Chitosan(CS)-based nanocomposites have been studied in various fields,requiring a more facile and efficient technique to fabricate nanoparticles with customized structures.In this study,Ag@methacrylamide CS/poly(ethyl...Chitosan(CS)-based nanocomposites have been studied in various fields,requiring a more facile and efficient technique to fabricate nanoparticles with customized structures.In this study,Ag@methacrylamide CS/poly(ethylene glycol)diacrylate(Ag@MP)micropatterns are successfully fabricated by femtosecond laser maskless optical projection lithography(Fs-MOPL)for the first time.The formation mechanism of core-shell nanomaterial is demonstrated by the local surface plasmon resonances and the nucleation and growth theory.Amino and hydroxyl groups greatly affect the number of Ag@MP nanocomposites,which is further verified by replacing MCS with methacrylated bovine serum albumin and hyaluronic acid methacryloyl,respectively.Besides,the performance of the surface-enhanced Raman scattering,cytotoxicity,cell proliferation,and antibacterial was investigated on Ag@MP micropatterns.Therefore,the proposed protocol to prepare hydrogel core-shell micropattern by the home-built Fs-MOPL technique is prospective for potential applications in the biomedical and biotechnological fields,such as biosensors,cell imaging,and antimicrobial.展开更多
Over the course of millions of years,nature has evolved to ensure survival and presents us with a myriad of functional surfaces and structures that can boast high efficiency,multifunctionality,and sustainability.What ...Over the course of millions of years,nature has evolved to ensure survival and presents us with a myriad of functional surfaces and structures that can boast high efficiency,multifunctionality,and sustainability.What makes these surfaces particularly practical and effective is the intricate micropatterning that enables selective interactions with microstructures.Most of these structures have been realized in the laboratory environment using numerous fabrication techniques by tailoring specific surface properties.Of the available manufacturing methods,additive manufacturing(AM)has created opportunities for fabricating these structures as the complex architectures of the naturally occurring microstructures far exceed the traditional ways.This paper presents a concise overview of the fundamentals of such patterned microstructured surfaces,their fabrication techniques,and diverse applications.A comprehensive evaluation of micro fabrication methods is conducted,delving into their respective strengths and limitations.Greater emphasis is placed on AM processes like inkjet printing and micro digital light projection printing due to the intrinsic advantages of these processes to additively fabricate high resolution structures with high fidelity and precision.The paper explores the various advancements in these processes in relation to their use in microfabrication and also presents the recent trends in applications like the fabrication of microlens arrays,microneedles,and tissue scaffolds.展开更多
Cells are highly sensitive to their geometrical and mechanical microenvironment that directly regulate cell shape,cytoskeleton and organelle,as well as the nucleus morphology and genetic expression.The emerging two-di...Cells are highly sensitive to their geometrical and mechanical microenvironment that directly regulate cell shape,cytoskeleton and organelle,as well as the nucleus morphology and genetic expression.The emerging two-dimensional micropatterning techniques offer powerful tools to construct controllable and well-organized microenvironment for single-cell level investigations with qualitative analysis,cellular standardization,and in vivo environment mimicking.Here,we provide an overview of the basic principle and characteristics of the two most widely-used micropatterning techniques,including photolithographic micropatterning and soft lithography micropatterning.Moreover,we summarize the application of micropatterning technique in controlling cytoskeleton,cell migration,nucleus and gene expression,as well as intercellular communication.展开更多
Nerve conduits have been a viable alternative to the ‘gold standard’ autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffectiv...Nerve conduits have been a viable alternative to the ‘gold standard’ autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion （DRG） cells on poly（lactic-co-glycolic acid） （PLGA） films has not been previously conducted. Photolithography and micro-molding were used to define various combinations of ridge/groove dimensions on PLGA films. The DRG cells obtained from chicken embryos were cultured on micropatterned PLGA films for cell orientation and migration evaluation.Biodegradation of the films occurred during the test period, however, this did not cause deformation or distortion of the micropatterns. Results from the DRG cell orientation test suggest that when the ridge/groove ratio equals 1 （ridge/groove width parameters are equal, i.e., 10 μm/10 μm （even））, the degree of alignment depends on the size of the ridges and grooves, when the ratio is smaller than 1 （groove controlled） the alignment increases as the ridge size decreases, and when the ratio is larger than 1 （ridge controlled）, the alignment is reduced as the width of the grooves decreases. The migration rate and neurite extension of DRG neurons were greatest on 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films. Based on the data, the 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films are the optimized ridge/groove surface patterns for the construction of nerve repair devices.展开更多
