Page 105 - IJB-9-5

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

Figure 5. Dynamic crosslinked assembly of microgels as bioinks. (A) Preparation of DC-MA bioink including microfluidic generation of microgels and
assembling microgels via dynamic crosslinker. (B) Properties of DC-MA bioink include (I) printability, (II) tissue adhesion, (III) microporosity, and
(IV) self-healing. (C) Adhesion of DC-MA to tissues and organs such as pig skin, rabbit bone, mouse lung, mouse liver, mouse heart, and mouse kidney.
(D) Maximum tensile stress of pig skins bonded by DC-MA. (E) Self-healing of DC-MA rods. Reprinted with permission from Feng Q, Li D, Li Q, et al.,
2022, Assembling microgels via dynamic cross-linking reaction improves printability, microporosity, tissue-adhesion, and self-healing of microgel bioink
for extrusion bioprinting. ACS Appl Mater Interfaces, 14:15653–15666. Copyright 2022 American Chemical Society [113] .

pore microgel through mechanical fracture (Figure 4D). to undergo continuous stretching, resulting in relatively
[99]
First, the HA-MA hydrogel is mechanically fractured thicker and rougher strands upon extrusion . Reducing
through a sieve with a pore size of 40–100 µm. This the size of the microgel and increasing its mechanical
process deconstructs the hydrogel into microchains, modulus can improve its printability and shape fidelity,
which randomly intertwine with each other to form a high but this is detrimental to the encapsulation of cells and
aspect ratio microgel. This type of microgel is more stable the maintenance of their viability after encapsulation [67,106] .
than particle-like microgel, and can maintain its shape in Additionally, the weak physical interactions between
aqueous media for 7 days without undergoing secondary microgel often require a second crosslinking after extrusion
crosslinking. Through shear recovery testing, it was found in order to enhance the mechanical stability of the printed
that microgels of various sizes have printability. This 3D structure, which can potentially further compromise
strategy was tested by printing a 3D model of a human ear the viability of cells [26,57,95] . To address this challenge,
for half of its size. The printed product had a stable structure, dynamic hydrogel systems based on external stimuli such
and no flowing liquid was observed. Using microgel with a as hydrolysis, locally produced enzymes, and light have
size of 40 μm, cell compatibility was tested, and the results been developed to regulate degradation [107,108] . The main
showed that the cell viability before printing, on the 1st types of bioinks include dynamic covalent bioinks and
day, 7th day, and 21st day were 95.3 ± 0.5%, 90.1 ± 0.6%, supramolecular bioinks [109,110] .
[97]
92.3 ± 1.1%, and 92.6 ± 2%, respectively . One promising solution for enhancing the intermolecular
The use of irregular microgels in bioink formulations can interactions of microgel while still maintaining their
provide several advantages, such as enhanced printability, shear-thinning properties is the establishment of dynamic
cell viability, and biofunctionality. Moreover, the complex covalent bonds between microgel [111,112] .When subjected to
geometries and tunable mechanical properties of irregular external force, dynamic covalent bonds are significantly
microgels can better mimic the native extracellular matrix disrupted, giving the microgel-based bioink good shear
(ECM) in various tissues, which could ultimately promote thinning properties. Upon reduction of external force, the
tissue regeneration and repair. dynamic covalent bonds quickly recover, conferring the
microgel-based bioink excellent self-healing properties
5.2. Improvement of microgel crosslinking methods and mechanical strength. Feng et al. prepared a dynamic
Despite the ease of achieving shear-thinning and cell- crosslinked microgel, which was synthesized from the
encapsulating properties using microgels in direct bioink crosslinking of transparent hyaluronic acid (HAMA-PBA)
writing, there still exist some issues in the printing modified with methacrylate and phenyl boronic acid and
process that need to be addressed. For example, due to GelMA through a microfluidic device, and assembled
the microparticulate nature of microgel and their weak into DC-MA bioink (Figure 5A) [113] . The DC-MA bioink
intermolecular interactions, microgel bioink is unable was obtained by adding HA-DA in the microgel, forming

Volume 9 Issue 5 (2023) 97 https://doi.org/10.18063/ijb.753