Design of capillary microfluidics for spinning cell-laden microfibers

This protocol describes the design of capillary microfluidics for spinning bioactive (cell-laden) microfibers for three-dimensional (3D) cell culture and tissue-engineering applications. We describe the assembly of three types of microfluidic systems: (i) simple injection capillary microfluidics for the spinning of uniform microfibers; (ii) hierarchical injection capillary microfluidics for the spinning of core–shell or spindle-knot structured microfibers; and (iii) multi-barrel injection capillary microfluidics for the spinning of microfibers with multiple components. The diverse morphologies of these bioactive microfibers can be further assembled into higher-order structures that are similar to the hierarchical structures in tissues. Thus, by using different types of capillary microfluidic devices, diverse styles of microfibers with different bioactive encapsulation can be generated. These bioactive microfibers have potential applications in 3D cell culture, the mimicking of vascular structures, the creation of synthetic tissues, and so on. The whole protocol for device fabrication and microfiber spinning takes ~1 d.This protocol describes how to produce cell-laden microfibers using capillary microfluidic devices. The devices enable spinning of increasingly complex microfibers, which can function as building blocks for 3D cell culture and tissue engineering.

[1]  S. Quake,et al.  Monolithic microfabricated valves and pumps by multilayer soft lithography. , 2000, Science.

[2]  Yuanjin Zhao,et al.  Microfluidic generation of Buddha beads-like microcarriers for cell culture , 2017, Science China Materials.

[3]  A. Khademhosseini,et al.  Cell-laden microengineered gelatin methacrylate hydrogels. , 2010, Biomaterials.

[4]  K. Ren,et al.  Materials for microfluidic chip fabrication. , 2013, Accounts of chemical research.

[5]  S. Heilshorn,et al.  Adaptable Hydrogel Networks with Reversible Linkages for Tissue Engineering , 2015, Advanced materials.

[6]  A. Khademhosseini,et al.  Microfluidic fabrication of microengineered hydrogels and their application in tissue engineering. , 2012, Lab on a chip.

[7]  Chee Meng Benjamin Ho,et al.  3D printed microfluidics for biological applications. , 2015, Lab on a chip.

[8]  H. Stone,et al.  Dripping and jetting in microfluidic multiphase flows applied to particle and fibre synthesis , 2013, Journal of physics D: Applied physics.

[9]  Shuhong Yu,et al.  Spraying functional fibres by electrospinning , 2016 .

[10]  Hang Lu,et al.  Microfluidic‐Based Generation of Size‐Controlled, Biofunctionalized Synthetic Polymer Microgels for Cell Encapsulation , 2014, Advanced materials.

[11]  S. Takeuchi,et al.  Three-dimensional cell culture based on microfluidic techniques to mimic living tissues. , 2013, Biomaterials science.

[12]  David A Weitz,et al.  One-step emulsification of multiple concentric shells with capillary microfluidic devices. , 2011, Angewandte Chemie.

[13]  Yuanjin Zhao,et al.  Emerging Droplet Microfluidics. , 2017, Chemical reviews.

[14]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[15]  Yang Song,et al.  All-aqueous multiphase microfluidics. , 2013, Biomicrofluidics.

[16]  Tze Chiun Lim,et al.  Patterned prevascularised tissue constructs by assembly of polyelectrolyte hydrogel fibres , 2013, Nature Communications.

[17]  M. Gijs,et al.  Exploring living multicellular organisms, organs, and tissues using microfluidic systems. , 2013, Chemical reviews.

[18]  J. Vacanti,et al.  Tissue engineering. , 1993, Science.

[19]  Sindy K. Y. Tang,et al.  Cofabrication: a strategy for building multicomponent microsystems. , 2010, Accounts of chemical research.

[20]  Zhongze Gu,et al.  Controlled Fabrication of Bioactive Microfibers for Creating Tissue Constructs Using Microfluidic Techniques. , 2016, ACS applied materials & interfaces.

[21]  P. Russell Photonic Crystal Fibers , 2003, Science.

[22]  Pingan Zhu,et al.  Large-scale water collection of bioinspired cavity-microfibers , 2017, Nature Communications.