After decades of research,peripheral nerve injury and repair still frequently results in paralysis,chronic pain and neuropathies leading to severe disability in patients.Current clinically available nerve conduits onl...After decades of research,peripheral nerve injury and repair still frequently results in paralysis,chronic pain and neuropathies leading to severe disability in patients.Current clinically available nerve conduits only provide crude guidance of regenerating axons across nerve gap without additional functionality.FK506（Tacrolimus）,an FDA approved immunosuppressant,has been shown to enhance peripheral nerve regeneration but carries harsh side-effects when delivered systemically.The objective of this study was to develop and evaluate a bioresorbable drug delivery system capable of local extended delivery of FK506 that also provides topological guidance cues to guide axon growth via microgrooves.Photolithography was used to create micropatterned poly（lactide-co-glycolic acid）（PLGA） films embedded with FK506.Non-patterned,10/10 μm（ridge/groove width）,and 30/30 μm patterned films loaded with 0,1,and 3 μg/cm2 FK506 were manufactured and characterized.In vitro FK506 rate of release testing indicated that the films are capable of an extended（at least 56 days）,controlled,and scalable release of FK506.Neurite extension bioactivity assay indicated that FK506 released from the films（concentration of samples tested ranged between 8.46–19.7 ng/m L） maintained its neural bioactivity and promoted neurite extension similar to control FK506 dosages（10 ng/m L FK506）.The multi-functional FK506 embedded,micropatterned poly（lactide-co-glycolic acid） films developed in this study have potential to be used in the construction of peripheral nerve repair devices.展开更多
Actin cytoskeleton plays crucial roles in various cellular functions.Extracellular matrix(ECM)can modulate cell morphology by remodeling the internal cytoskeleton.To define how geometry of ECM regulates the organizati...Actin cytoskeleton plays crucial roles in various cellular functions.Extracellular matrix(ECM)can modulate cell morphology by remodeling the internal cytoskeleton.To define how geometry of ECM regulates the organization of actin cytoskeleton,we plated individual NIH 3T3 cells on micropatterned substrates with distinct shapes and sizes.It was found that the stress fibers could form along the nonadhesive edges of T-shaped pattern,but were absent from the opening edge of V-shaped pattern,indicating that the organization of actin cytoskeleton was dependent on the mechanical environment.Furthermore,a secondary actin ring was observed on 50μm circular pattern while did not appear on 30μm and 40μm pattern,showing a size-dependent organization of actin cytoskeleton.Finally,osteoblasts,MDCK and A549 cells exhibited distinct organization of actin cytoskeleton on T-shaped pattern,suggesting a cell-type specificity in arrangement of actin cytoskeleton.Together,our findings brought novel insight into the organization of actin cytoskeleton on micropatterned environments.展开更多
Poly(ε-caprolactone)(PCL)holds unique bioresorbability and competent biomechanical properties for tissueengineering application.However,PCL is hydrophobic intrinsically and poor in cell-biomaterial interaction.In thi...Poly(ε-caprolactone)(PCL)holds unique bioresorbability and competent biomechanical properties for tissueengineering application.However,PCL is hydrophobic intrinsically and poor in cell-biomaterial interaction.In this study,we prepared a composite based on PCL and bioactive tantalum(Ta)to understand the effects of direct laser micropatterning on composite surface properties.The PCL/Ta composite after preparation was surface-patterned by femtosecond laser and characterized with surface morphology,crystal structure,chemical composition,wettability and cellular response of fibroblast.It was found that laser micropatterning enlarged the difference of wetting properties(~15°)on PCL and PCL/Ta surfaces.The wetting changes was dependent on both material composition and lasermachined geometry.The blending of Ta enhanced surface wettability with prolonged contact time on the laser-machined line and rectangle microarrays.In vitro culture results showed beneficial effects of laser micropatterning on cell morphology of the fibroblasts.On the PCL/Ta surfaces with line and rectangle microarrays,the cells were more likely to bridge the sidewalls of the microgrooves,showing adaptive 3D morphologies to the micro/nano topographies on the sidewalls.These findings are envisaged to facilitate surface design and micropattern optimization for favorable tuning the cell response to biomedical PCL/Ta composites.展开更多
Flower petals have not only diverse macroscopic morphologies but are rich in microscopic surface patterns, which are crucial to their biological functions. Both experimental measurements and theoretical analysis are c...Flower petals have not only diverse macroscopic morphologies but are rich in microscopic surface patterns, which are crucial to their biological functions. Both experimental measurements and theoretical analysis are conducted to reveal the physical mechanisms underlying the formation of minute wrinkles on flower petals. Three representative flowers, daisy, kalanchoe blossfeldiana, and Eustoma grandiflorurn, are investigated as examples. A surface wrinkling model, incorporating the measured mechanical properties and growth ratio, is used to elucidate the difference in their surface morphologies. The mismatch between the anisotropic epidermal cell growth and the isotropic secretion of surficial wax is found to dictate the surface patterns.展开更多
Here, we demonstrate an in-situ growth of micropatterned silver nanospheres(Ag NS) array on transparent polyimide(PI), namely PI-Ag substrate, applied as a flexible platform for metal-enhanced fluorescence(MEF). The s...Here, we demonstrate an in-situ growth of micropatterned silver nanospheres(Ag NS) array on transparent polyimide(PI), namely PI-Ag substrate, applied as a flexible platform for metal-enhanced fluorescence(MEF). The scheme proposed here can easily control the grid formation of Ag NSs and the particle size inside, thus achieving patterned fluorescence imaging and MEF efficiency optimization. Meanwhile, the magnitude of enhanced intensity, relying on the distance between Ag NSs and emissive molecules, was systematically investigated by exploring diverse polyethyleneimine(PEI) spacer thickness. Consequently,an optimal enhancement factor of 7.9 and a pattern of grid fluorescence imaging was obtained with an insertion of 10 nm PEI on the PI-Ag(25 nm) platform. Moreover, owing to robust adhesion between Ag NSs and PI film by in-situ growth, this flexible PI-Ag MEF platform maintained a stable MEF efficiency even after taking mechanical bending for 1000 cycles. This new surface-confined micropatterned Ag NSs PI film provides a promising candidate in design flexible MEF platforms for future analytical and clinical sensing applications.展开更多
