical and electrochemical interactions are elucidated by geometric phase analysis and finite-element analysis.Despite the different intercalation behaviors,the formed products of Fe and K_(2)Se after full potassiation can be converted back into the original FeSe phase upon depotassiation.In particular,small-sized nanoflakes exhibit better cycling perfor-mance with well-maintained structural integrity.This article presents the first successful demonstration of atomic-scale visualization that can reveal size-dependent potassiation dynamics.Moreover,it provides valuable guidelines for optimizing the dimensions of electrode materials for advanced PIBs.展开更多
Cyborg and Bionic Systems provides a much-needed forum for presenting research outcomes and insights in various fields concerning living-robotics hybrid systems.The research efforts within these fields are aimed at un...Cyborg and Bionic Systems provides a much-needed forum for presenting research outcomes and insights in various fields concerning living-robotics hybrid systems.The research efforts within these fields are aimed at understanding,mimicking,and recapitulating natural principles and mechanisms of life,which have inspired numerous inventions and propelled technology advancements throughout history.From cardiac pacemakers to artificial cochlea,a range of biomedical applications of cyborg and bionic system technologies has benefited humans.Artificial organs,exoskeletons with neural interfacing,and brain-machine interfaces(BMIs)for neurological recovery have been applied to replace or repair lost functions.An example of inspiring achievements and the potential of cyborg and bionic system technologies to restore human capabilities is CYBATHLON,a championship for physically challenged people using assistive technologies which began in 2016.These technologies are closely coupled with the“embodiment”issues which are essentially concerned with the psychological and sensing aspects of prosthetic arms and legs and even extra artificial limbs to augment our body for carrying out various tasks,a concept championed by a pioneering team led by Professor Harry Asada at MIT through a technology aptly named Supernumerary Robotic Limbs(SRL).展开更多
Engineered extracellular matrices(ECMs)that replicate complex in-vivo features have shown great potential in tissue engineering.Biocompatible hydrogel microstructures have been widely used to replace these native ECMs...Engineered extracellular matrices(ECMs)that replicate complex in-vivo features have shown great potential in tissue engineering.Biocompatible hydrogel microstructures have been widely used to replace these native ECMs for physiologically relevant research.However,accurate reproduction of the 3D hierarchical and nonuniform mechanical stffness inside one integrated microstructure to mimic the complex mechanical properties of native ECMs presents a major challenge.Here,by using digital holographic microscopy(DHM)-based stffness imaging feedback,we propose a novel closed-loop control algorithm to achieve high-accuracy control of mechanical properties for hydrogel microstructures that recapitulate the physiological properties of native ECMs with high fidelity.During photoprinting,the photocuring area of the hydrogel is divided into microscale grid areas to locally control the photocuring process.With the assistance of a motorized microfluidic channel,the curing thickness is controlled with layer-by-layer stacking.The DHM-based stiffness imaging feedback allows accurate adjustment of the photocuring degree in every grid area to change the crosslinking network density of the hydrogel,thus enabling large-span and high-resolution modulation of mechanical properties.Finally,the gelatin methacrylate was used as a typical biomaterial to construct the highfidelity biomimetic ECMs.The Young's modulus could be flexibly modulated in the 10 kPa to 50 kPa range.Additionally,the modulus gradient was accurately controlled to within 2.9 kPa.By engineering ECM with locally different mechanical properties,cell spreading along the stff areas was observed successfully.We believe that this method can regenerate complex biomimetic ECMs that closely recapitulate in-vivo mechanical properties for further applications in tissue engineering and biomedical research.展开更多
文摘Retained foreign objects in the abdomen and pelvis are serious clinical problems yet the imaging required can present difficulties. Prolonged retention of lipiodized oil used for hysterosalpingography over years is very rare. However, lipiodized oil had previously been misdiagnosed as residual metallic material. We are reporting a case in which the latest computed tomography (CT) equipment seemed inadequate for obtaining a clear pre-operative diagnosis. Here, we describe the case of a 33-year-old Japanese female whose pelvis had contained retained lipiodized oil that had been suspected as residual metallic material. The preoperative diagnosis was very difficult and included three-dimensional computed tomography (3D-CT) of unclear results despite expectations of resolution. By laparoscopic surgery, we removed a cyst of approximately 2 cm containing a yellowish oily fluid. Postoperatively, we demonstrated that the fluid was lipiodized oil. A postoperative experiment to attempt distinguishing lipiodized oil from metal through gemstone spectral CT imaging did not offer clarity either. Distinguishing between retained lipiodized oil and metallic material in the abdominal cavity may still present unexpected difficulties even with the latest medical equipments.
