Engineered microstructures that mimic in vivo tissues have demonstrated great potential for applications in regenerative medicine,drug screening,and cell behavior exploration.However,current methods for engineering mi...Engineered microstructures that mimic in vivo tissues have demonstrated great potential for applications in regenerative medicine,drug screening,and cell behavior exploration.However,current methods for engineering microstructures that mimic the multi-extracellular matrix and multicellular features of natural tissues to realize tissue-mimicking microstructures in vitro remain insufficient.Here,we propose a versatile method for constructing tissue-mimicking heterogeneous microstructures by orderly integration of macroscopic hydrogel exchange,microscopic cell manipulation,and encapsulation modulation.First,various cell-laden hydrogel droplets are manipulated at the millimeter scale using electrowetting on dielectric to achieve efficient hydrogel exchange.Second,the cells are manipulated at the micrometer scale using dielectrophoresis to adjust their density and arrangement within the hydrogel droplets.Third,the photopolymerization of these hydrogel droplets is triggered in designated regions by dynamically modulating the shape and position of the excitation ultraviolet beam.Thus,heterogeneous microstructures with different extracellular matrix geometries and components were constructed,including specific cell densities and patterns.The resulting heterogeneous microstructure supported long-term culture of hepatocytes and fibroblasts with high cell viability(over 90%).Moreover,the density and distribution of the 2 cell types had significant effects on the cell proliferation and urea secretion.We propose that our method can lead to the construction of additional biomimetic heterogeneous microstructures with unprecedented potential for use in future tissue engineering applications.展开更多
Flexible miniature robots are expected to enter difficult-to-reach areas in vivo to carry out targeted operations,attracting widespread attention.However,it is challenging for the existing soft miniature robots to sub...Flexible miniature robots are expected to enter difficult-to-reach areas in vivo to carry out targeted operations,attracting widespread attention.However,it is challenging for the existing soft miniature robots to substantially alter their stable shape once the structure is designed.This limitation leads to a fixed motion mode,which subsequently restricts their operating environment.In this study,we designed a biocompatible flexible miniature robot with a variable stable form that is capable of adapting to complex terrain environments through multiple movement modes.Inspired by the reversible stretching reaction of alginate saline gel stimulated by changes in environmental ion concentration,we manufactured a morphologically changeable super-soft hydrogel miniature robot body.According to the stretch and contraction shapes of the flexible hydrogel miniature robot,we designed magnetic fields for swing and rolling motion modes to realize multishape movement.The experimental results demonstrate that the deflection angle of the designed flexible miniature robot is reversible and can reach a maximum of 180°.The flexible miniature robot can complete forward swinging in the bar stretch state and tumbling motion in the spherical state.We anticipate that flexible hydrogel miniature robots with multiple morphologies and multimodal motion have great potential for biomedical applications in complex,unstructured,and enclosed living environments.展开更多
基金supported by the National Key Research and Development Program of China under grant 2023YFB4705400the National Natural Science Foundation of China under grant number 62222305,U22A2064+1 种基金the Beijing Natural Science Foundation under grant 4232055the Fundamental Research Program of Shanxi Province 20210302124033.
文摘Engineered microstructures that mimic in vivo tissues have demonstrated great potential for applications in regenerative medicine,drug screening,and cell behavior exploration.However,current methods for engineering microstructures that mimic the multi-extracellular matrix and multicellular features of natural tissues to realize tissue-mimicking microstructures in vitro remain insufficient.Here,we propose a versatile method for constructing tissue-mimicking heterogeneous microstructures by orderly integration of macroscopic hydrogel exchange,microscopic cell manipulation,and encapsulation modulation.First,various cell-laden hydrogel droplets are manipulated at the millimeter scale using electrowetting on dielectric to achieve efficient hydrogel exchange.Second,the cells are manipulated at the micrometer scale using dielectrophoresis to adjust their density and arrangement within the hydrogel droplets.Third,the photopolymerization of these hydrogel droplets is triggered in designated regions by dynamically modulating the shape and position of the excitation ultraviolet beam.Thus,heterogeneous microstructures with different extracellular matrix geometries and components were constructed,including specific cell densities and patterns.The resulting heterogeneous microstructure supported long-term culture of hepatocytes and fibroblasts with high cell viability(over 90%).Moreover,the density and distribution of the 2 cell types had significant effects on the cell proliferation and urea secretion.We propose that our method can lead to the construction of additional biomimetic heterogeneous microstructures with unprecedented potential for use in future tissue engineering applications.
基金supported by the National Key Research and Development Program of China under grant 2023YFB4705400the Beijing Natural Science Foundation under grant 4232055+1 种基金the National Natural Science Foundation of China under grant numbers 62073042,62222305,U22A2064,and 62088101the Science and Technology Innovation Program of Beijing Institute of Technology under grant 2022CX01019.
文摘Flexible miniature robots are expected to enter difficult-to-reach areas in vivo to carry out targeted operations,attracting widespread attention.However,it is challenging for the existing soft miniature robots to substantially alter their stable shape once the structure is designed.This limitation leads to a fixed motion mode,which subsequently restricts their operating environment.In this study,we designed a biocompatible flexible miniature robot with a variable stable form that is capable of adapting to complex terrain environments through multiple movement modes.Inspired by the reversible stretching reaction of alginate saline gel stimulated by changes in environmental ion concentration,we manufactured a morphologically changeable super-soft hydrogel miniature robot body.According to the stretch and contraction shapes of the flexible hydrogel miniature robot,we designed magnetic fields for swing and rolling motion modes to realize multishape movement.The experimental results demonstrate that the deflection angle of the designed flexible miniature robot is reversible and can reach a maximum of 180°.The flexible miniature robot can complete forward swinging in the bar stretch state and tumbling motion in the spherical state.We anticipate that flexible hydrogel miniature robots with multiple morphologies and multimodal motion have great potential for biomedical applications in complex,unstructured,and enclosed living environments.
