Page 95 - IJB-9-5

International Journal of Bioprinting Application and prospects of 3D printable microgels

Table 1. Comparison of different strategies used to manufacture hydrogel particles
Preparation strategies for HMPs Particle geometry Minimum size range Particle size coefficient of variation Productivity
Batch emulsion Spherical 1–10 μm [161] >10% [37] High
Microfluidic technique Spherical 5–10 μm [162,163] <2% [40] Moderate
Photolithography Controllable geometry <1 μm [164] <3% [165] Low
Electrostatic spraying Spherical 1–10 μm [166] >50% [167] Moderate
Mechanical crushing Irregular shape >20 μm [56] >5% [57] High

proliferation [34-36] . In an alternative strategy, hydrogels can ultimately forming microgels with a production rate that
be fabricated into microspheres of various micron sizes, is 10–100 times faster than the traditional microfluidic
known as microgels. Generally, the strategies for preparing strategies . In addition to air-based microfluidic
[41]
microgels are classified into batch emulsion, microfluidic strategies, the use of multi-array high-throughput
technique, photolithography, electrostatic spraying, and microfluidic chips is also an effective approach to improve
mechanical crushing (Table 1). the production rate of microgels . For example, Chung
[42]
et al. developed a multi-layer integrated microfluidic
2.1. Batch emulsion droplet generator that can produce a large quantity of
The batch emulsion method utilizes an immiscible oil and highly uniform microgels . This strategy allows for
[43]
water gel precursor solution to produce microgel. The precise control of the number of cells in each microgel,
basic process involves the mixing of a water gel solution even down to the single-cell level, by controlling process
(containing an initiator) with oil in a container, and the parameters such as the particle size and density of cells
mixture is mechanically stirred to homogenize the solution in the precursor solution. Additionally, high-throughput
and ultimately produce microgel encapsulated by the oil generation of cell-laden microgels can be achieved
phase. The degree of mixing, duration, and intensity through parallelized channels [44,45] . Furthermore,
of mechanical force all influence the particle size and high-throughput centrifugal microfluidic technique is
dispersion of the microgels. Following the production of another emerging method for mass-producing hydrogel
the microgels, crosslinking is typically performed through microspheres [46,47] . The centrifugal microfluidic device
the use of photopolymerization, after which the oil phase can be easily assembled onto a conventional centrifuge,
is removed through steps such as washing, centrifugation, demonstrating high scalability and suitability for large-
and filtration to obtain usable microgels. Overall, this scale production of hydrogel microspheres .
[48]
microgel production method is simple and efficient, with a
high production rate. However, some of its drawbacks are
the microgels produced having a particle size coefficient 2.3. Photolithography
of variation >10% and the poor dispersion, which can Photolithography techniques can be broadly categorized
[37]
be improved by continuous filtration of a highly disperse into three types: imprint lithography, photolithography,
microgel suspension through a filter, as proposed by and flow lithography. In the imprint lithography
Truong et al., to obtain more monodisperse suspensions . strategy, a hydrogel precursor is loaded into a mold with
[38]
the desired microgel characteristics, and crosslinked,
[49]
2.2. Microfluidic technique followed by solidification . In the photolithography
Microfluidic technique involves guiding the flow of oil process, the precursor solution of hydrogel is selectively
and water phases at a cross junction to achieve controlled solidified by templated photomasks, ultimately resulting
[50]
formation of microgels. Shear force and hydrophobic in the formation of microgel . In the case of flow
interactions induce the formation of water droplets photolithography, the precursor solution of the flowing
within the oil phase . By changing the geometric shape hydrogel is periodically solidified by a light mask, ultimately
[27]
of the intersection and the relative velocities between the resulting in the formation of microgel . The advantage of
[51]
two phases, the diameter of microgels (5–500 μm) can be the photolithography method lies in its ability to precisely
controlled . By maintaining stable relative velocities, control the geometric shape and monodispersity of the
[39]
highly monodisperse microgel suspensions with microgel, but it is limited by the mold and has low yield.
excellent dispersity indices (1%–2%) can be obtained . Currently, several methods have been developed to increase
[40]
One limitation of the microfluidic technique is the low the yield of microgel produced through photolithography
production rate. To address this issue, Kamperman et al. techniques, such as accelerating the curing rate of the
developed an air microfluidic strategy in which two hydrogel precursor, enhancing the intensity of the light
microscale liquid flows are sprayed together and collide, source, or increasing the concentration of initiators [52,53] .

Volume 9 Issue 5 (2023) 87 https://doi.org/10.18063/ijb.753