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Design and aligner-assisted fast fabrication of a microfluidic platform for quasi-3D cell studies on an elastic polymer

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Bioactive materials 2022年第9期7卷 288-304页

作者： Yingning He Yue Yu Yuqian Yang Yexin Gu Tianjiao Mao Yang Shen Qiong Liu Ruili Liu Jiandong Ding State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceFudan UniversityShanghai200438China Translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai200434China

While most studies of mechanical stimulation of cells are focused on two-dimensional(2D)and three-dimensional(3D)systems,it is rare to study the effects of cyclic stretching on cells under a quasi-3D microenvironment as a linkage between 2D and 3D.Herein,we report a new method to prepare an elastic membrane with topographic microstructures and integrate the membrane into a microfluidic chip.The fabrication difficulty lay not only in the preparation of microstructures but also in the alignment and bonding of the patterned membrane to other layers.To resolve the problem,we designed and assembled a fast aligner that is cost-effective and convenient to operate.To enable quasi-3D microenvironment of cells,we fabricated polydimethylsiloxane(PDMS)microwell arrays(formed by micropillars of a few microns in diameter)with the microwell diameters close to the cell sizes.An appropriate plasma treatment was found to afford a coating-free approach to enable cell adhesion on PDMS.We examined three types of cells in 2D,quasi-3D,and 3D microenvironments;the cell adhesion results showed that quasi-3D cells behaved between 2D and 3D cells.We also constructed transgenic human mesenchymal stem cells(hMSCs);under cyclic stretching,the visualizable live hMSCs in microwells were found to orientate differently from in a 3D Matrigel matrix and migrate differently from on a 2D flat plate.This study not only provides valuable tools for microfabrication of a microfluidic device for cell studies,but also inspires further studies of the topological effects of biomaterials on cells.

关键词： Microfluidic chip Biomaterials cell-material interaction Polymer cell stretching

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The influence of nanotopography on cell behaviour through interactions with the extracellular matrix-A review

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Bioactive materials 2022年第9期7卷 145-159页

作者： Jiajun Luo Matthew Walker Yinbo Xiao Hannah Donnelly Matthew J.Dalby Manuel Salmeron-Sanchez Centre for the cellular Microenvironment University of GlasgowGlasgowG128LTUK

Nanotopography presents an effective physical approach for biomaterial cell manipulation mediated through material-extracellular matrix interactions.The extracellular matrix that exists in the cellular microenvironment is crucial for guiding cell behaviours,such as determination of integrin ligation and interaction with growth factors.These interactions with the extracellular matrix regulate downstream mechanotransductive pathways,such as rearrangements in the cytoskeleton and activation of signal cascades.Protein adsorption onto nanotopography strongly influences the conformation and distribution density of extracellular matrix and,therefore,subsequent cell responses.In this review,we first discuss the interactive mechanisms of protein physical adsorption on nanotopography.Secondly,we summarise advances in creating nanotopographical features to instruct desired cell behaviours.Lastly,we focus on the cellular mechanotransductive pathways initiated by nanotopography.This review provides an overview of the current state-of-the-art designs of nanotopography aiming to provide better biomedical materials for the future.

关键词： Nanotopography cell-material interaction Protein adsorption Biomaterials

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3D additive-manufactured nanocomposite magnetic scaffolds: Effect of the application mode of a time-dependent magnetic field on hMSCs behavior

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Bioactive materials 2017年第3期2卷 138-145页

作者： Ugo D'Amora Teresa Russo Antonio Gloria Virginia Rivieccio Vincenzo D'Anto Giacomo Negri Luigi Ambrosio Roberto De Santis Institute of Polymers Composites and BiomaterialsNational Research CouncilNaplesItaly Villa Betania Evangelical Hospital NaplesItaly Department of Neuroscience Reproductive Sciences and Oral SciencesUniversity of Naples Federico IINaplesItaly Unit of Dentistry Bambino GesùChildren's HospitalIRCCSRomeItaly

Over the past few years,the influence of static or dynamic magnetic fields on biological systems has become a topic of considerable interest.Magnetism has recently been implicated to play significant roles in the regulation of cell responses and,for this reason,it is revolutionizing many aspects of healthcare,also suggesting new opportunities in tissue engineering.The aim of the present study was to analyze the effect of the application mode of a time-dependent magnetic field on the behavior of human mesenchymal stem cells(hMSCs)seeded on 3D additivemanufactured poly(3-caprolactone)/iron-doped hydroxyapatite(PCL/FeHA)nanocomposite scaffolds.