Mitochondrial network architecture,which is closely related to mitochondrial function,is mechanically sensitive and regulated by multiple stimuli.However,the effects of microtopographic cues on mitochondria remain poo...Mitochondrial network architecture,which is closely related to mitochondrial function,is mechanically sensitive and regulated by multiple stimuli.However,the effects of microtopographic cues on mitochondria remain poorly defined.Herein,polycaprolactone(PCL)surfaces were used as models to investigate how micropatterns regulate mitochondrial network architecture and function in rat adipose-derived stem cells(rASCs).It was found that large pit(LP)-induced rASCs to form larger and more complex mitochondrial networks.Consistently,the expression of key genes related to mitochondrial dynamics revealed that mitochondrial fusion(MFN1 and MFN2)and midzone fission(DRP1 and MFF)were increased in rASCs on LP.In contrast,the middle pit(MP)-enhanced mitochondrial biogenesis,as evidenced by the larger mitochondrial area and higher expression of PGC-1.Both LP and MP promoted ATP production in rASCs.It is likely that LP increased ATP levels through modulating mitochondrial network architecture while MP stimulated mitochondria biogenesis to do so.Our study clarified the regulation of micropatterned surfaces on mitochondria,highlighting the potential of LP and MP as a simple platform to stimulate mitochondria and the subsequent cellular function of MSCs.展开更多
Cell migration influences many normal and pathological processes and is one of key issues addressed in cancer research studies.In this report,a plasma patterned polydimethylsiloxane(PDMS)substrate was used to selectiv...Cell migration influences many normal and pathological processes and is one of key issues addressed in cancer research studies.In this report,a plasma patterned polydimethylsiloxane(PDMS)substrate was used to selectively position hepatocarcinoma cells in order to characterize their migration behavior.We observed that cell mobility was directly related to the differentiation stage of the cells,with poorly-differentiated(SK-Hep-1)cells exhibiting higher mobility that well-differentiated(Hep-G2)cells.We propose that this difference occurs due to a loss of adhesion molecules presented at the apical membranes of the poorly-differentiated SK-Hep-1 cells,thereby reducing their adhesion to the surface.Our results provide new insight into the relationship between carcinoma cell differentiation grade and mobility.Further this experimental process may provide a simple and effective model for universal cell biology studies and applications in microsystems technology.展开更多
Transparent conductive films that are based on nanowire networks are essential to construct flexible,wearable,and even stretchable electronics.However,large-scale precise micropatterning,especially with regard to the ...Transparent conductive films that are based on nanowire networks are essential to construct flexible,wearable,and even stretchable electronics.However,large-scale precise micropatterning,especially with regard to the controllability of the organizing orientation of nanowires,is a critical challenge.Herein,we proposed a liquid film rupture self-assembly approach for manufacturing transparent conductive films with microstructure arrays based on a highly ordered nanowire network.The large-scale microstructure conductive films were fabricated through air-liquid interface self-assembly and liquid film rupture self-assembly.Six typical micropattern morphologies,including square,hexagon,circle,serpentine,etc.,were prepared to reveal the universal applicability of the proposed approach.The homogeneity and controllability of this approach were verified for multiple assemblies.With the assembly cycles increasing,the optical transmittance decreases slightly.In addition,theoretical model analysis is carried out,and the analytical formula of the speed of the film moving with the surface tension and the density of the liquid film is presented.Finally,the feasibility of this approach for piezoresistive strain sensors is verified.This fabrication approach demonstrated a cost-effective and efficient method for precisely arranging nanowires,which is useful in transparent and wearable applications.展开更多
Micropatterning is a sophisticated technique that precisely manipulates the spatial distribution of cell adhesion proteins on various substrates across multiple scales.This precise control over adhesive regions facili...Micropatterning is a sophisticated technique that precisely manipulates the spatial distribution of cell adhesion proteins on various substrates across multiple scales.This precise control over adhesive regions facilitates the manipulation of architectures and physical constraints for single or multiple cells.Furthermore,it allows for an indepth analysis of how chemical and physical properties influence cellular functionality.In this comprehensive review,we explore the current understanding of the impact of geometrical confinement on cellular functions across various dimensions,emphasizing the benefits of micropatterning in addressing fundamental biological queries.We advocate that utilizing directed self-organization via physical confinement and morphogen gradients on micropatterned surfaces represents an innovative approach to generating functional tissue and controlling morphogenesis in vitro.Integrating this technique with cutting-edge technologies,micropatterning presents a significant potential to bridge a crucial knowledge gap in understanding core biological processes.展开更多
Microbatteries(MBs)are crucial to power miniaturized devices for the Internet of Things.In the evolutionary journey of MBs,fabrication technology emerges as the cornerstone,guiding the intricacies of their configurati...Microbatteries(MBs)are crucial to power miniaturized devices for the Internet of Things.In the evolutionary journey of MBs,fabrication technology emerges as the cornerstone,guiding the intricacies of their configuration designs,ensuring precision,and facilitating scalability for mass production.Photolithography stands out as an ideal technology,leveraging its unparalleled resolution,exceptional design flexibility,and entrenched position within the mature semiconductor industry.However,comprehensive reviews on its application in MB development remain scarce.This review aims to bridge that gap by thoroughly assessing the recent status and promising prospects of photolithographic microfabrication for MBs.Firstly,we delve into the fundamental principles and step-by-step procedures of photolithography,offering a nuanced understanding of its operational mechanisms and the criteria for photoresist selection.Subsequently,we highlighted the specific roles of photolithography in the fabrication of MBs,including its utilization as a template for creating miniaturized micropatterns,a protective layer during the etching process,a mold for soft lithography,a constituent of MB active component,and a sacrificial layer in the construction of micro-Swiss-roll structure.Finally,the review concludes with a summary of the key challenges and future perspectives of MBs fabricated by photolithography,providing comprehensive insights and sparking research inspiration in this field.展开更多