基金supported in part by the National Natural Science Foundation of China(62022014)in part by the National Key Research and Development Program of China(2017YFE0117000)。
文摘Existing biomimetic robots can perform some basic rat-like movement primitives(MPs)and simple behavior with stiff combinations of these MPs.To mimic typical rat behavior with high similarity,we propose parameterizing the behavior using a probabilistic model and movement characteristics.First,an analysis of fifteen 10 min video sequences revealed that an actual rat has six typical behaviors in the open field,and each kind of behavior contains different bio-inspired combinations of eight MPs.We used the softmax classifier to obtain the behavior-movement hierarchical probability model.Secondly,we specified the MPs using movement parameters that are static and dynamic.We obtained the predominant values of the static and dynamic movement parameters using hierarchical clustering and fuzzy C-means clustering,respectively.These predominant parameters were used for fitting the rat spinal joint trajectory using a second-order Fourier series,and the joint trajectory was generalized using a back propagation neural network with two hidden layers.Finally,the hierarchical probability model and the generalized joint trajectory were mapped to the robot as control policy and commands,respectively.We implemented the six typical behaviors on the robot,and the results show high similarity when compared with the behaviors of actual rats.
文摘Recent advances in networked cooperative autonomous sys-tems offer the potential to significantly improve system quality for a wide range of applications.Progress in embedded processor,sensor,communication,and networking technology in the last few decades has accelerated interest in networked cooperative autonomous systems,multirobot systems,and distributed sensor networks for applications such as manufacturing,logistics,pro-cess monitoring,enhanced situational awareness,plant safety,inspection,security,and rescue operations.
文摘Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. However, the exact mechanism of added CAM has not been fully elucidated. This case report will provide helpful information for understanding the significance and the mechanism of action of CAM as an add-on therapy. Patient: A 78-year-old female patient with IgA-λ type MM was treated with low-dose Len coupled with low-dose Dex (low Rd), and excellent response was achieved for long term, but she later became refractory to this treatment. Then, CAM was added to low Rd (low Rd-CAM, i.e., modified BiRD therapy). This add-on-therapy was found to be effective, but later suspended because of pneumonitis. Then, low-dose Len coupled with CAM (low R-CAM) treatment was applied;but effect of this Dex-free treatment was insufficient. Thus, low Rd-CAM was reapplied and satisfactory reduction of IgA was achieved. This fact suggests that low Rd-CAM is the favorable combination, Dex is requisite and CAM might have enhanced the effect of Dex. In this case, various serum cytokines were examined during the course of illness. Only interleukin-6 showed apparent increase, and tumor necrosis factor-α, transforming growth factor-β, soluble IL-2 receptors and C-reactive protein showed the slight increase during low Rd-CAM treatment. The results seem somewhat conflicting, but it seems that intricate cytokine response due to immune activation might have occurred during low Rd-CAM treatment.
文摘Computer-based simulations are essential for clarifying the hemodynamics of brain aneurysms. Since cerebrovascular disease is often fatal, it is strongly desirable to predict its progression. While previous studies have clarified the initiation mechanism of aneurysms, their growth mechanism remains unclear. Consequently, it is difficult to develop a diagnostic system for predicting aneurysm rupture. This study seeks to clarify the mechanism of aneurysm growth by identifying significant hydrodynamic factors. We focus on a single ruptured aneurysm that was followed up for five years. Computer simulations and fluid dynamic experiments with silicone vessel models were performed. To confirm the reliability of data in the computer simulations, we conducted particle image velocimetry measurements in steady flow. We then performed computer simulations for pulsatile conditions to determine an effective index for aneurysm growth. We obtained good agreement between the trends in the obtained computer simulation and experimental data. Numerical simulations for pulsatile flow in three models revealed that aneurysms grew in regions having a low wall shear stress, a low aneurysm formation indicator, and a high oscillatory shear index.