关键词： Additive manufacturing Scaffold Magnetic field cell-material interaction

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Micro and Nanofabrication methods to control cell-substrate interactions and cell behavior: A review from the tissue engineering perspective

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Bioactive materials 2018年第3期3卷 355-369页

作者： Menekse Ermis Ezgi Antmen Vasif Hasirci BIOMATEN Middle East Technical University(METU)Center of Excellence in Biomaterials and Tissue EngineeringAnkaraTurkey METU Department of Biomedical EngineeringAnkaraTurkey METU Department of BiotechnologyAnkaraTurkey METU Department of Biological SciencesAnkaraTurkey

cell-substrate interactions play a crucial role in the design of better biomaterials and integration ofimplants with the tissues. Adhesion is the binding process of the cells to the substrate through interactionsbetween the surface molecules of the cell membrane and the substrate. There are severalfactors that affect cell adhesion including substrate surface chemistry, topography, and stiffness. Thesefactors physically and chemically guide and influence the adhesion strength, spreading, shape and fate ofthe cell. Recently, technological advances enabled us to precisely engineer the geometry and chemistry ofsubstrate surfaces enabling the control of the interaction cells with the substrate. Some of the mostcommonly used surface engineering methods for eliciting the desired cellular responses on biomaterialsare photolithography, electron beam lithography, microcontact printing, and microfluidics. Thesemethods allow production of nano- and micron level substrate features that can control cell adhesion,migration, differentiation, shape of the cells and the nuclei as well as measurement of the forces involvedin such activities. This review aims to summarize the current techniques and associate these techniqueswith cellular responses in order to emphasize the effect of chemistry, dimensions, density and design ofsurface patterns on cell-substrate interactions. We conclude with future projections in the field of cellsubstrateinteractions in the hope of providing an outlook for the future studies.

关键词： Microfabrication Micropattern cell-material interaction Differentiation cell adhesion

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Left-Right Symmetry or Asymmetry of cells on Stripe-Like Micropatterned material Surfaces

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Chinese Journal of Chemistry 2018年第7期36卷 605-611页

作者： Yiwen Hu Xiang Yao Qiong Liu Yi Wang Ruili Liu Shuquan Cui Jiandong Ding State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular Science Fudan University Shanghai 200438 China

material surfaces can induce cell responses such as contact guidance, yet little attention has been paid to further cell orientation. Herein, we report an interesting phenomenon of cell orientation beyond the classic contact guidance on a stripe-like micropattern with cell-adhesive arginineglycine-aspartate （RGD） peptides on a nonfouling background decorated by poly（ethylene glycol）（PEG）. Such a micropattern with cell adhesion contrast led to significant contact guidance after cell seeding. What is more, the localized and elongated cells were found to be further orientated out of the adhesive stripes, and even an anticlockwise rotation was observed for rat mesenchymal stem cells （rMSCs）. The left-right asymmetry of rMSCs stood only in statistics, for we observed all cases including clockwise orientation, anticlockwise orientation or just keeping the orientation of previous contact guidance. We further found that human foreskin fibroblasts （HFFs） preferred a clockwise rotation, while human mesenchymal stem cells （hMSCs） and human umbilical vascular endothelial cells （HUVECs） exhibited no significant preference to either direction, which indicated that the left-right symmetry or asymmetry was cell-type dependent. The present report has partially confirmed the cell chirality and revealed its complexity, calling for further careful and comprehensive investigation of the challenging topic of cell chirality on material surfaces.

关键词： polymers surface chemistry biomaterials cell-material interaction chirality

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Biomaterial nanotopography-mediated cell responses:experiment and modeling

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International Journal of Smart and Nano materials 2014年第4期5卷 227-256页

作者： Lei Yang Haipei Liu Yuan Lin Institute of Orthopaedics and Department of Orthopaedic Surgery The First Affiliated HospitalSoochow UniversitySuzhou 215006PR China Department of Mechanical Engineering The University of Hong KongPokfulam RoadHong KongPR China

The rapid development of fabrication and processing technologies in the past two decades has enabled researchers to introduce nanoscale features into materials which,interestingly,have been shown to greatly regulate the behavior and fate of biological cells.In particular,important cell responses(such as adhesion,proliferation,differentiation,migration,and filopodial growth)have all been correlated with material nanotopography.Given its great potential,intensive efforts have been made,both experimentally and theoretically,to understand why and how cells respond to nanoscale surface features,and this article reviews recent progress in this field.Specifically,a brief overview on the fabrication and modification techniques to create nanotopography on different materials is given first.After that,a summary of important experimental findings on the mediation of nanoscale surface topography on the behavior of various cells,as well as the underlying mechanism,is provided.Finally,both classical and recently developed approaches for modeling nanotopographymediated cell adhesion and filopodial growth are reviewed.

关键词： biomaterials topography cell-material interaction experiment modeling

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