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Production of hydrogel microparticles in microfluidic devices: a review

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Abstract

Hydrogels are biocompatible materials commonly used in biological applications, such as cell encapsulation, tissue engineering and drug delivery systems. The use of hydrogels in the form of microparticles brings, for several purposes, many advantages, since the particles have a high surface-to-volume ratio and they can be delivered inside microscale structures such as blood microvessels and tissues. Microfluidic devices are a promising approach to produce hydrogel microparticles because they enable a high precision control of the flow streams during the microfabrication process, leading to microparticles with precise size, shape, mechanical properties and cross-linking density. In this review, the focus is put on the most important features to be considered when producing hydrogel microparticles through microfluidic devices. First, the design strategies of microfluidic devices, the selection of the operating conditions and the importance of surfactants are analyzed. Then, the most important gelation mechanisms are reviewed. Afterwards, the most commonly used hydrogel materials are introduced, and their properties are referred. Finally, the different methods to control the size, shape and particle microstructure are discussed and the main challenges for the future are addressed.

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© 2015 WILEY–VCH Verlag GmbH & Co. KGaA, Weinheim

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Abbreviations

PEG:

Poly(ethylene glycol)

PEGDA:

Poly(ethylene glycol) diacrylate

ELPs:

Elastin-like peptides

PEO–PPO–PEO:

Poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide)

PNIPAAM:

Poly(N-isopropyl acrylamide)

PEGMEA:

Poly(ethylene glycol) methyl ether acrylate

CFL:

Continuous flow lithography

PDMS:

Poly(dimethyl siloxane)

SFL:

Stop flow lithography

SFIL:

Stop flow interference lithography

SLMs:

Spatial light modulators

DEP:

Dielectrophoresis

EWOD:

Electrowetting on dielectric

CMC:

Critical micelle concentration

EDS:

Equilibrium droplet size

PVA:

Poly(vinyl alcohol)

HA:

Hyaluronic acid

Cai :

Capillary number of the phase i

μi :

Viscosity of the phase i

v i :

Velocity of the phase i

σ:

Surface tension between the two phases

Rei :

Reynolds number of the phase i

ρi :

Density of the phase i

v i :

Velocity of the phase i

D :

Diameter of the microchannel

φ:

Flow rate ratio

Qd :

Flow rate of the dispersed phase

Qc:

Flow rate of the continuous phase

λ:

Viscosity ratio

μc :

Viscosity of the dispersed phase

μc :

Viscosity of the continuous phase

Wei :

Weber number of the phase i

Cac :

Capillary number of the continuous phase

Cad :

Capillary number of the dispersed phase

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Acknowledgements

This work was funded by FEDER funds through COMPETE2020—Operational Programme for Competitiveness Factors (POCI) and National Funds (PIDDAC) through FCT (Fundação para a Ciência e a Tecnologia) under project POCI-01-0145-FEDER-016861-PTDC/QEQ-FTT/4287/2014, PhD grant PD/BD/114313/2016 and Transport Phenomena Research Center—CEFT base funding UIDB/00532/2020.

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    A. Moreira, J. Carneiro, J. B. L. M. Campos & J. M. Miranda

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Moreira, A., Carneiro, J., Campos, J.B.L.M. et al. Production of hydrogel microparticles in microfluidic devices: a review. Microfluid Nanofluid 25, 10 (2021). https://doi.org/10.1007/s10404-020-02413-8

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