Surface patterning is very useful in biomaterial studies, yet it is not easy to prepare a micropattern with cell-adhesion contrast that is stable in a wet environment. Recently, a platform technique of transfer photol...Surface patterning is very useful in biomaterial studies, yet it is not easy to prepare a micropattern with cell-adhesion contrast that is stable in a wet environment. Recently, a platform technique of transfer photolithography was invented to fabricate stable metal microarrays on the surface of a cell-adhesion resistant and mechanically biomimetic poly（ethylene glycol） hydrogel; the linker is the key chemical in such a transfer strategy. This article reports the design and synthesis of a hetero-bifunctional macromonomer linker with a thiol group at one end and an acryloyl group at the other end. The bifunctional linker was char- acterized by GPC and ~H NMR, and the average number of thiol groups in the bifunctional linker was detected by Ellman＇s reagent. The regent stability under wet conditions was also confirmed by the model reactants. The resultant micropatterned surfaces are meaningful for future studies of cell behaviors on mechanically biomimetic matrixes.展开更多
Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo.However,they have not been combined simultaneously ...Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo.However,they have not been combined simultaneously onto a biodegradable scaffold to demonstrate the synergistic role so far.In this study,a proof-of-concept study is performed to prepare micropatterns and peptide gradient on the inner wall of a poly(D,L-lactide-co-caprolactone)(PLCL)guidance conduit and its advantages in regeneration of peripheral nerve in vivo.After linear ridges/grooves of 20/40μm in width are created on the PLCL film,its surface is aminolyzed in a kinetically controlled manner to obtain the continuous gradient of amino groups,which are then transferred to CQAASIKVAV peptide density gradient via covalent coupling of glutaraldehyde.The Schwann cells are better aligned along with the stripes,and show a faster migration rate toward the region of higher peptide density.Implantation of the nerve guidance conduit made of the PLCL film having both the micropatterns and peptide gradient can significantly accelerate the regeneration of sciatic nerve in terms of rate,function recovery and microstructures,and reduction of fibrosis in muscle tissues.Moreover,this nerve conduit can also benefit the M2 polarization of macrophages and promote vascularization in vivo.展开更多
Immunoisolation is an important strategy to protect transplanted cells from rejection by the host immune system.Recently,microfabrication techniques have been used to create hydrogel membranes to encapsulate microtiss...Immunoisolation is an important strategy to protect transplanted cells from rejection by the host immune system.Recently,microfabrication techniques have been used to create hydrogel membranes to encapsulate microtissue in an arrayed organization.The method illustrates a new macroencapsulation paradigm that may allow transplantation of a large number of cells with microscale spatial control,while maintaining an encapsulation device that is easily maneuverable and remaining integrated following transplantation.This study aims to investigate the design principles that relate to the translational application of micropatterned encapsulation membranes,namely,the control over the transplantation density/quantity of arrayed microtissues and the fidelity of pre-formed microtissues to micropatterns.Agarose hydrogel membranes with microwell patterns were used as a model encapsulation system to exemplify these principles.Our results show that high-density micropatterns can be generated in hydrogel membranes,which can potentially maximize the percentage volume of cellular content and thereby the transplantation efficiency of the encapsulation device.Direct seeding of microtissues demonstrates that microwell structures can efficiently position and organize pre-formed microtissues,suggesting the capability of micropatterned devices for manipulation of cellular transplants at multicellular or tissue levels.Detailed theoretical analysis was performed to provide insights into the relationship between micropatterns and the transplantation capacity of membrane-based encapsulation.Our study lays the ground for developing new macroencapsulation systems with microscale cellular/tissue patterns for regenerative transplantation.展开更多
基金the National Natural Science Foundation of China(NSFC,Grant Nos.61975213,61475164,51901234,and 61205194)National Key R&D Program of China(Grant Nos.2017YFB1104300and 2016YFA0200500)+2 种基金International Partnership Program of Chinese Academy of Sciences(GJHZ2021130)Cooperative R&D Projects between Austria,FFG and China,CAS(GJHZ1720)supported by JSPS Bilateral Program Number JPJSBP120217203。
文摘Chitosan(CS)-based nanocomposites have been studied in various fields,requiring a more facile and efficient technique to fabricate nanoparticles with customized structures.In this study,Ag@methacrylamide CS/poly(ethylene glycol)diacrylate(Ag@MP)micropatterns are successfully fabricated by femtosecond laser maskless optical projection lithography(Fs-MOPL)for the first time.The formation mechanism of core-shell nanomaterial is demonstrated by the local surface plasmon resonances and the nucleation and growth theory.Amino and hydroxyl groups greatly affect the number of Ag@MP nanocomposites,which is further verified by replacing MCS with methacrylated bovine serum albumin and hyaluronic acid methacryloyl,respectively.Besides,the performance of the surface-enhanced Raman scattering,cytotoxicity,cell proliferation,and antibacterial was investigated on Ag@MP micropatterns.Therefore,the proposed protocol to prepare hydrogel core-shell micropattern by the home-built Fs-MOPL technique is prospective for potential applications in the biomedical and biotechnological fields,such as biosensors,cell imaging,and antimicrobial.
