Page 106 - IJB-9-5

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

dynamic phenyl boronate bonds between the microgel, alginate hydrogels or other complex substitute materials,
which improved the printing properties and shape fidelity thus presenting certain limitations [117] .
of the DC-MA bioink without sacrificing the encapsulated To overcome these issues, a new strategy method has
cell viability, and did not require secondary crosslinking to recently been proposed, utilizing high-volume-fraction soft
stabilize the printed 3D structure (Figure 5B). According to microgel or colloids (such as microgel) as the coagulation
the experimental data analysis, the storage modulus of the baths or support baths. Due to the rheological properties
microgel bioplastic ink (325 Pa) is significantly lower than of the microgel, they will fluidize at the injection point and
that of the DC-MA bioplastic ink (1926 Pa). The viscosity then rapidly solidify [122] . Compaan et al. prepared microgel
of the DC-MA bioplastic ink (56,210 Pa·s) at zero shear rate of Gellan hydrogel through mechanical breaking method,
is higher than that of the microgel bioplastic ink (22,650 which resulted in irregular microgel and aggregates with
Pa·s). Additionally, the DC-MA bioplastic ink exhibits an average diameter of 50 ± 34 µm [123] . Similarly, 5% and
stronger adhesion properties, with a maximum viscosity 10% agarose were transformed into microgel through
of 83,000 Pa·s compared to the microgel bioplastic ink’s transglutaminase crosslinking, resulting in particle
maximum viscosity of only 19,000 Pa·s. As a result, this diameters of 260 ± 200 µm and 125 ± 100 µm, respectively.
class of microgel readily adheres to tissue and possesses a These were used as Gellan hydrogel–agarose and agarose–
formidable ability for self-healing (Figure 5C–E) [113] . agarose matrices for 3D bioprinting as solidification baths
The extracellular matrix (ECM) is a complex mixture (support baths), with 2% alginate PBS solution used as
of proteins, polysaccharides, and their combination, which the extruded ink. The specific printing pattern is shown
interact through noncovalent interactions to provide in Figure 6A. Prior to printing, the support baths were
temporal and spatial control of the cellular environment crosslinked and had a total polymer concentration range of
and response. Supramolecular bioink utilizes the self- 3.5%–13% w/v. A lower concentration of polymer network
assembly of microgels through the reproduction of such is beneficial for material exchange while still maintaining
noncovalent interactions. Additionally, supramolecular mechanical strength, as data from this study showed
bioink often has self-healing, shear thinning, stress that the effective stiffness of the composite materials of
relaxation, strain hardening, and stimulus response agarose (3%)–gellan (0.5%), agarose (3%)–agarose (5%),
properties [109,114-116] . and agarose (3%)–agarose (10%) were 14.9, 14.4, and
36.3 kPa, respectively. The microgel support bath exhibits
5.3. Improvement of microgel printing methods solid behavior when stationary, but becomes liquid at the
One strategy for 3D bioprinting involves extruding injection site during printing and subsequently solidifies
liquid biomaterials in coagulation baths or support baths, to form channels. In addition to creating channels, this
which function as coagulation baths to rapidly gel the strategy allows for the printing of 3D solid objects, as
biomaterials [117] . Coagulation baths typically consist of shown in Figure 6B, which can rapidly transform any 3D
a liquid that triggers physical or chemical crosslinking shape from a computer model into a solid hydrogel object,
of bioink [118,119] . For example, the use of bioink based on making complex printing more straightforward [123] .
alginate for 3D printing involves depositing the bioink in
a calcium chloride solution to promote ionic crosslinking Bhattacharjee et al. utilized this microgel-based 3D
of the alginate-containing bioink upon extrusion, resulting printing method to construct a variety of interesting and
in a stable structure. This approach has the advantage elegant 3D patterns, demonstrating the vast potential of the
of separating the rheological properties of the bioink microgel support bath strategy in 3D bioprinting [124] . They
from its printability, expanding the design freedom of first prepared a microgel medium through crosslinked PVA
the bioink [120] . However, this strategy has several major hydrogel and fluorescent colloids, and utilized an injection
drawbacks: (i) coagulation baths can quickly spread within head with an inner diameter of 50 µm for writing to create
the needles of the print port and block the ink outlet; and several complex multi-scale structures (Figure 7A) [124] . The
(ii) issues related to the adhesion of continuous layers, the metabolic needs of cells require dense vascular systems,
buoyancy of deposited fibers, and turbulence generated which pose a significant challenge for 3D bioprinting [125] .
during the printing process often restrict the overall Perhaps, this strategy can be utilized to address this
reproducibility and precision of the printed structure [117,121] . challenge. Dumont et al. constructed a complex tubular
Co-axial wet-spinning can be considered an evolution of structure (Figure 7B) with a stable structure that can adjust
the coagulation bath, in which the bioink and crosslinking the thickness of the tube wall (~200 μm) by increasing the
solution are co-extruded from a single deposition nozzle writing rate . This microgel-based support bath printing
[90]
under laminar flow conditions, ensuring a high degree of strategy eliminates the influence of surface tension, gravity,
reproducibility in the deposition process [101] . However, this and particle diffusion, allowing for the writing of materials
technique almost inevitably requires the use of calcium with unlimited width [126-128] .

Volume 9 Issue 5 (2023) 98 https://doi.org/10.18063/ijb.753