[23]  Kenneth M. Yamada,et al.  Modeling Tissue Morphogenesis and Cancer in 3D , 2007, Cell.

[24]  Yongping Chen,et al.  Bioinspired Multicompartmental Microfibers from Microfluidics , 2014, Advanced materials.

[25]  Ying Liu,et al.  Engineering of bio-hybrid materials by electrospinning polymer-microbe fibers , 2009, Proceedings of the National Academy of Sciences.

[26]  Brian Derby,et al.  Printing and Prototyping of Tissues and Scaffolds , 2012, Science.

[27]  A. Woolley,et al.  Advances in microfluidic materials, functions, integration, and applications. , 2013, Chemical reviews.

[28]  Michael A Daniele,et al.  Microfluidic Strategies for Design and Assembly of Microfibers and Nanofibers with Tissue Engineering and Regenerative Medicine Applications , 2015, Advanced healthcare materials.

[29]  Wei Zhang,et al.  A Strategy for Depositing Different Types of Cells in Three Dimensions to Mimic Tubular Structures in Tissues , 2012, Advanced materials.

[30]  J. Qin,et al.  Simple Spinning of Heterogeneous Hollow Microfibers on Chip , 2016, Advanced materials.

[31]  Molly M Stevens,et al.  Synthetic polymer scaffolds for tissue engineering. , 2009, Chemical Society reviews.

[32]  Su-Jung Shin,et al.  "On the fly" continuous generation of alginate fibers using a microfluidic device. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[33]  Ali Khademhosseini,et al.  Textile Technologies and Tissue Engineering: A Path Toward Organ Weaving , 2016, Advanced healthcare materials.

[34]  S. Shoji,et al.  Microfluidic Stamping on Sheath Flow. , 2016, Small.

[35]  P. Abgrall,et al.  Lab-on-chip technologies: making a microfluidic network and coupling it into a complete microsystem—a review , 2007 .

[36]  Jin Zhai,et al.  Directional water collection on wetted spider silk , 2010, Nature.

[37]  Z. Kang,et al.  Tip-multi-breaking in Capillary Microfluidic Devices , 2015, Scientific Reports.

[38]  Ali Khademhosseini,et al.  Digitally tunable physicochemical coding of material composition and topography in continuous microfibres. , 2011, Nature materials.

[39]  Jackie Y Ying,et al.  Hydrodynamic spinning of hydrogel fibers. , 2010, Biomaterials.

[40]  L. Daniel Söderberg,et al.  Hydrodynamic alignment and assembly of nanofibrils resulting in strong cellulose filaments , 2014, Nature Communications.

[41]  L. Chu,et al.  A novel synthetic microfiber with controllable size for cell encapsulation and culture. , 2016, Journal of materials chemistry. B.

[42]  Yuanjin Zhao,et al.  Microfluidic Lithography of Bioinspired Helical Micromotors. , 2017, Angewandte Chemie.

[43]  D. Beebe,et al.  Controlled microfluidic interfaces , 2005, Nature.

[44]  G. Luo,et al.  Bioinspired Microfibers with Embedded Perfusable Helical Channels , 2017, Advanced materials.

[45]  D. Ingber,et al.  From 3D cell culture to organs-on-chips. , 2011, Trends in cell biology.

[46]  Hui Wu,et al.  Direct Blow-Spinning of Nanofibers on a Window Screen for Highly Efficient PM2.5 Removal. , 2017, Nano letters.

[47]  Zhongze Gu,et al.  Bioinspired Helical Microfibers from Microfluidics , 2017, Advanced materials.

[48]  Guang Yang,et al.  Biomimetic nanofibers can construct effective tissue-engineered intervertebral discs for therapeutic implantation. , 2017, Nanoscale.

[49]  Sang-Hoon Lee,et al.  Electrospinning versus microfluidic spinning of functional fibers for biomedical applications. , 2017, Biomaterials.

[50]  Ali Khademhosseini,et al.  Fiber-assisted molding (FAM) of surfaces with tunable curvature to guide cell alignment and complex tissue architecture. , 2014, Small.

[51]  Zhongze Gu,et al.  Organ-on-a-Chip Systems: Microengineering to Biomimic Living Systems. , 2016, Small.