基金The National Science Foundation(NSF)through Grants ECCS-2111056 and CMMI-1846863.
文摘Over the course of millions of years,nature has evolved to ensure survival and presents us with a myriad of functional surfaces and structures that can boast high efficiency,multifunctionality,and sustainability.What makes these surfaces particularly practical and effective is the intricate micropatterning that enables selective interactions with microstructures.Most of these structures have been realized in the laboratory environment using numerous fabrication techniques by tailoring specific surface properties.Of the available manufacturing methods,additive manufacturing(AM)has created opportunities for fabricating these structures as the complex architectures of the naturally occurring microstructures far exceed the traditional ways.This paper presents a concise overview of the fundamentals of such patterned microstructured surfaces,their fabrication techniques,and diverse applications.A comprehensive evaluation of micro fabrication methods is conducted,delving into their respective strengths and limitations.Greater emphasis is placed on AM processes like inkjet printing and micro digital light projection printing due to the intrinsic advantages of these processes to additively fabricate high resolution structures with high fidelity and precision.The paper explores the various advancements in these processes in relation to their use in microfabrication and also presents the recent trends in applications like the fabrication of microlens arrays,microneedles,and tissue scaffolds.
基金supported by the National Natural Science Foundation of China(Nos.12174208,32227802)National Key Research and Development Program of China(No.2022YFC3400600)+3 种基金Guangdong Major Project of Basic and Applied Basic Research(No.2020B0301030009)China Postdoctoral Science Foundation(No.2020 M680032)Fundamental Research Funds for the Central Universities(Nos.2122021337,2122021405)the 111 Project(No.B23045).
文摘Cells are highly sensitive to their geometrical and mechanical microenvironment that directly regulate cell shape,cytoskeleton and organelle,as well as the nucleus morphology and genetic expression.The emerging two-dimensional micropatterning techniques offer powerful tools to construct controllable and well-organized microenvironment for single-cell level investigations with qualitative analysis,cellular standardization,and in vivo environment mimicking.Here,we provide an overview of the basic principle and characteristics of the two most widely-used micropatterning techniques,including photolithographic micropatterning and soft lithography micropatterning.Moreover,we summarize the application of micropatterning technique in controlling cytoskeleton,cell migration,nucleus and gene expression,as well as intercellular communication.
文摘Nerve conduits have been a viable alternative to the ‘gold standard’ autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion （DRG） cells on poly（lactic-co-glycolic acid） （PLGA） films has not been previously conducted. Photolithography and micro-molding were used to define various combinations of ridge/groove dimensions on PLGA films. The DRG cells obtained from chicken embryos were cultured on micropatterned PLGA films for cell orientation and migration evaluation.Biodegradation of the films occurred during the test period, however, this did not cause deformation or distortion of the micropatterns. Results from the DRG cell orientation test suggest that when the ridge/groove ratio equals 1 （ridge/groove width parameters are equal, i.e., 10 μm/10 μm （even））, the degree of alignment depends on the size of the ridges and grooves, when the ratio is smaller than 1 （groove controlled） the alignment increases as the ridge size decreases, and when the ratio is larger than 1 （ridge controlled）, the alignment is reduced as the width of the grooves decreases. The migration rate and neurite extension of DRG neurons were greatest on 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films. Based on the data, the 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films are the optimized ridge/groove surface patterns for the construction of nerve repair devices.
文摘After decades of research,peripheral nerve injury and repair still frequently results in paralysis,chronic pain and neuropathies leading to severe disability in patients.Current clinically available nerve conduits only provide crude guidance of regenerating axons across nerve gap without additional functionality.FK506（Tacrolimus）,an FDA approved immunosuppressant,has been shown to enhance peripheral nerve regeneration but carries harsh side-effects when delivered systemically.The objective of this study was to develop and evaluate a bioresorbable drug delivery system capable of local extended delivery of FK506 that also provides topological guidance cues to guide axon growth via microgrooves.Photolithography was used to create micropatterned poly（lactide-co-glycolic acid）（PLGA） films embedded with FK506.Non-patterned,10/10 μm（ridge/groove width）,and 30/30 μm patterned films loaded with 0,1,and 3 μg/cm2 FK506 were manufactured and characterized.In vitro FK506 rate of release testing indicated that the films are capable of an extended（at least 56 days）,controlled,and scalable release of FK506.Neurite extension bioactivity assay indicated that FK506 released from the films（concentration of samples tested ranged between 8.46–19.7 ng/m L） maintained its neural bioactivity and promoted neurite extension similar to control FK506 dosages（10 ng/m L FK506）.The multi-functional FK506 embedded,micropatterned poly（lactide-co-glycolic acid） films developed in this study have potential to be used in the construction of peripheral nerve repair devices.
