Microfluidic Encapsulation of Cells in Polymer Microgels

Velasco, Diego; Tumarkin, Ethan; Kumacheva, Eugenia

doi:10.1002/smll.201102464

Cited by 244 publications

(245 citation statements)

References 69 publications

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“…This droplet-based method is rapid and high throughput. Velasco et al [123] demonstrated that cell-loaded hydrogel droplets significantly reduced the intensive labour needed to fabricate MCSs. In the porous micro droplets, oxygen and nutrients were diffused in and metabolic waste diffused out to maximize the cell viability [124].…”

Section: Micro-droplets-based Multicellular Spheroid Formationmentioning

confidence: 99%

Advances in multicellular spheroids formation

Cui¹,

Hartanto²,

Zhang³

2017

J. R. Soc. Interface.

393

336

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Three-dimensional multicellular spheroids (MCSs) have a complex architectural structure, dynamic cell -cell/cell -matrix interactions and bio-mimicking in vivo microenvironment. As a fundamental building block for tissue reconstruction, MCSs have emerged as a powerful tool to narrow down the gap between the in vitro and in vivo model. In this review paper, we discussed the structure and biology of MCSs and detailed fabricating methods. Among these methods, the approach in microfluidics with hydrogel support for MCS formation is promising because it allows essential cell -cell/cell -matrix interactions in a confined space.

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Section: Micro-droplets-based Multicellular Spheroid Formationmentioning

confidence: 99%

Advances in multicellular spheroids formation

Cui¹,

Hartanto²,

Zhang³

2017

J. R. Soc. Interface.

393

336

View full text Add to dashboard Cite

show abstract

“…The microfluidic technique generated microgels with a 6.22% polydispersity while vortexing produced particle samples with an average polydispersity of 23.62%, Monodispersity of microgels generated by microfluidics has been shown to be increased by further reducing channel and particle size 26 . Well-controlled size distributions holds enabling consequences for precision cell encapsulation 61 and high throughput cell screening 37 .…”

Section: Resultsmentioning

confidence: 99%

A microfluidic-based cell encapsulation platform to achieve high long-term cell viability in photopolymerized PEGNB hydrogel microspheres

et al. 2017

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Cell encapsulation within photopolymerized polyethylene glycol (PEG)-based hydrogel scaffolds has been demonstrated as a robust strategy for cell delivery, tissue engineering, regenerative medicine, and developing in vitro platforms to study cellular behavior and fate. Strategies to achieve spatial and temporal control over PEG hydrogel mechanical properties, chemical functionalization, and cytocompatibility have advanced considerably in recent years. Recent microfluidic technologies have enabled the miniaturization of PEG hydrogels, thus enabling the fabrication of miniaturized cell-laden vehicles. However, rapid oxygen diffusive transport times on the microscale dramatically inhibit chain growth photopolymerization of polyethylene glycol diacrylate (PEGDA), thus decreasing the viability of cells encapsulated within these microstructures. Another promising PEG-based scaffold material, PEG norbornene (PEGNB), is formed by a step-growth photopolymerization and is not inhibited by oxygen. PEGNB has also been shown to be more cytocompatible than PEGDA and allows for orthogonal addition reactions. The step-growth kinetics, however, are slow and therefore challenging to fully polymerize within droplets flowing through microfluidic devices. Here, we describe a microfluidic-based droplet fabrication platform that generates consistently monodisperse cell-laden water-in-oil emulsions. Microfluidically generated PEGNB droplets are collected and photopolymerized under UV exposure in bulk emulsions. In this work, we compare this microfluidic-based cell encapsulation platform with a vortex-based method on the basis of microgel size, uniformity, post-encapsulation cell viability and long-term cell viability. Several factors that influence post-encapsulation cell viability were identified. Finally, long-term cell viability achieved by this platform was compared to a similar cell encapsulation platform using PEGDA. We show that this PEGNB microencapsulation platform is capable of generating cell-laden hydrogel microspheres at high rates with well-controlled size distributions and high long-term cell viability.

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“…Crosslinking PEG-4MAL macromers can be accomplished with dithiol molecules and does not require free radical initiators, which are detrimental to encapsulated cell health 13 . Similar microfluidic schemes for producing microgels [14][15][16] and encapsulating cells [17][18][19] have recently been reported for widely varying applications, including wound healing, stem cell culture and fundamental studies of cell biology. The versatility of microfluidic cell encapsulation extends to other polymers, including Matrigel 20 , agarose 21 and even multilayer core-shell composites such as collagen cores with alginate shells 22 .…”

Section: Introductionmentioning

confidence: 89%

Parallel droplet microfluidics for high throughput cell encapsulation and synthetic microgel generation

2018

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Cells can be microencapsulated in synthetic hydrogel microspheres (microgels) using droplet microfluidics, but microfluidic devices with a single droplet generating geometry have limited throughput, especially as microgel diameter decreases. Here we demonstrate microencapsulation of human mesenchymal stem cells (hMSCs) in small ( o100 μm diameter) microgels utilizing parallel droplet generators on a two-layer elastomer device, which has 600% increased throughput vs. single-nozzle devices. Distribution of microgel diameters were compared between products of parallel vs. single-nozzle configurations for two square nozzle widths, 35 and 100 μm. Microgels produced on parallel nozzles were equivalent to those produced on single nozzles, with substantially the same polydispersity. Microencapsulation of hMSCs was compared for parallel nozzle devices of each width. Thirty five micrometer wide nozzle devices could be operated at twice the cell concentration of 100 μm wide nozzle devices but produced more empty microgels than predicted by a Poisson distribution. Hundred micrometer wide nozzle devices produced microgels as predicted by a Poisson distribution. Polydispersity of microgels did not increase with the addition of cells for either nozzle width. hMSCs encapsulated on 35 μm wide nozzle devices had reduced viability (~70%) and a corresponding decrease in vascular endothelial growth factor (VEGF) secretion compared to hMSCs cultured on tissue culture (TC) plastic. Encapsulating hMSCs using 100 μm wide nozzle devices mitigated loss of viability and function, as measured by VEGF secretion.

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Microfluidic Encapsulation of Cells in Polymer Microgels

Cited by 244 publications

References 69 publications

Advances in multicellular spheroids formation

Advances in multicellular spheroids formation

A microfluidic-based cell encapsulation platform to achieve high long-term cell viability in photopolymerized PEGNB hydrogel microspheres

Parallel droplet microfluidics for high throughput cell encapsulation and synthetic microgel generation

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