[52]  Hongkai Wu,et al.  Recent Developments in Microfluidics for Cell Studies , 2014, Advanced materials.

[53]  Sang-Hoon Lee,et al.  Microfluidic spinning of micro- and nano-scale fibers for tissue engineering. , 2014, Lab on a chip.

[54]  Sze Yi Mak,et al.  The dripping-to-jetting transition in a co-axial flow of aqueous two-phase systems with low interfacial tension , 2017 .

[55]  Xingyu Jiang,et al.  Modular microfluidics for gradient generation. , 2008, Lab on a chip.

[56]  Mark A. Skylar-Scott,et al.  Three-dimensional bioprinting of thick vascularized tissues , 2016, Proceedings of the National Academy of Sciences.

[57]  Lei Wei,et al.  Controlled fragmentation of multimaterial fibres and films via polymer cold-drawing , 2016, Nature.

[58]  Yuanjin Zhao,et al.  Microfluidic Generation of Porous Microcarriers for Three-Dimensional Cell Culture. , 2015, ACS applied materials & interfaces.

[59]  Daniel T Chiu,et al.  Disposable microfluidic substrates: transitioning from the research laboratory into the clinic. , 2011, Lab on a chip.

[60]  Shoji Takeuchi,et al.  Cell-laden microfibers for bottom-up tissue engineering. , 2015, Drug discovery today.

[61]  Shoji Takeuchi,et al.  Metre-long cell-laden microfibres exhibit tissue morphologies and functions. , 2013, Nature materials.

[62]  J. Miao,et al.  A practical guide for the fabrication of microfluidic devices using glass and silicon. , 2012, Biomicrofluidics.

[63]  Xingyu Jiang,et al.  A strategy for rapid and facile fabrication of controlled, layered blood vessel-like structures , 2016 .

[64]  Hua Xu,et al.  Bio-inspired stimuli-responsive graphene oxide fibers from microfluidics , 2017 .

[65]  Albert Folch,et al.  3D-Printed Microfluidics. , 2016, Angewandte Chemie.

[66]  G. Whitesides,et al.  Fabrication of microfluidic systems in poly(dimethylsiloxane) , 2000, Electrophoresis.

[67]  K. Reis,et al.  Advantages and challenges offered by biofunctional core-shell fiber systems for tissue engineering and drug delivery. , 2016, Drug discovery today.

[68]  D. Harris,et al.  How boundaries shape chemical delivery in microfluidics , 2016, Science.

[69]  F. Pampaloni,et al.  The third dimension bridges the gap between cell culture and live tissue , 2007, Nature Reviews Molecular Cell Biology.

[70]  Jesper Gantelius,et al.  3D Bioprinting of Tissue/Organ Models. , 2016, Angewandte Chemie.

[71]  F. Rong,et al.  Double emulsions from a capillary array injection microfluidic device. , 2014, Lab on a chip.

[72]  G. Whitesides The origins and the future of microfluidics , 2006, Nature.

[73]  D. Weitz,et al.  Versatile, cell and chip friendly method to gel alginate in microfluidic devices. , 2016, Lab on a chip.

[74]  Yuanjin Zhao,et al.  Bioinspired Multifunctional Spindle-Knotted Microfibers from Microfluidics. , 2017, Small.

[75]  Jong-Man Kim,et al.  Size-Controlled Fabrication of Polyaniline Microfibers Based on 3D Hydrodynamic Focusing Approach. , 2015, Macromolecular rapid communications.

[76]  C. Liu,et al.  Recent Developments in Polymer MEMS , 2007 .

[77]  Armand Ajdari,et al.  Stability of a jet in confined pressure-driven biphasic flows at low reynolds numbers. , 2007, Physical review letters.

[78]  Yanhui Zhao,et al.  Microfluidic Hydrodynamic Focusing for Synthesis of Nanomaterials. , 2016, Nano today.

[79]  S. Bersini,et al.  Rational Design of Prevascularized Large 3D Tissue Constructs Using Computational Simulations and Biofabrication of Geometrically Controlled Microvessels , 2016, Advanced healthcare materials.

[80]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.