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

development. Molley et al. directly inscribed the microgels with opposite charges. The additional interacting
vascular system channels and tumor cell aggregates in forces enhance the mechanical properties and self-healing
a microgel matrix containing cells, creating a tumor ability of the microgel. In addition to charge interaction,
microenvironment model [147] . More importantly, this common mechanisms of interparticle interaction include
microgel 3D printing approach is almost applicable to all covalent interaction, adhesive and additive, coordination
types of cell integration [147] . interaction, and interpenetrating network and other
supramolecular interactions. Feng et al. utilized dynamic
7. Summary and outlooks crosslinking to replace the simple accumulation of
microparticle microgel, thereby enhancing the porosity,
The past decades have seen the rapid progression of 3D adhesiveness, and self-healing properties of the resulting
bioprinting from concept validation to in vivo printing microparticle gel . Microgels can be assembled through
[28]
of corresponding structures. However, strategies for various forms of interparticle interaction forces, and the
3D bioprinting are still in the exploratory stages of assembly strategies used can be employed individually
development, with many different strategies being tested, or in combination, making the design of microgel more
evaluated, refined, and integrated. The full clinical diversified and more adaptable to diverse 3D bioprinting
translation of bioprinted tissues and organs is highly applications.
challenging and may take a significant amount of time Porosity is one of the important characteristics of
before 3D bioprinting can be fully utilized for organ microgel, and multiple studies have found that its porosity
transplantation or reconstruction of damaged tissues not only affects the mechanical properties of microgel,
such as blood vessels, nerves, and cartilage. There are still but also affects cell infiltration and migration. Therefore,
many challenges to be addressed in achieving full clinical the optimal porosity of microgel is a focus of concern
translation of 3D bioprinting, but in recent years, microgel for many researchers [149] . Seymour et al. demonstrated
have shown great potential as a bioink for 3D bioprinting.
a simple and easy-to-use method for controlling pore
Microgels are a class of novel biomaterials that size in hydrogels . By crosslinking a mixture of gelatin
[89]
possess numerous advantageous characteristics. As a and GelMA micromicrogel, the pore size of the resulting
bioink, microgel is typically formed by assembling water- GelMA hydrogel can be controlled by removing the
based microgel into a 3D printable medium material gelatin micromicrogel. Hydrogels with different pore sizes
through various assembly methods [66,148] . The most exhibit different properties . The use of a combination
[89]
common method of assembly is achieved through the of various types of microgel–microgel to control pore size
accumulation of microgel–microgel, which in theory, is a widely utilized strategy, but it has proven difficult to
accumulate randomly to form a microgel with a degree develop a comprehensive theoretical system for guiding
of accumulation known as the accumulation fraction. the creation of microgel with controllable pore size. In
Microgels with an accumulation fraction greater than 0.58 response to this challenge, mathematicians and engineers
exhibit a “jamming” state due to the interactions between have studied specific algorithms to calculate and analyze
the microgel–microgel, which grants them unique physical the pore space between stacked microgel, continuously
characteristics such as self-assembly, shear thinning, and optimizing the algorithms through comparison and
self-healing. Therefore, microgel in a “jamming” state analysis of simulated and actual results. While progress
are highly performing bioinks with micron-level pores has been made, this research offers a new approach for
for cell loading and maintenance of cell viability, as well future control of pore size in microgel [150-152] . In addition to
as with good shear thinning properties for printing. The studying the preparation of controllable pore size microgel,
“jamming” microgel is essentially a dynamic scaffold, in the preparation of inhomogeneous pore size asymmetrical
which the interstitial space between accumulated microgel microgel is also a research direction that deserves our
often forms a 3D, interconnected porous network. Cells attention. For example, microgel with inhomogeneous
can freely migrate through this network and engage in and shape-variable pore sizes can be produced through
biological information transfer, which is one of the major mechanical breaking methods. Using this method, bioinks
advantages over traditional hydrogels. The pore size of in special shapes such as “microchains” can be produced,
traditional hydrogels is in the nanometer range, which is which possess characteristics such as high porosity, large
not suitable for cell growth and communication. pore size, and high strength, and hold great potential in
[97]
In addition to the assembly method of gravity-induced bone repair .
accumulation that causes “jamming” of microgel, microgel In addition to the conventional use of microgels as
can also be assembled through other means, such as the bioinks, the 3D bioprinting strategy of using microgels as
assembly of microgel through the interaction of two support baths can also produce products with complex 3D

Volume 9 Issue 5 (2023) 102 https://doi.org/10.18063/ijb.753