Microcapsules with a permeable hydrogel shell and an aqueous core continuously produced in a 3D microdevice by all-aqueous microfluidics

Mytnyk, Serhii; Ziemecka, Iwona; Olive, Alexandre G. L.; Meer, J.W.M. van der; Totlani, Kartik; Oldenhof, Sander; Kreutzer, Michiel T.; Steijn, Volkert van; Esch, Jan H. van

doi:10.1039/c7ra00452d

Cited by 49 publications

(40 citation statements)

References 40 publications

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“…All‐aqueous emulsions, also called aqueous two‐phase system (ATPS), are immiscible aqueous phases generated by physical LLPS in aqueous polymer solutions . This emulsion system consists of droplets of one aqueous phase dispersed into the other aqueous phase.…”

Section: All‐aqueous Emulsions: Learning From Intracellular Llpsmentioning

confidence: 99%

“…Inspired from the lipid bilayer of cell membrane, interfaces of all‐aqueous emulsions have been employed as 2D templates for fabrication of vesicles composed of a few macromolecular layers, including liposomes, polymersomes, and colloidosomes . Compared to the water–oil interface, the dynamic aqueous–aqueous interface has an ultralow interfacial tension, which gives rise to challenges and opportunities in macromolecular assembly at liquid–liquid interface .…”

Section: All‐aqueous Interface Templated Biomaterials: Assembly Of Armentioning

confidence: 99%

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Cell‐Inspired All‐Aqueous Microfluidics: From Intracellular Liquid–Liquid Phase Separation toward Advanced Biomaterials

et al. 2020

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Living cells have evolved over billions of years to develop structural and functional complexity with numerous intracellular compartments that are formed due to liquid–liquid phase separation (LLPS). Discovery of the amazing and vital roles of cells in life has sparked tremendous efforts to investigate and replicate the intracellular LLPS. Among them, all‐aqueous emulsions are a minimalistic liquid model that recapitulates the structural and functional features of membraneless organelles and protocells. Here, an emerging all‐aqueous microfluidic technology derived from micrometer‐scaled manipulation of LLPS is presented; the technology enables the state‐of‐art design of advanced biomaterials with exquisite structural proficiency and diversified biological functions. Moreover, a variety of emerging biomedical applications, including encapsulation and delivery of bioactive gradients, fabrication of artificial membraneless organelles, as well as printing and assembly of predesigned cell patterns and living tissues, are inspired by their cellular counterparts. Finally, the challenges and perspectives for further advancing the cell‐inspired all‐aqueous microfluidics toward a more powerful and versatile platform are discussed, particularly regarding new opportunities in multidisciplinary fundamental research and biomedical applications.

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Section: All‐aqueous Emulsions: Learning From Intracellular Llpsmentioning

confidence: 99%

Section: All‐aqueous Interface Templated Biomaterials: Assembly Of Armentioning

confidence: 99%

Cell‐Inspired All‐Aqueous Microfluidics: From Intracellular Liquid–Liquid Phase Separation toward Advanced Biomaterials

et al. 2020

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“…These results indicated that at low concentrations (5% (w/w)) of both DEX and PEG, it was difficult to generate droplets. However, when the concentrations of two solutions were increased to 10% (w/w), stable droplets were started to form even with lower molecule weight, compared to existing literature . Moreover, monodispersed droplets were easier to be generated when the concentrations of DEX and PEG were increased to more than 10% (w/w).…”

Section: Resultsmentioning

confidence: 69%

“…So far, two types of strategies are applied to obtain W/W droplets in microfluidic systems. One strategy is to use traditional flow focusing microfluidic device for droplets generation via a passive mode, but it cannot precisely control the size and morphology of W/W droplets. Another one is to generate droplets with external forcing on microfluidic chip, such as electrosprayed emulsion and periodic pulsating inlet pressures, but it is limited by the lower controllability and reproducibility resulting from the relative position variations of these external forces and microfluidic chip.…”

Section: Introductionmentioning

confidence: 99%

A Microfluidic Strategy for Controllable Generation of Water‐in‐Water Droplets as Biocompatible Microcarriers

Liu

Wang

Wei

et al. 2018

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Droplet microfluidics has been widely applied in functional microparticles fabricating, tissue engineering, and drug screening due to its high throughput and great controllability. However, most of the current droplet microfluidics are dependent on water-in-oil (W/O) systems, which involve organic reagents, thus limiting their broader biological applications. In this work, a new microfluidic strategy is described for controllable and high-throughput generation of monodispersed water-in-water (W/W) droplets. Solutions of polyethylene glycol and dextran are used as continuous and dispersed phases, respectively, without any organic reagents or surfactants. The size of W/W droplets can be precisely adjusted by changing the flow rate of dispersed and continuous phases and the valve switch cycle. In addition, uniform cell-laden microgels are fabricated by introducing the alginate component and rat pancreatic islet (β-TC6) cell suspension to the dispersed phase. The encapsulated islet cells retain high viability and the function of insulin secretion after cultivation for 7 days. The high-throughput droplet microfluidic system with high biocompatibility is stable, controllable, and flexible, which can boost various chemical and biological applications, such as bio-oriented microparticles synthesizing, microcarriers fabricating, tissue engineering, etc.

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“…[1] Biocompatible hydrogel microparticles have been previously produced using such methods as electrohydrodynamic jetting, [2] micromolding, [3] and microfluidics. [4] Among them, microfluidics is one of the most promising methods as it allows generation of multi-compartmentalized microparticles with precise control of dimensions and morphologies, [5] such as Janus-type, [6] coreshell, [7] and so-called "crescent-shaped" particles,that possess open cavities. [8] There have been attempts to use the crescentshaped microgels for confining enzymatic reactions for particle propulsion, [9] or for selective capture microscale objects,s uch as smaller particles or algae cells.…”

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confidence: 99%

Self‐Orienting Hydrogel Micro‐Buckets as Novel Cell Carriers

et al. 2018

Self Cite

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Hydrogel microparticles are important in materials engineering, but their applications remain limited owing to the difficulties associated with their manipulation. Herein, we report the self‐orientation of crescent‐shaped hydrogel microparticles and elucidate its mechanism. Additionally, the microparticles were used, for the first time, as micro‐buckets to carry living cells. In aqueous solution, the microparticles spontaneously rotated to a preferred orientation with the cavity facing up. We developed a geometric model that explains the self‐orienting behavior of crescent‐shaped particles by minimizing the potential energy of this specific morphology. Finally, we selectively modified the particles’ cavities with RGD peptide and exploited their preferred orientation to load them with living cells. Cells could adhere, proliferate, and be transported and released in vitro. These micro‐buckets hold a great potential for applications in smart materials, cell therapy, and biological engineering.

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Microcapsules with a permeable hydrogel shell and an aqueous core continuously produced in a 3D microdevice by all-aqueous microfluidics

Abstract: We report the continuous production of microcapsules composed of an aqueous core and permeable hydrogel shell, made stable by the controlled photo-cross-linking of the shell of an all-aqueous double emulsion.

Cited by 49 publications

References 40 publications

Cell‐Inspired All‐Aqueous Microfluidics: From Intracellular Liquid–Liquid Phase Separation toward Advanced Biomaterials

Cell‐Inspired All‐Aqueous Microfluidics: From Intracellular Liquid–Liquid Phase Separation toward Advanced Biomaterials

A Microfluidic Strategy for Controllable Generation of Water‐in‐Water Droplets as Biocompatible Microcarriers

Self‐Orienting Hydrogel Micro‐Buckets as Novel Cell Carriers

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