基金This work was supported by the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030009)the National Key Research and Development Program of China(2022YFC3400600)National Natural Science Foundation of China(12174208,32227802,11874231,31801134 and 31870843)+2 种基金Tianjin Natural Science Foundation(20JCYBJC01010)China Postdoctoral Science Foundation(2020M680032)Fundamental Research Funds for the Central Universities(2122021337 and 2122021405).
文摘Actin cytoskeleton plays crucial roles in various cellular functions.Extracellular matrix(ECM)can modulate cell morphology by remodeling the internal cytoskeleton.To define how geometry of ECM regulates the organization of actin cytoskeleton,we plated individual NIH 3T3 cells on micropatterned substrates with distinct shapes and sizes.It was found that the stress fibers could form along the nonadhesive edges of T-shaped pattern,but were absent from the opening edge of V-shaped pattern,indicating that the organization of actin cytoskeleton was dependent on the mechanical environment.Furthermore,a secondary actin ring was observed on 50μm circular pattern while did not appear on 30μm and 40μm pattern,showing a size-dependent organization of actin cytoskeleton.Finally,osteoblasts,MDCK and A549 cells exhibited distinct organization of actin cytoskeleton on T-shaped pattern,suggesting a cell-type specificity in arrangement of actin cytoskeleton.Together,our findings brought novel insight into the organization of actin cytoskeleton on micropatterned environments.
基金Project(LY19A040001)supported by the Natural Science Foundation of Zhejiang Province,ChinaProjects(12147219,12035006)supported by the National Natural Science Foundation of China+1 种基金Project(531107050927)supported by the Fundamental Research Funds for the Central Universities,ChinaProject(JY-Q/008/2016)supported by the Hunan University for the Yuelu Young Scholars,China。
文摘Poly(ε-caprolactone)(PCL)holds unique bioresorbability and competent biomechanical properties for tissueengineering application.However,PCL is hydrophobic intrinsically and poor in cell-biomaterial interaction.In this study,we prepared a composite based on PCL and bioactive tantalum(Ta)to understand the effects of direct laser micropatterning on composite surface properties.The PCL/Ta composite after preparation was surface-patterned by femtosecond laser and characterized with surface morphology,crystal structure,chemical composition,wettability and cellular response of fibroblast.It was found that laser micropatterning enlarged the difference of wetting properties(~15°)on PCL and PCL/Ta surfaces.The wetting changes was dependent on both material composition and lasermachined geometry.The blending of Ta enhanced surface wettability with prolonged contact time on the laser-machined line and rectangle microarrays.In vitro culture results showed beneficial effects of laser micropatterning on cell morphology of the fibroblasts.On the PCL/Ta surfaces with line and rectangle microarrays,the cells were more likely to bridge the sidewalls of the microgrooves,showing adaptive 3D morphologies to the micro/nano topographies on the sidewalls.These findings are envisaged to facilitate surface design and micropattern optimization for favorable tuning the cell response to biomedical PCL/Ta composites.
基金Supports from the National Natural Science Foundation of China(11602027)the National Science Foundation for Post-doctoral Scientists of China(2016M600969)
文摘Flower petals have not only diverse macroscopic morphologies but are rich in microscopic surface patterns, which are crucial to their biological functions. Both experimental measurements and theoretical analysis are conducted to reveal the physical mechanisms underlying the formation of minute wrinkles on flower petals. Three representative flowers, daisy, kalanchoe blossfeldiana, and Eustoma grandiflorurn, are investigated as examples. A surface wrinkling model, incorporating the measured mechanical properties and growth ratio, is used to elucidate the difference in their surface morphologies. The mismatch between the anisotropic epidermal cell growth and the isotropic secretion of surficial wax is found to dictate the surface patterns.
基金the National Key R&D Program of China(Grant No.2018YFA0209200)the National Natural Science Foundation of China(Grant No.21574049)。
文摘Here, we demonstrate an in-situ growth of micropatterned silver nanospheres(Ag NS) array on transparent polyimide(PI), namely PI-Ag substrate, applied as a flexible platform for metal-enhanced fluorescence(MEF). The scheme proposed here can easily control the grid formation of Ag NSs and the particle size inside, thus achieving patterned fluorescence imaging and MEF efficiency optimization. Meanwhile, the magnitude of enhanced intensity, relying on the distance between Ag NSs and emissive molecules, was systematically investigated by exploring diverse polyethyleneimine(PEI) spacer thickness. Consequently,an optimal enhancement factor of 7.9 and a pattern of grid fluorescence imaging was obtained with an insertion of 10 nm PEI on the PI-Ag(25 nm) platform. Moreover, owing to robust adhesion between Ag NSs and PI film by in-situ growth, this flexible PI-Ag MEF platform maintained a stable MEF efficiency even after taking mechanical bending for 1000 cycles. This new surface-confined micropatterned Ag NSs PI film provides a promising candidate in design flexible MEF platforms for future analytical and clinical sensing applications.