基金funded by the National Natural Science Foundation of China under Grant Nos.62222305,62403056,62088101the Science and Technology Innovation Program of Beijing Institute of Technology under Grant 2024CX06008the Postdoctoral Fellowship Program of CPSF under Grant BX20230459.
文摘Bio-integrated microrobots(BIMs),which are fabricated with biofriendly materials,biological units(e.g.cells or biomolecules),or cell-material hybrids have emerged as a promising technology for minimally invasive biomedicine.The diminutive size and flexible structures enable BIMs to navigate within narrow,deep,and challenging-to-reach in vivo regions,performing biopsy,diagnostic,drug delivery,and therapeutic functions with minimal invasiveness.However,the clinical deployment of BIMs is a highly orchestrated task that requires consideration of material properties,structural design,locomotion,observation,therapeutic outcomes,and side effects on cells and tissues,etc.In this review,we review and discuss the latest advances in the biointegrated microrobot domain,evaluating various methods associated with materials,fabrication,actuation,and the implementation of biomedical functions in BIMs.By comparing the advantages and shortcomings of these techniques,this review highlights the challenges and future trends in highly intelligent bio-integrated microrobots,which have huge potential in minimally invasive biomedicine.
基金funding support from the Funds for the National Key Research and Development Program(2023YFF0721400)National Natural Science Foundation of China under Grant 62127810.The anonymous reviewers'constructive comments on our initial draft were invaluable in shaping this final version.
文摘The evolution from passive nanoscale observation to active robotic manipulation represents a paradigm shift in humanity's quest tomaster matter at the atomic scale. This review systematically traces the historical and conceptual foundations of nanomanipulation,beginning with ancient atomic theory and culminating in Feynman's vision of deterministic atomic control.Nanomanipulation technologies can be categorized into three dimensions: observation (imaging and tracking), construction(assembly and fabrication), and operation (automation and control). This review critically examines transformative technologies—from optical tweezers and atomic force microscopy (AFM) to autonomous nanorobots in scanning electron microscopy (SEM)—highlighting their pivotal roles in overcoming diffraction limits, thermal noise, and quantum stochasticity. Innovations such asmachine learning-enhanced control, stochastic model predictive control, and biohybrid nanorobots underscore the transition fromscripted tasks to adaptive autonomy. However, persistent challenges—including the observer–constructor paradox, environmentalstochasticity, and scalability—necessitate interdisciplinary convergence of quantum metrology, neuromorphic computing, andethical frameworks. By bridging theoretical insights with practical applications, this review charts a roadmap for nanoroboticsystems to transcend laboratory confines, enabling breakthroughs in nanomedicine, quantum devices, and atomic-scalemanufacturing. The synthesis of embodied intelligence, distributed sensing, and edge quantum computing heralds a futurewhere nanomanipulation redefines the boundaries of science, engineering, and philosophy.
基金This work was supported by the National Key R&D Program of China(Grant No.2018YFB1304902)the National Natural Science Foundation of China(Grant Nos.12004034,U1813211,22005247,11904372,51502007,52072323,52122211,12174019,and 51972058)+1 种基金the Gen-eral Research Fund of Hong Kong(Project No.11217221)China Postdoctoral Science Foundation Funded Project(Grant No.2021M690386).