基金supported by the National Natural Science Foundation of China(T2288101,31971266,82272152)Guangdong Basic and Applied Basic Research Foundation(2022A1515011925)+2 种基金National Key R&D Program of China(2021YFC2400700)Science and Technology Innovation Program of Guangdong Province Medical Products Administration(2022ZDZ11)Applied Basic Research Program of Guangzhou city of China(202201010040).
文摘Mitochondrial network architecture,which is closely related to mitochondrial function,is mechanically sensitive and regulated by multiple stimuli.However,the effects of microtopographic cues on mitochondria remain poorly defined.Herein,polycaprolactone(PCL)surfaces were used as models to investigate how micropatterns regulate mitochondrial network architecture and function in rat adipose-derived stem cells(rASCs).It was found that large pit(LP)-induced rASCs to form larger and more complex mitochondrial networks.Consistently,the expression of key genes related to mitochondrial dynamics revealed that mitochondrial fusion(MFN1 and MFN2)and midzone fission(DRP1 and MFF)were increased in rASCs on LP.In contrast,the middle pit(MP)-enhanced mitochondrial biogenesis,as evidenced by the larger mitochondrial area and higher expression of PGC-1.Both LP and MP promoted ATP production in rASCs.It is likely that LP increased ATP levels through modulating mitochondrial network architecture while MP stimulated mitochondria biogenesis to do so.Our study clarified the regulation of micropatterned surfaces on mitochondria,highlighting the potential of LP and MP as a simple platform to stimulate mitochondria and the subsequent cellular function of MSCs.
基金the National Science Council(NSC 99-2113-M-110-005 and 99-2738-M-110-001)of Taiwanthe National Sun Yat-sen University Center for Nanoscience and Nanotechnology,and the Kaohsiung Veterans General Hospital(VGHNSU100-001)for financial support of this work.
文摘Cell migration influences many normal and pathological processes and is one of key issues addressed in cancer research studies.In this report,a plasma patterned polydimethylsiloxane(PDMS)substrate was used to selectively position hepatocarcinoma cells in order to characterize their migration behavior.We observed that cell mobility was directly related to the differentiation stage of the cells,with poorly-differentiated(SK-Hep-1)cells exhibiting higher mobility that well-differentiated(Hep-G2)cells.We propose that this difference occurs due to a loss of adhesion molecules presented at the apical membranes of the poorly-differentiated SK-Hep-1 cells,thereby reducing their adhesion to the surface.Our results provide new insight into the relationship between carcinoma cell differentiation grade and mobility.Further this experimental process may provide a simple and effective model for universal cell biology studies and applications in microsystems technology.
基金supported by the National Natural Science Foundation of China(Nos.62074029,61905035,61971108,62004029,51905554)the National Key Research and Development Program of China(No.2022YFB3206100)+3 种基金the Key R&D Program of Sichuan Province(Nos.2022JDTD0020,2020ZHCG0038)the Sichuan Science and Technology Program(Nos.2020JDJQ0036,2019YJ0198,2020YJ0015)the Natural Science Foundation of Sichuan(No.2022NSFSC1941)the Fundamental Research Funds for the Central Universities(No.ZYGX2019Z002).
文摘Transparent conductive films that are based on nanowire networks are essential to construct flexible,wearable,and even stretchable electronics.However,large-scale precise micropatterning,especially with regard to the controllability of the organizing orientation of nanowires,is a critical challenge.Herein,we proposed a liquid film rupture self-assembly approach for manufacturing transparent conductive films with microstructure arrays based on a highly ordered nanowire network.The large-scale microstructure conductive films were fabricated through air-liquid interface self-assembly and liquid film rupture self-assembly.Six typical micropattern morphologies,including square,hexagon,circle,serpentine,etc.,were prepared to reveal the universal applicability of the proposed approach.The homogeneity and controllability of this approach were verified for multiple assemblies.With the assembly cycles increasing,the optical transmittance decreases slightly.In addition,theoretical model analysis is carried out,and the analytical formula of the speed of the film moving with the surface tension and the density of the liquid film is presented.Finally,the feasibility of this approach for piezoresistive strain sensors is verified.This fabrication approach demonstrated a cost-effective and efficient method for precisely arranging nanowires,which is useful in transparent and wearable applications.
基金supported by start-up funding(grant OJQD2022015)from Oujiang Laboratorythe National Natural Science Foundation of China(grant 82301873).
文摘Micropatterning is a sophisticated technique that precisely manipulates the spatial distribution of cell adhesion proteins on various substrates across multiple scales.This precise control over adhesive regions facilitates the manipulation of architectures and physical constraints for single or multiple cells.Furthermore,it allows for an indepth analysis of how chemical and physical properties influence cellular functionality.In this comprehensive review,we explore the current understanding of the impact of geometrical confinement on cellular functions across various dimensions,emphasizing the benefits of micropatterning in addressing fundamental biological queries.We advocate that utilizing directed self-organization via physical confinement and morphogen gradients on micropatterned surfaces represents an innovative approach to generating functional tissue and controlling morphogenesis in vitro.Integrating this technique with cutting-edge technologies,micropatterning presents a significant potential to bridge a crucial knowledge gap in understanding core biological processes.