文摘Potassium-ion batteries(PIBs)are considered promising alternatives to lithium-ion batteries owing to cost-effective potassium resources and a suitable redox potential of-2.93 V(vs.-3.04 V for Li+/Li).However,the exploration of appro-priate electrode materials with the correct size for reversibly accommodating large K+ions presents a significant challenge.In addition,the reaction mecha-nisms and origins of enhanced performance remain elusive.Here,tetragonal FeSe nanoflakes of different sizes are designed to serve as an anode for PIBs,and their live and atomic-scale potassiation/depotassiation mechanisms are revealed for the first time through in situ high-resolution transmission electron micros-copy.We found that FeSe undergoes two distinct structural evolutions,sequen-tially characterized by intercalation and conversion reactions,and the initial intercalation behavior is size-dependent.Apparent expansion induced by the intercalation of K+ions is observed in small-sized FeSe nanoflakes,whereas unexpected cracks are formed along the direction of ionic diffusion in large-sized nanoflakes.The significant stress generation and crack extension originating from the combined effect of mechanical and electrochemical interactions are elucidated by geometric phase analysis and finite-element analysis.Despite the different intercalation behaviors,the formed products of Fe and K_(2)Se after full potassiation can be converted back into the original FeSe phase upon depotassiation.In particular,small-sized nanoflakes exhibit better cycling perfor-mance with well-maintained structural integrity.This article presents the first successful demonstration of atomic-scale visualization that can reveal size-dependent potassiation dynamics.Moreover,it provides valuable guidelines for optimizing the dimensions of electrode materials for advanced PIBs.
文摘Cyborg and Bionic Systems provides a much-needed forum for presenting research outcomes and insights in various fields concerning living-robotics hybrid systems.The research efforts within these fields are aimed at understanding,mimicking,and recapitulating natural principles and mechanisms of life,which have inspired numerous inventions and propelled technology advancements throughout history.From cardiac pacemakers to artificial cochlea,a range of biomedical applications of cyborg and bionic system technologies has benefited humans.Artificial organs,exoskeletons with neural interfacing,and brain-machine interfaces(BMIs)for neurological recovery have been applied to replace or repair lost functions.An example of inspiring achievements and the potential of cyborg and bionic system technologies to restore human capabilities is CYBATHLON,a championship for physically challenged people using assistive technologies which began in 2016.These technologies are closely coupled with the“embodiment”issues which are essentially concerned with the psychological and sensing aspects of prosthetic arms and legs and even extra artificial limbs to augment our body for carrying out various tasks,a concept championed by a pioneering team led by Professor Harry Asada at MIT through a technology aptly named Supernumerary Robotic Limbs(SRL).
基金the National Key R&D Program of China(2017YFE011700)the National Natural Science Foundation of China(62073042,62088101)。
文摘Engineered extracellular matrices(ECMs)that replicate complex in-vivo features have shown great potential in tissue engineering.Biocompatible hydrogel microstructures have been widely used to replace these native ECMs for physiologically relevant research.However,accurate reproduction of the 3D hierarchical and nonuniform mechanical stffness inside one integrated microstructure to mimic the complex mechanical properties of native ECMs presents a major challenge.Here,by using digital holographic microscopy(DHM)-based stffness imaging feedback,we propose a novel closed-loop control algorithm to achieve high-accuracy control of mechanical properties for hydrogel microstructures that recapitulate the physiological properties of native ECMs with high fidelity.During photoprinting,the photocuring area of the hydrogel is divided into microscale grid areas to locally control the photocuring process.With the assistance of a motorized microfluidic channel,the curing thickness is controlled with layer-by-layer stacking.The DHM-based stiffness imaging feedback allows accurate adjustment of the photocuring degree in every grid area to change the crosslinking network density of the hydrogel,thus enabling large-span and high-resolution modulation of mechanical properties.Finally,the gelatin methacrylate was used as a typical biomaterial to construct the highfidelity biomimetic ECMs.The Young's modulus could be flexibly modulated in the 10 kPa to 50 kPa range.Additionally,the modulus gradient was accurately controlled to within 2.9 kPa.By engineering ECM with locally different mechanical properties,cell spreading along the stff areas was observed successfully.We believe that this method can regenerate complex biomimetic ECMs that closely recapitulate in-vivo mechanical properties for further applications in tissue engineering and biomedical research.