基金supported by the National Natural Science Foundation of China(22125903,22439003,22209175)the National Key R&D Program of China(Grant 2022YFA1504100,2023YFB4005204)+1 种基金the Energy Revolution S&T Program of Yulin Innovation Institute of Clean Energy(Grant E412010508)the State Key Laboratory of Catalysis(No:2024SKL-A-001)。
文摘Microbatteries(MBs)are crucial to power miniaturized devices for the Internet of Things.In the evolutionary journey of MBs,fabrication technology emerges as the cornerstone,guiding the intricacies of their configuration designs,ensuring precision,and facilitating scalability for mass production.Photolithography stands out as an ideal technology,leveraging its unparalleled resolution,exceptional design flexibility,and entrenched position within the mature semiconductor industry.However,comprehensive reviews on its application in MB development remain scarce.This review aims to bridge that gap by thoroughly assessing the recent status and promising prospects of photolithographic microfabrication for MBs.Firstly,we delve into the fundamental principles and step-by-step procedures of photolithography,offering a nuanced understanding of its operational mechanisms and the criteria for photoresist selection.Subsequently,we highlighted the specific roles of photolithography in the fabrication of MBs,including its utilization as a template for creating miniaturized micropatterns,a protective layer during the etching process,a mold for soft lithography,a constituent of MB active component,and a sacrificial layer in the construction of micro-Swiss-roll structure.Finally,the review concludes with a summary of the key challenges and future perspectives of MBs fabricated by photolithography,providing comprehensive insights and sparking research inspiration in this field.
基金supported by the National Natural Science Foundation of China(21034002,91127028,51273046)the Ministry of Science and Technology of China(2011CB606203)the Science and Technology Development Foundation of Shanghai(13XD1401000)
文摘Surface patterning is very useful in biomaterial studies, yet it is not easy to prepare a micropattern with cell-adhesion contrast that is stable in a wet environment. Recently, a platform technique of transfer photolithography was invented to fabricate stable metal microarrays on the surface of a cell-adhesion resistant and mechanically biomimetic poly（ethylene glycol） hydrogel; the linker is the key chemical in such a transfer strategy. This article reports the design and synthesis of a hetero-bifunctional macromonomer linker with a thiol group at one end and an acryloyl group at the other end. The bifunctional linker was char- acterized by GPC and ~H NMR, and the average number of thiol groups in the bifunctional linker was detected by Ellman＇s reagent. The regent stability under wet conditions was also confirmed by the model reactants. The resultant micropatterned surfaces are meaningful for future studies of cell behaviors on mechanically biomimetic matrixes.
基金This study is financially supported by the National Key Research and Development Program of China(2016YFC1100403)the National Natural Science Foundation of China(21434006,51873188)and the Fundamental Research Funds for the Central Universities of China(2020XZZX004-01).
文摘Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo.However,they have not been combined simultaneously onto a biodegradable scaffold to demonstrate the synergistic role so far.In this study,a proof-of-concept study is performed to prepare micropatterns and peptide gradient on the inner wall of a poly(D,L-lactide-co-caprolactone)(PLCL)guidance conduit and its advantages in regeneration of peripheral nerve in vivo.After linear ridges/grooves of 20/40μm in width are created on the PLCL film,its surface is aminolyzed in a kinetically controlled manner to obtain the continuous gradient of amino groups,which are then transferred to CQAASIKVAV peptide density gradient via covalent coupling of glutaraldehyde.The Schwann cells are better aligned along with the stripes,and show a faster migration rate toward the region of higher peptide density.Implantation of the nerve guidance conduit made of the PLCL film having both the micropatterns and peptide gradient can significantly accelerate the regeneration of sciatic nerve in terms of rate,function recovery and microstructures,and reduction of fibrosis in muscle tissues.Moreover,this nerve conduit can also benefit the M2 polarization of macrophages and promote vascularization in vivo.
基金supported by the Key New Drug Creation and Manufacturing Program(2011ZX09102-010-03)the National Natural Science Foundation of China(31170933)
文摘Immunoisolation is an important strategy to protect transplanted cells from rejection by the host immune system.Recently,microfabrication techniques have been used to create hydrogel membranes to encapsulate microtissue in an arrayed organization.The method illustrates a new macroencapsulation paradigm that may allow transplantation of a large number of cells with microscale spatial control,while maintaining an encapsulation device that is easily maneuverable and remaining integrated following transplantation.This study aims to investigate the design principles that relate to the translational application of micropatterned encapsulation membranes,namely,the control over the transplantation density/quantity of arrayed microtissues and the fidelity of pre-formed microtissues to micropatterns.Agarose hydrogel membranes with microwell patterns were used as a model encapsulation system to exemplify these principles.Our results show that high-density micropatterns can be generated in hydrogel membranes,which can potentially maximize the percentage volume of cellular content and thereby the transplantation efficiency of the encapsulation device.Direct seeding of microtissues demonstrates that microwell structures can efficiently position and organize pre-formed microtissues,suggesting the capability of micropatterned devices for manipulation of cellular transplants at multicellular or tissue levels.Detailed theoretical analysis was performed to provide insights into the relationship between micropatterns and the transplantation capacity of membrane-based encapsulation.Our study lays the ground for developing new macroencapsulation systems with microscale cellular/tissue patterns for regenerative transplantation.
